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Sample records for iodine deficiency induces

  1. Iodine Deficiency

    MedlinePlus

    ... enlargement of the thyroid (goiter – see Goiter brochure ), hypothyroidism (see Hypothyroidism brochure ) and to mental retardation in infants and ... when lying down, and difficulty swallowing and breathing. HYPOTHYROIDISM – As the body’s iodine levels fall, hypothyroidism may ...

  2. Hypothyroxinemia induced by maternal mild iodine deficiency impairs hippocampal myelinated growth in lactational rats.

    PubMed

    Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

    2015-11-01

    Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring.

  3. Iodine-deficiency disorders.

    PubMed

    Zimmermann, Michael B; Jooste, Pieter L; Pandav, Chandrakant S

    2008-10-01

    2 billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed iodine-deficiency disorders. Iodine deficiency is the most common cause of preventable mental impairment worldwide. Assessment methods include urinary iodine concentration, goitre, newborn thyroid-stimulating hormone, and blood thyroglobulin. In nearly all countries, the best strategy to control iodine deficiency is iodisation of salt, which is one of the most cost-effective ways to contribute to economic and social development. When iodisation of salt is not possible, iodine supplements can be given to susceptible groups. Introduction of iodised salt to regions of chronic iodine-deficiency disorders might transiently increase the proportion of thyroid disorders, but overall the small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency. International efforts to control iodine-deficiency disorders are slowing, and reaching the third of the worldwide population that remains deficient poses major challenges. PMID:18676011

  4. Health consequences of iodine deficiency.

    PubMed

    Kapil, Umesh

    2007-12-01

    Iodine Deficiency Disorders (IDD) are one of the biggest worldwide public health problem of today. Their effect is hidden and profoundly affects the quality of human life. Iodine deficiency occurs when the soil is poor in iodine, causing a low concentration in food products and insufficient iodine intake in the population. When iodine requirements are not met, the thyroid may no longer be able to synthesize sufficient amounts of thyroid hormone. The resulting low-level of thyroid hormones in the blood is the principal factor responsible for the series of functional and developmental abnormalities, collectively referred to as IDD. Iodine deficiency is a significant cause of mental developmental problems in children, including implications on reproductive functions and lowering of IQ levels in school-aged children. The consequence of iodine deficiency during pregnancy is impaired synthesis of thyroid hormones by the mother and the foetus. An insufficient supply of thyroid hormones to the developing brain may result in mental retardation. Brain damage and irreversible mental retardation are the most important disorders induced by iodine deficiency. Daily consumption of salt fortified with iodine is a proven effective strategy for prevention of IDD. PMID:21748117

  5. [Iodine deficiency during pregnancy ].

    PubMed

    de Luis, D A; Aller, R; Izaola, O

    2005-09-01

    Iodine is an essential micronutrient, it would be administered every day with our diet. The main role of this micronutrient is the synthesis of thyroid hormone. Thyroid hormones are related with brain development and metabolic regulation. Iodine deficit is related with goitre, and an important problem "diseases related with iodine deficiency", including high rate of neonatal mortality, decrease of intelligence, delayed of growth, high rate of aborts and congenital abnormalities.A risk group is pregnant women. Some authors have been demonstrated the utility of iodine supplementation during pregnancy. A systematic review of Cochrane group has shown that iodine supplementation during pregnancy decreased neonatal mortality RR 0.71 (0.56-0.9), and decrease the incidence of cretinism in children under 4 years RR 0.27 (0.12-0.6). As final recommendations, a program in pregnant women must be development to treat with iodine such as we make with folic acid. Pills with iron and iodine (1 mg iron and 25 ug iodine) have been demonstrated better results that pills with iodine. Tablets are the main presentation due to the role of the women in our Society and the work time. Programs of iodine enriched salt have been demonstrated a follow up of 50%. PMID:16386080

  6. Iodine deficiency disorders.

    PubMed

    Elliott, T C

    1987-01-01

    Iodine deficiency disorder (IDD) affects 800 million people in the world, yet iodine supplementation is one of the most cost-effective nutritional interventions known. Iodine is incorporated into thyroid hormones, necessary for regulating metabolic rate, growth, and development of the brain and nervous system. IDD may appear as goiter in adults, usually not a serious problem, or in cretinism in children, which is marked by severe mental and physical retardation, with irreversible hearing and speech defects and either deaf-mutism, squint and paralysis, or stunting and edema. Children supplemented by age 1 or 2 can sometimes be helped. Foods contain variable amounts of iodine dependent on the soil where they are grown, hence mountainous and some inland regions have high goiter and IDD incidence. There are also goitrogenic foods, typically those of the cabbage family. Diagnosis is clinical or by blood tests for thyroid hormone levels and ratios. Finger-stick methods are available. Prevention of IDD is simple with either iodized salt or flour, iodinated central water supplies, injectable or oral iodine-containing oil. All cost about $.04 per person per year, except injections, which cost about $1 per person, but have the advantage that they could be combined with immunizations. Local problems with supplements are loss of iodine in salt with storage in tropics, and local production of cheaper uniodinated salt. Emphasis should be given to pregnant women and young children. There is no harm in giving pregnant women iodine injections in 2nd or 3rd trimester. PMID:12343033

  7. Iodine deficiency and thyroid disorders.

    PubMed

    Zimmermann, Michael B; Boelaert, Kristien

    2015-04-01

    Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders.

  8. Iodine: deficiency and therapeutic considerations.

    PubMed

    Patrick, Lyn

    2008-06-01

    Iodine deficiency is generally recognized as the most commonly preventable cause of mental retardation and the most common cause of endocrinopathy (goiter and primary hypothyroidism). Iodine deficiency becomes particularly critical in pregnancy due to the consequences for neurological damage during fetal development as well as during lactation. The safety of therapeutic doses of iodine above the established safe upper limit of 1 mg is evident in the lack of toxicity in the Japanese population that consumes 25 times the median intake of iodine consumption in the United States. Japan's population suffers no demonstrable increased incidence of autoimmune thyroiditis or hypothyroidism. Studies using 3.0- to 6.0-mg doses to effectively treat fibrocystic breast disease may reveal an important role for iodine in maintaining normal breast tissue architecture and function. Iodine may also have important antioxidant functions in breast tissue and other tissues that concentrate iodine via the sodium iodide symporter. PMID:18590348

  9. Developmental hypothyroxinaemia induced by maternal mild iodine deficiency delays hippocampal axonal growth in the rat offspring.

    PubMed

    Wei, W; Wang, Y; Wang, Y; Dong, J; Min, H; Song, B; Teng, W; Xi, Q; Chen, J

    2013-09-01

    Iodine is essential for the biosynthesis of thyroid hormones, including triiodothyronine and thyroxine. Thyroid hormones are important for central nervous system development. Mild maternal iodine deficiency (ID)-induced hypothyroxinaemia causes neurological deficits and mental retardation of the foetus. However, the detailed mechanism underlying these deficits is still largely unknown. Given that the growth-associated protein of 43 kDa (GAP-43), semaphorin 3A (Sema3A) and the glycogen synthase kinase 3β (GSK3β)/collapsin response mediator protein 2 (CRMP2) pathway are essential for axonal development, we hypothesise that hippocampal axonal growth-related proteins may be impaired, which may contribute to hippocampal axonal growth delay in rat offspring exposed to maternal hypothyroxinaemia. To test this hypothesis, maternal hypothyroxinaemia models were established in Wistar rats using a mild ID diet. Besides a negative control group, two maternal hypothyroidism models were created with either a severe ID diet or methimazole in the water. Our results showed that maternal hypothyroxinaemia exposure delayed offspring axonal growth on gestational day 19, postnatal day (PN) 7, PN14 and PN21. Consistent with this, the mean intensity of hippocampal CRMP2 and Tau1 immunofluorescence axonal protein was reduced in the mild ID group. Moreover, maternal hypothyroxinaemia disrupted expressions of GAP-43 and Sema3A. Furthermore, the phosphorylation of GSK3β and CRMP2 was also affected in the treated offspring, implying a potential mechanism by which hypothyroxinaemia-exposure affects neurodevelopment. Taken together, our data support the hypothesis that maternal hypothyroxinaemia may impair axonal growth of the offspring. PMID:23763342

  10. Developmental hypothyroxinaemia induced by maternal mild iodine deficiency delays hippocampal axonal growth in the rat offspring.

    PubMed

    Wei, W; Wang, Y; Wang, Y; Dong, J; Min, H; Song, B; Teng, W; Xi, Q; Chen, J

    2013-09-01

    Iodine is essential for the biosynthesis of thyroid hormones, including triiodothyronine and thyroxine. Thyroid hormones are important for central nervous system development. Mild maternal iodine deficiency (ID)-induced hypothyroxinaemia causes neurological deficits and mental retardation of the foetus. However, the detailed mechanism underlying these deficits is still largely unknown. Given that the growth-associated protein of 43 kDa (GAP-43), semaphorin 3A (Sema3A) and the glycogen synthase kinase 3β (GSK3β)/collapsin response mediator protein 2 (CRMP2) pathway are essential for axonal development, we hypothesise that hippocampal axonal growth-related proteins may be impaired, which may contribute to hippocampal axonal growth delay in rat offspring exposed to maternal hypothyroxinaemia. To test this hypothesis, maternal hypothyroxinaemia models were established in Wistar rats using a mild ID diet. Besides a negative control group, two maternal hypothyroidism models were created with either a severe ID diet or methimazole in the water. Our results showed that maternal hypothyroxinaemia exposure delayed offspring axonal growth on gestational day 19, postnatal day (PN) 7, PN14 and PN21. Consistent with this, the mean intensity of hippocampal CRMP2 and Tau1 immunofluorescence axonal protein was reduced in the mild ID group. Moreover, maternal hypothyroxinaemia disrupted expressions of GAP-43 and Sema3A. Furthermore, the phosphorylation of GSK3β and CRMP2 was also affected in the treated offspring, implying a potential mechanism by which hypothyroxinaemia-exposure affects neurodevelopment. Taken together, our data support the hypothesis that maternal hypothyroxinaemia may impair axonal growth of the offspring.

  11. [Iodine deficiency in cardiovascular diseases].

    PubMed

    Molnár, I; Magyari, M; Stief, L

    1998-08-30

    The thyroid hormone deficiency on cardiovascular function can be characterized with decreased myocardial contractility and increased peripheral vascular resistance as well as with the changes in lipid metabolism. 42 patients with cardiovascular disease (mean age 65 +/- 13 yr, 16 males) were investigated if iodine insufficiency can play a role as a risk factor for the cardiovascular diseases. The patients were divided in 5 subgroups on the ground of the presence of hypertension, congestive heart failure, cardiomyopathy, coronary disfunction and arrhythmia. Urine iodine concentration (5.29 +/- 4.52 micrograms/dl) was detected with Sandell-Kolthoff colorimetric reaction. The most decreased urine iodine concentration was detected in the subgroups with arrhythmia and congestive heart failure (4.7 +/- 4.94 micrograms/dl and 4.9 +/- 4.81 micrograms/dl, respectively). An elevated TSH level was found by 3 patients (5.3 +/- 1.4 mlU/l). An elevation in lipid metabolism (cholesterol, triglyceride) associated with all subgroups without arrhythmia. In conclusion, the occurrence of iodine deficiency in cardiovascular disease is frequent. Iodine supplementation might prevent the worsing effect of iodine deficiency on cardiovascular disease.

  12. The changing epidemiology of iodine deficiency.

    PubMed

    Li, Mu; Eastman, Creswell J

    2012-07-01

    Globally, about 2 thousand million people are affected by iodine deficiency. Although endemic goitre is the most visible sign of iodine deficiency, its most devastating consequence is brain damage causing mental retardation in children. The relationship between iodine deficiency and brain damage was not clearly established until the 1980s when the term iodine deficiency disorders (IDDs), which encompass a spectrum of conditions caused by iodine deficiency, was introduced. This paradigm shift in the understanding of the clinical consequences of iodine deficiency led to a change in iodine deficiency assessment. The median urinary iodine excretion level has been recommended as the preferred indicator for monitoring population iodine deficiency status since 2001. The 2007 WHO urinary iodine data in schoolchildren from 130 countries revealed that iodine intake is still insufficient in 47 countries. Furthermore, about one-third of countries lack national estimates of the prevalence of iodine deficiency. The picture that has emerged from available data worldwide over the past two decades is that IDDs are not confined to remote, mountainous areas in developing countries, but are a global public health problem that affects most countries, including developed countries and island nations. The recognition of the universality of iodine deficiency highlights the need to develop and apply new strategies to establish and maintain sustainable IDD elimination and strengthen regular monitoring programmes. PMID:22473332

  13. [Iodine deficiency in infancy - a risk for cognitive development].

    PubMed

    Remer, T; Johner, S A; Gärtner, R; Thamm, M; Kriener, E

    2010-08-01

    Severe iodine deficiency during pregnancy seriously influences fetal brain development and in the worst case induces cretinism. Recent studies have shown that even a mild iodine deficiency during pregnancy and during the first years of life adversely affects brain development. The World Health Organisation (WHO) considers iodine deficiency as the most common preventable cause of early childhood mental deficiency. In this context, the insufficient production of the four iodine atoms containing thyroxine seems to play a causal role, i. e., due to the iodine substrate deficiency the neuronally particularly relevant free-thyroxine level falls. Due to the very limited iodine storage capacity, the infantile thyroid is eminently dependent on an adequate and steady iodine supply. In the first month of life, when milk is the only energy- and nutrient provider, infants fed a commercial formula regularly have a sufficient iodine supply. However, breastfed infants, who depend on maternal iodine status, frequently show an inadequate iodine intake. Furthermore, iodine intake is critical when complementary food (CF) is introduced. Especially homemade CF is poor in iodine, but also commercial CFs are only partly fortified. A simultaneous inadequate iodine supply of the breastfeeding mother and the preferential use of mostly iodine-poor organic milk cannot ensure an adequate iodine supply of the infant. In terms of an improvement of nutrient supply, especially concerning an unhindered brain development, the corresponding German reference value for iodine intake of infants until age 4 month should be raised from currently 40 microg/d to at least 60 microg/d (WHO-reference: 90 microg/d). PMID:20665419

  14. Iodine deficiency disorders (IDD) and their eradication.

    PubMed

    Hetzel, B S

    1983-11-12

    Disorders resulting from severe iodine deficiency affect more than 400 million people in Asia alone. These disorders include stillbirths, abortions, and congenital anomalies; endemic cretinism, characterised most commonly by mental deficiency, deaf mutism, and spastic diplegia and lesser degrees of neurological defect related to fetal iodine deficiency; and impaired mental function in children and adults with goitre associated with subnormal concentrations of circulating thyroxine. Use of the term iodine deficiency disorders, instead of "goitre", would help to bridge the serious gap between knowledge and its application. Iodised salt and iodised oil (by injection or by mouth) are suitable for the correction of iodine deficiency on a mass scale. A single dose of iodised oil can correct severe iodine deficiency for 3-5 years. Iodised oil offers a satisfactory immediate measure for primary care services until an iodised salt programme can be implemented. The complete eradication of iodine deficiency is therefore feasible within 5-10 years. PMID:6138653

  15. Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects.

    PubMed

    Vanderpas, J B; Contempré, B; Duale, N L; Deckx, H; Bebe, N; Longombé, A O; Thilly, C H; Diplock, A T; Dumont, J E

    1993-02-01

    Studies were performed to assess the role of combined selenium and iodine deficiency in the etiology of endemic myxedematous cretinism in a population in Zaire. One effect of selenium deficiency may be to lower glutathione peroxidase activity in the thyroid gland, thus allowing hydrogen peroxide produced during thyroid hormone synthesis to be cytotoxic. In selenium-and-iodine-deficient humans, selenium supplementation may aggravate hypothyroidism by stimulating thyroxin metabolism by the selenoenzyme type I iodothyronine 5'-deiodinase. Selenium supplementation is thus not indicated without iodine or thyroid hormone supplementation in cases of combined selenium and iodine deficiencies.

  16. Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects.

    PubMed

    Vanderpas, J B; Contempré, B; Duale, N L; Deckx, H; Bebe, N; Longombé, A O; Thilly, C H; Diplock, A T; Dumont, J E

    1993-02-01

    Studies were performed to assess the role of combined selenium and iodine deficiency in the etiology of endemic myxedematous cretinism in a population in Zaire. One effect of selenium deficiency may be to lower glutathione peroxidase activity in the thyroid gland, thus allowing hydrogen peroxide produced during thyroid hormone synthesis to be cytotoxic. In selenium-and-iodine-deficient humans, selenium supplementation may aggravate hypothyroidism by stimulating thyroxin metabolism by the selenoenzyme type I iodothyronine 5'-deiodinase. Selenium supplementation is thus not indicated without iodine or thyroid hormone supplementation in cases of combined selenium and iodine deficiencies. PMID:8427203

  17. Eliminating iodine deficiency: obstacles and their removal.

    PubMed

    Padilla, Carmencita David; Fagela-Domingo, Carmelita

    2008-12-01

    Iodine deficiency remains a global concern for developing countries and some industrialised countries. Iodine deficiency is the most common cause of preventable mental retardation, posing a threat to the social and economic development of countries. Initiatives were developed and instituted to accelerate progress to achieve the goal of universal salt iodisation (USI). However, these efforts were not successful in eliminating iodine deficiency disorders (IDD) in some countries. Every year, 50 million children are born without the protection that iodine offers to the growing brain and body and about 18 million suffer some significant degree of mental impairment. The World Health Organization (WHO), United Nations Children's Fund (UNICEF) and non-governmental organisations assist to ensure that populations at risk have access to iodised salt. This paper will review the highlights of iodine deficiency and present the experiences in the various countries in Asia, i.e. assessments of the situation, action plans, and obstacles to implementation. PMID:19904447

  18. Acquired hypothyroidism due to iodine deficiency in an American child.

    PubMed

    Brooks, Merrian J; Post, Ernest M

    2014-11-01

    Acquired hypothyroidism secondary to iodine deficiency is rarely reported in iodine-replete environments. The case of a 9-year-old patient with severe acquired hypothyroidism due to iodine deficiency is presented. His deficiency occurred because of a restrictive diet used to control eosinophilic esophagitis. Hypothyroidism and iodine deficiency were quickly corrected with a kelp supplement.

  19. Iodine deficiency in vegetarians and vegans.

    PubMed

    Krajcovicová-Kudlácková, M; Bucková, K; Klimes, I; Seboková, E

    2003-01-01

    Iodine content in food of plant origin is lower in comparison with that of animal origin due to a low iodine concentration in soil. Urinary iodine excretion was assessed in 15 vegans, 31 lacto- and lacto-ovovegetarians and 35 adults on a mixed diet. Iodine excretion was significantly lower in alternative nutrition groups - 172 microg/l in vegetarians and 78 microg/l in vegans compared to 216 microg/l in subjects on a mixed diet. One fourth of the vegetarians and 80% of the vegans suffer from iodine deficiency (iodine excretion value below 100 microg/l) compared to 9% in the persons on a mixed nutrition. The results show that under conditions of alternative nutrition, there is a higher prevalence of iodine deficiency, which might be a consequence of exclusive or prevailing consumption of food of plant origin, no intake of fish and other sea products, as well as reduced iodine intake in the form of sea salt. PMID:12748410

  20. Iodine Deficiency Induces a Thyroid Stimulating Hormone-Independent Early Phase of Microvascular Reshaping in the Thyroid

    PubMed Central

    Gérard, Anne-Catherine; Poncin, Sylvie; Caetano, Bertrand; Sonveaux, Pierre; Audinot, Jean-Nicolas; Feron, Olivier; Colin, Ides M.; Soncin, Fabrice

    2008-01-01

    Expansion of the thyroid microvasculature is the earliest event during goiter formation, always occurring before thyrocyte proliferation; however, the precise mechanisms governing this physiological angiogenesis are not well understood. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry to measure gene expression and laser Doppler to measure blood flow in an animal model of goitrogenesis, we show that thyroid angiogenesis occurred into two successive phases. The first phase lasted a week and involved vascular activation; this process was thyroid-stimulating hormone (TSH)-independent and was directly triggered by expression of vascular endothelial growth factor (VEGF) by thyrocytes as soon as the intracellular iodine content decreased. This early reaction was followed by an increase in thyroid blood flow and endothelial cell proliferation, both of which were mediated by VEGF and inhibited by VEGF-blocking antibodies. The second, angiogenic, phase was TSH-dependent and was activated as TSH levels increased. This phase involved substantial up-regulation of the major proangiogenic factors VEGF-A, fibroblast growth factor-2, angiopoietin 1, and NG2 as well as their receptors Flk-1/VEGFR2, Flt-1/VEGFR1, and Tie-2. In conclusion, goiter-associated angiogenesis promotes thyroid adaptation to iodine deficiency. Specifically, as soon as the iodine supply is limited, thyrocytes produce proangiogenic signals that elicit early TSH-independent microvascular activation; if iodine deficiency persists, TSH plasma levels increase, triggering the second angiogenic phase that supports thyrocyte proliferation. PMID:18276786

  1. Iodine-Induced hypothyroidism.

    PubMed

    Markou, K; Georgopoulos, N; Kyriazopoulou, V; Vagenakis, A G

    2001-05-01

    Iodine is an essential element for thyroid hormone synthesis. The thyroid gland has the capacity and holds the machinery to handle the iodine efficiently when the availability of iodine becomes scarce, as well as when iodine is available in excessive quantities. The latter situation is handled by the thyroid by acutely inhibiting the organification of iodine, the so-called acute Wolff-Chaikoff effect, by a mechanism not well understood 52 years after the original description. It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The Wolff-Chaikoff effect is an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones. The acute Wolff-Chaikoff effect lasts for few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns. This is achieved by decreasing the intrathyroidal inorganic iodine concentration by down regulation of the sodium iodine symporter (NIS) and therefore permits the TPO-H202 system to resume normal activity. However, in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues. Iodide-induced hypothyroidism has also been observed in patients with a history of postpartum thyroiditis, in euthyroid patients after a previous episode of subacute thyroiditis, and in patients treated with recombinant interferon-alpha who developed transient thyroid dysfunction during interferon-a treatment. The

  2. Iodine deficiency in Europe and its consequences: an update.

    PubMed

    Delange, François

    2002-08-01

    This paper updates the information on the prevalence of the disorders induced by iodine deficiency (IDD) in Europe. Thirty-two European countries were still affected by mild to severe iodine deficiency in the late 1990s. The most severely affected countries were in Eastern Europe, including Central Asia, but Western Europe was also still affected. National surveys recently conducted in 11 of these countries show that, with the exception of the Netherlands, none has yet reached a state of iodine sufficiency, though very significant improvement in the situation has been evidenced in many of them, e.g. Poland, Bulgaria and Macedonia. The consequences of persisting iodine deficiency are goitre, hyperavidity of the thyroid for iodide (which increases the risk of thyroid irradiation in the event of a nuclear accident) and subclinical hypothyroidism during pregnancy and early infant (with a concomitant risk of minor brain damage and irreversible impairment of the neuropsychointellectual development of offspring). Access to iodised salt at the household level in European countries affected by IDD increased from 5%-10% in 1990 to 28% in 1999. This constitutes encouraging progress. However, in terms of access of iodine-deficient countries to iodised salt, Europe remains the worst region in the world, as shown by the fact that the mean figure worldwide in 1999 was 68%. In Latin America it even reached 90%. Salt iodisation has to be further implemented in Europe. Until that goal is achieved, iodine supplementation in those groups most sensitive to the effects of iodine deficiency (pregnant and lactating women and young infants) will have to be considered in the most severely affected areas. PMID:12192540

  3. Iodine requirements and the risks and benefits of correcting iodine deficiency in populations.

    PubMed

    Zimmermann, Michael B

    2008-01-01

    Iodine deficiency has multiple adverse effects on growth and development due to inadequate thyroid hormone production that are termed the iodine deficiency disorders (IDD). IDD remains the most common cause of preventable mental impairment worldwide. IDD assessment methods include urinary iodine concentration, goiter, thyroglobulin and newborn thyrotropin. In nearly all iodine-deficient countries, the best strategy to control IDD is salt iodization, one of the most cost-effective ways to contribute to economic and social development. When salt iodization is not possible, iodine supplements can be targeted to vulnerable groups. Introduction of iodized salt to regions of chronic IDD may transiently increase the incidence of thyroid disorders, and programs should include monitoring for both iodine deficiency and excess. Although more data on the epidemiology of thyroid disorders caused by differences in iodine intake are needed, overall, the relatively small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency. PMID:18565420

  4. Iodine Deficiency in School Children in Aligarh District, India.

    PubMed

    Aslami, Ahmad Nadeem; Ansari, Mohammed A; Khalique, N; Kapil, Umesh

    2016-08-01

    We carried out this study to assess iodine deficiency disorders among school children of 6-12 years age group in Aligarh district of India. The prevalence of goiter was 5.2%. Median Urinary Iodine Excretion level was 150 ug/L; 22.5% of students had biochemical iodine deficiency. 50.4% households were consuming adequately iodized salt. PMID:27567653

  5. A comparative study on the effects of excess iodine and herbs with excess iodine on thyroid oxidative stress in iodine-deficient rats.

    PubMed

    Gao, Tianshu; Shi, Rui; Qi, Tengche; Yin, Huisi; Mei, Lan; Han, Xiaoqing; Cui, Peng

    2014-02-01

    This study aimed to compare the effect of excess iodine and herbs with excess iodine on treating iodine deficiency-induced goiter from the perspective of oxidative stress and to measure selenium values in Chinese herbs. One hundred twenty 4-week-old Wistar rats were selected and randomly divided into four groups after inducing iodine-deficiency goiter: normal control group (NC), model control group (MC), iodine excess group (IE), and herbs with iodine excess group (HIE). The activities of oxidative enzymes and levels of oxidative products were measured using biochemical tests. The expression of 4-hydroxynonenal (4-HNE) in the thyroid was detected by immunohistochemistry and the expression of peroxiredoxin 5 (PRDX5) by the Western blot and immunohistochemistry. Selenium values in iodine-excessive herbs were measured by hydride generation-atomic fluorescence spectrometry. The herbs with iodine excess were tested to contain rich selenium. The activities of superoxide dismutase (SOD) and PRDX5 increased markedly, and the values of malondialdehyde (MDA) and 4-HNE decreased significantly in the HIE group. In conclusion, compared with excess iodine, herbs with excess iodine damaged thyroid follicular cells less, which may be related to the increase of antioxidant capacity and rich selenium values in iodine-excessive herbs.

  6. Developmental hypothyroxinemia caused by mild iodine deficiency leads to HFS-induced LTD in rat hippocampal CA1 region: involvement of AMPA receptor.

    PubMed

    Wang, Yi; Wei, Wei; Song, Binbin; Wang, Yuan; Dong, Jing; Min, Hui; Chen, Jie

    2014-10-01

    Hypothyroidism induced by severe iodine deficiency (ID) during developmental period seriously damages the central nervous system function. In addition to developmental hypothyroidism induced by severe ID, developmental hypothyroxinemia induced by mild ID is potentially damaging for neurodevelopment and learning and memory in children. Wistar rats were treated with iodine-deficient diet or methimazole (MMZ) during pregnancy and lactation to induce developmental hypothyroxinemia or hypothyroidism in the present study. Pups were weaned on postnatal day (PN) 21 and used for electrophysiological recordings on PN80. It is generally accepted that long-term depression (LTD) is induced at low-frequency stimulation (LFS) in hippocampal CA1 region. Surprisingly, we observed developmental hypothyroxinemia as well as developmental hypothyroidism led to high-frequency stimulation (HFS)-induced LTD in hippocampal CA1 region. The abnormal HFS-induced LTD suggests not only developmental hypothyroidism but also developmental hypothyroxinemia impairs learning and memory. To explore the mechanisms responsible for the HFS-induced LTD, the phosphorylation status of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) was investigated. The results showed that developmental hypothyroxinemia as well as developmental hypothyroidism decreased the phosphorylation of AMPAR subunit glutamate receptor 1 (GluR1) at serine 831 and serine 845 in hippocampal CA1 region. Neither developmental hypothyroxinemia nor developmental hypothyroidism altered the phosphorylation of AMPAR subunit glutamate receptor 2 (GluR2) at serine 880. Increased levels of protein phosphatase-1 (PP1) were also observed in hippocampal CA1 regions of pups subjected to developmental hypothyroxinemia or hypothyroidism. Taken together, our results suggest that the increased levels of PP1 caused by developmental hypothyroxinemia or hypothyroidism may account for the dephosphorylation of GluR1 at serine 831 and

  7. Iodine deficiency disorders (IDD) control in India

    PubMed Central

    Pandav, Chandrakant S.; Yadav, Kapil; Srivastava, Rahul; Pandav, Rijuta; Karmarkar, M.G.

    2013-01-01

    Iodine deficiency disorders (IDD) constitute the single largest cause of preventable brain damage worldwide. Majority of consequences of IDD are invisible and irreversible but at the same time these are preventable. In India, the entire population is prone to IDD due to deficiency of iodine in the soil of the subcontinent and consequently the food derived from it. To combat the risk of IDD, salt is fortified with iodine. However, an estimated 350 million people do not consume adequately iodized salt and, therefore, are at risk for IDD. Of the 325 districts surveyed in India so far, 263 are IDD-endemic. The current household level iodized salt coverage in India is 91 per cent with 71 per cent households consuming adequately iodized salt. The IDD control goal in India was to reduce the prevalence of IDD below 10 per cent in the entire country by 2012. What is required is a “mission approach” with greater coordination amongst all stakeholders of IDD control efforts in India. Mainstreaming of IDD control in policy making, devising State specific action plans to control IDD, strict implementation of Food Safety and Standards (FSS) Act, 2006, addressing inequities in iodized salt coverage (rural-urban, socio-economic), providing iodized salt in Public Distribution System, strengthening monitoring and evaluation of IDD programme and ensuring sustainability of IDD control activities are essential to achieve sustainable elimination of IDD in India. PMID:24135192

  8. A review on the metabolic disorders of iodine deficiency.

    PubMed

    Mansourian, Azad Reza

    2011-04-01

    Iodine is in the crucial parts of two hormones of T4 and T3 produced by the thyroid glands which are essential for all the aspects of human metabolisms. It is demonstrated that iodine deficiency can be considered as sole cause of many thyroid abnormalities including mental disorders. Iodine deficiency of sufficient degree to cause hypothyroidism during fetus life and early infancy will be accompanied with brain abnormality possibly to the stage of mental retardation. The iodine deficiency among subjects in their early stage of childhood is not as severe as those in their fetus or infancy. In adult subjects the sever iodine deficiency can be also associated with mental disorders due to the direct side effects of hypothyroidism occurred by lack of iodine. The clinical manifestation of iodine deficiency show itself with psychological disorders in adult subjects. The status of iodine within blood can be evaluated through measurement of urinary iodine level and the low urinary concentration is an indicative of hypothyroidism. Mental retardation and brain damage due to iodine deficiency can be prevented if iodine supplementation prescribed duly on time. PMID:21902053

  9. Screening for thyroid disease and iodine deficiency.

    PubMed

    Eastman, Creswell J

    2012-02-01

    The high global prevalence of iodine deficiency and autoimmune thyroid disorders and the mental and physical consequences of these disorders creates a huge human and economic burden that can be prevented, in large part, by early detection and appropriate preventative or therapeutic measures. The availability of sophisticated, sensitive and accurate laboratory testing procedures provides an efficient and effective platform for the application of screening for these disorders. Measurement of urine iodine concentration (UIC) in school children or pregnant women is the recommended indicator for screening populations for iodine deficiency. The severity of the iodine deficiency is classified according to the UIC. Measurement of serum thyrotropin (TSH) as an indicator for population iodine deficiency is used only in neonates and is supplementary to UIC screening. Other indicators such as goitre rates, thyroid function and serum thyroglobulin levels are useful adjunctive but not frontline process indicators. The human and economic benefits of screening for congenital hypothyroidism by measurement of heel-prick TSH have been well documented and justify its universal application. Using this measurement for monitoring population iodine intake is recommended by the World Health Organization but further validation is required before it can be universally recommended. Subclinical thyroid dysfunction is readily detected by current highly sensitive serum TSH assays and its prevalence appears to increase with age, varies with iodine intake and ethnicity and may occur in up to 20% of older age people. Subclinical hyperthyroidism is the less common disorder and screening cannot be justified because of its low prevalence and minimal or insignificant clinical effects. The argument for screening for subclinical hypothyroidism in middle-aged and older women is stronger but lacks evidence of benefit from randomised controlled trials or cost benefit analyses of therapeutic intervention, so

  10. Iodine deficiency, other trace elements, and goitrogenic factors in the etiopathogeny of iodine deficiency disorders (IDD).

    PubMed

    Thilly, C H; Vanderpas, J B; Bebe, N; Ntambue, K; Contempre, B; Swennen, B; Moreno-Reyes, R; Bourdoux, P; Delange, F

    1992-01-01

    Severe goiter, cretinism, and the other iodine deficiency disorders (IDD) have their main cause in the lack of availability of iodine from the soil linked to a severe limitation of food exchanges. Apart from the degrees of severity of the iodine deficiency, the frequencies and symptomatologies of cretinism and the other IDD are influenced by other goitrogenic factors and trace elements. Thiocyanate overload originating from consumption of poorly detoxified cassava is such that this goitrogenic factor aggravates a relative or a severe iodine deficiency. Very recently, a severe selenium deficiency has also been associated with IDD in the human population, whereas in animals, it has been proven to play a role in thyroid function either through a thyroidal or extrathyroidal mechanism. The former involves oxidative damages mediated by free radicals, whereas the latter implies an inhibition of the deiodinase responsible for the utilization of T4 into T3. One concludes that: 1. Goiter has a multifactorial origin; 2. IDD are an important public health problem; and 3. IDD are a good model to study the effects of other trace elements whose actions in many human metabolisms have been somewhat underestimated.

  11. Iodine deficiency, other trace elements, and goitrogenic factors in the etiopathogeny of iodine deficiency disorders (IDD).

    PubMed

    Thilly, C H; Vanderpas, J B; Bebe, N; Ntambue, K; Contempre, B; Swennen, B; Moreno-Reyes, R; Bourdoux, P; Delange, F

    1992-01-01

    Severe goiter, cretinism, and the other iodine deficiency disorders (IDD) have their main cause in the lack of availability of iodine from the soil linked to a severe limitation of food exchanges. Apart from the degrees of severity of the iodine deficiency, the frequencies and symptomatologies of cretinism and the other IDD are influenced by other goitrogenic factors and trace elements. Thiocyanate overload originating from consumption of poorly detoxified cassava is such that this goitrogenic factor aggravates a relative or a severe iodine deficiency. Very recently, a severe selenium deficiency has also been associated with IDD in the human population, whereas in animals, it has been proven to play a role in thyroid function either through a thyroidal or extrathyroidal mechanism. The former involves oxidative damages mediated by free radicals, whereas the latter implies an inhibition of the deiodinase responsible for the utilization of T4 into T3. One concludes that: 1. Goiter has a multifactorial origin; 2. IDD are an important public health problem; and 3. IDD are a good model to study the effects of other trace elements whose actions in many human metabolisms have been somewhat underestimated. PMID:1375059

  12. Hypervalent iodine(III)-induced oxidative [4+2] annulation of o-phenylenediamines and electron-deficient alkynes: direct synthesis of quinoxalines from alkyne substrates under metal-free conditions.

    PubMed

    Okumura, Sota; Takeda, Youhei; Kiyokawa, Kensuke; Minakata, Satoshi

    2013-10-18

    Hypervalent iodine(III)-induced oxidative [4+2] annulation of o-phenylenediamines and electron-deficient alkynes under metal-free conditions has been developed. The reaction allows for direct access to quinoxalines bearing two electron-withdrawing groups in an efficient manner.

  13. Iodine Deficiency in Australia: Be Alarmed. Opinions & Perspectives

    ERIC Educational Resources Information Center

    McElduff, Aidan; Beange, Helen

    2004-01-01

    Iodine deficiency, the leading preventable cause of intellectual impairment in the world (World Health Organization, 1999), has reappeared in Australia. Recently, we identified the re-emergence of iodine deficiency in Sydney (Gunton, Hams, Fiegert & McElduff, 1999). This has been confirmed locally (Li, Ma, Boyages & Eastman, 2001) and…

  14. Teratology public affairs committee position paper: iodine deficiency in pregnancy.

    PubMed

    Obican, Sarah G; Jahnke, Gloria D; Soldin, Offie P; Scialli, Anthony R

    2012-09-01

    Iodine deficiency is an important nutritional deficiency, with more than 2 billion people worldwide estimated to be at risk. The developing fetus and young children are particularly at risk. During pregnancy and lactation, iodine requirements increase, whether in iodine-poor or iodine-sufficient countries, making the mother and the developing fetus vulnerable. The American Thyroid Association (ATA) recommends 250 micrograms per day of iodine intake for pregnant and lactating women. The thyroid gland is able to adapt to the changes associated with pregnancy as long as sufficient iodine is present. Dietary intake is the sole source of iodine, which is essential to the synthesis of thyroid hormones. Iodine is found in multiple dietary sources including iodized salt, dairy products, seaweed, and fish. Prenatal vitamins containing iodine are a good source of iodine, but iodine content in multivitamin supplements is highly variable. Congenital hypothyroidism is associated with cretinism. Clinical hypothyroidism has been associated with increased risk of poor perinatal outcome including prematurity, low birth weight, miscarriage, preeclampsia, fetal death, and impaired fetal neurocognitive development. Subclinical hypothyroidism is also associated with poor pregnancy outcomes and potential fetal neurocognitive deficits, but the data are more variable than those for clinical hypothyroidism. We concur with the ATA recommendation that all pregnant and lactating women should ingest (through diet and supplements) 250 micrograms of iodine daily. To achieve this goal, we recommend that all pregnant and lactating women take daily iodine supplementation of 150 micrograms.

  15. Towards the eradication of iodine-deficiency disorders in Brazil through a salt iodination programme.

    PubMed

    Medeiros-Neto, G A

    1988-01-01

    Iodine-deficiency disorders have been a serious public health problem in Brazil because of the failure of a salt iodination programme established in 1953. The reasons for this failure were logistical, e.g., potassium iodide was not supplied to all salt-producers, iodination of salt was largely erratic, and part of the population at risk used only non-refined salt, which was not iodinated. In 1978 a task force was therefore formed to implement measures to eliminate iodine-deficiency disorders from the country. For this purpose, potassium iodate was distributed, free-of-charge, to all salt mills and an iodate dosing spray was supplied without cost to small salt producers. Also, regional laboratories for determining iodine in salt were set up, inspectors made regular visits to the salt mills, and samples of salt from commerce and from the producers were analysed. More than 90% of the samples contained 10-30 mg iodine per kg. In three typical areas of the country with endemic goitre the urinary excretion of iodine increased from an average of less than 40 mug iodine to 125 +/- 38 mug iodine per g creatinine. In conclusion, the salt iodination programme was a complete success and could serve as a model for other countries with a high prevalence of iodine-deficiency disorders.

  16. Current global iodine status and progress over the last decade towards the elimination of iodine deficiency.

    PubMed Central

    Andersson, Maria; Takkouche, Bahi; Egli, Ines; Allen, Henrietta E.; de Benoist, Bruno

    2005-01-01

    OBJECTIVE: To estimate worldwide iodine nutrition and monitor country progress towards sustained elimination of iodine deficiency disorders. METHODS: Cross-sectional data on urinary iodine (UI) and total goitre prevalence (TGP) in school-age children from 1993-2003 compiled in the WHO Global Database on Iodine Deficiency were analysed. The median UI was used to classify countries according to the public health significance of their iodine nutrition status. Estimates of the global and regional populations with insufficient iodine intake were based on the proportion of each country's population with UI below 100 microg/l. TGP was computed for trend analysis over 10 years. FINDINGS: UI data were available for 92.1% of the world's school-age children. Iodine deficiency is still a public health problem in 54 countries. A total of 36.5% (285 million) school-age children were estimated to have an insufficient iodine intake, ranging from 10.1% in the WHO Region of the Americas to 59.9% in the European Region. Extrapolating this prevalence to the general population generated an estimate of nearly two billion individuals with insufficient iodine intake. Iodine intake was more than adequate, or excessive, in 29 countries. Global TGP in the general population was 15.8%. CONCLUSION: Forty-three countries have reached optimal iodine nutrition. Strengthened UI monitoring is required to ensure that salt iodization is having the desired impact, to identify at-risk populations and to ensure sustainable prevention and control of iodine deficiency. Efforts to eliminate iodine deficiency should be maintained and expanded. PMID:16175826

  17. Iodine Deficiency and the Brain: Effects and Mechanisms.

    PubMed

    Redman, Kahla; Ruffman, Ted; Fitzgerald, Penelope; Skeaff, Sheila

    2016-12-01

    Iodine is an essential micronutrient needed in human diets. As iodine is an integral component of thyroid hormone, it mediates the effects of thyroid hormone on brain development. Iodine deficiency is the most prevalent and preventable cause of mental impairment in the world. The exact mechanism through which iodine influences the brain is unclear, but is generally thought to begin with genetic expression. Many brain structures and systems appear to be affected with iodine deficiency, including areas such as the hippocampus, microstructures such as myelin, and neurotransmitters. The clearest evidence comes from the studies examining cognition in the cases of iodine deprivation or interventions involving iodine supplementation. Nevertheless, there are many inconsistencies and gaps in the literature of iodine deficiency, especially over the lifespan. This paper summarizes the literature on this topic, suggests a causal mechanism for iodine's effect on the brain, and indicates areas for the future research (e.g., using magnetic resonance imaging (MRI) and functional MRI to examine how iodine supplementation facilitates cognitive functioning). PMID:25880137

  18. [Effects of the iodine deficiency on intellectual variables among children].

    PubMed

    Muela Martínez, José Antonio; García León, Ana; Torres Barahona, Rosario; Santiago Fernández, Piedad; Sóriguer Escofet, Federico

    2008-05-01

    An association between severe iodine deficiency and poor mental development has been found in many studies. We examined the relationship between moderate or mild iodine deficiency and intellectual capacity in order to determine whether problems common to severe iodine deficiency (including mental retardation) also emerge in a more subtle form. We also wished to know whether the classic methodology (comparing iodine-deficient zones with nondeficient zones) is the most adequate, and propose to combine this grouping by zones with urinary iodine presented by individuals in each zone. We measured IQ, manipulative and verbal capacity, attention, visual motor ability and disruptive behaviour, variables that have barely been studied in this kind of investigations. The sample comprised 760 schoolchildren from the province of Jaén (southern Spain). Our results show that children with low levels of iodine intake and with urinary iodine concentration lower than 100 microg/litre had a lower IQ and displayed more disruptive behaviour than children with high levels of the criteria. The other variables were not associated with iodine deficiency. PMID:18413091

  19. Consuming iodine enriched eggs to solve the iodine deficiency endemic for remote areas in Thailand

    PubMed Central

    2010-01-01

    Background Evidence showed that the occurrence of iodine deficiency endemic areas has been found in every provinces of Thailand. Thus, a new pilot programme for elimination of iodine deficiency endemic areas at the community level was designed in 2008 by integrating the concept of Sufficient Economic life style with the iodine biofortification of nutrients for community consumption. Methods A model of community hen egg farm was selected at an iodine deficiency endemic area in North Eastern part of Thailand. The process for the preparation of high content iodine enriched hen food was demonstrated to the farm owner with technical transfer in order to ensure the sustainability in the long term for the community. The iodine content of the produced iodine enriched hen eggs were determined and the iodine status of volunteers who consumed the iodine enriched hen eggs were monitored by using urine iodine excretion before and after the implement of iodine enrichment in the model farm. Results The content of iodine in eggs from the model farm were 93.57 μg per egg for the weight of 55 - 60 g egg and 97.76 μg for the weight of 60 - 65 g egg. The biological active iodo-organic compounds in eggs were tested by determination of the base-line urine iodine of the volunteer villagers before and after consuming a hard boiled iodine enriched egg per volunteer at breakfast for five days continuous period in 59 volunteers of Ban Kew village, and 65 volunteers of Ban Nong Nok Kean village. The median base-line urine iodine level of the volunteers in these two villages before consuming eggs were 7.00 and 7.04 μg/dL respectively. After consuming iodine enriched eggs, the median urine iodine were raised to the optimal level at 20.76 μg/dL for Ban Kew and 13.95 μg/dL for Ban Nong Nok Kean. Conclusions The strategic programme for iodine enrichment in the food chain with biological iodo-organic compound from animal origins can be an alternative method to fortify iodine in the diet for

  20. Iodine

    MedlinePlus

    ... the amount depends on the iodine in the soil where they grew and in any fertilizer that ... babies. People living in regions with iodine-deficient soils who eat mostly local foods. These soils produce ...

  1. [Iodine excess induced thyroid dysfunction].

    PubMed

    Egloff, Michael; Philippe, Jacques

    2016-04-20

    The principle sources of iodine overload, amiodarone and radiologic contrast media, are frequently used in modern medicine. The thyroid gland exerts a protective effect against iodine excess by suppressing iodine internalization into the thyrocyte and iodine organification, the Wolff-Chaikoff effect. Insufficiency of this effect or lack of escape from it leads to hypo- or hyperthyroidism respectively. Amiodarone induced thyrotoxicosis is a complex condition marked by two different pathophysiological mechanisms with different treatments. Thyroid metabolism changes after exposure to radiologic contrast media are frequent, but they rarely need to be treated. High risk individuals need to be identifed in order to delay the exam or to monitor thyroid function or apply prophylactic measures in selected cases. PMID:27276725

  2. [Iodine excess induced thyroid dysfunction].

    PubMed

    Egloff, Michael; Philippe, Jacques

    2016-04-20

    The principle sources of iodine overload, amiodarone and radiologic contrast media, are frequently used in modern medicine. The thyroid gland exerts a protective effect against iodine excess by suppressing iodine internalization into the thyrocyte and iodine organification, the Wolff-Chaikoff effect. Insufficiency of this effect or lack of escape from it leads to hypo- or hyperthyroidism respectively. Amiodarone induced thyrotoxicosis is a complex condition marked by two different pathophysiological mechanisms with different treatments. Thyroid metabolism changes after exposure to radiologic contrast media are frequent, but they rarely need to be treated. High risk individuals need to be identifed in order to delay the exam or to monitor thyroid function or apply prophylactic measures in selected cases.

  3. The story of iodine deficiency: An international challenge in nutrition

    SciTech Connect

    Hetzel, B.S.

    1989-01-01

    Iodine deficiency is a risk factor for the growth and development of up to 800 million people living in iodine deficient environments throughout the world. The effects on growth and development, called the iodine deficiency disorders (IDD), comprise goiter, stillbirths and miscarriages, neonatal and juvenile thyroid deficiency, dwarfism, mental defects, deaf mutism, and spastic weakness and paralysis, as well as lesser degrees of loss of physical and mental function. All these effects are due to inadequate thyroid hormone production because iodine is an essential constituent of the thyroid hormone. In the West, IDD has been largely eliminated by the addition of iodine to the diet through iodized salt or through changes in food distribution and technology. IDD still persists in certain areas of Europe where these dietary changes have not occurred. In the Third World, IDD is a major problem in many countries with large populations, such as China, India, Indonesia, Nigeria, and Zaire. In these and other Third World countries, IDD is a significant barrier to social and economic progress which can be removed by correction of the deficiency. This book shows that elimination of iodine deficiency is feasible within the next decade, only requiring a modest financial and technical effort from the West. Part 1 reviews IDD in man and animals. Part 2 discusses the control of iodine deficiency disorders through iodine supplementation, and considers action at the national and international level. Part 3 presents a global review of the status of IDD control. There is a brief conclusion on the way forward to successful control programs.

  4. Neurocognitive outcomes of children secondary to mild iodine deficiency in pregnant women.

    PubMed

    Caron, Philippe

    2015-07-01

    Iodine deficiency is the most important preventable cause of brain damage worldwide. During pregnancy, severe iodine deficiency causes endemic cretinism, whereas mild-to-moderate iodine deficiency impairs neurocognitive function of the offspring. Numerous reports demonstrate the impact of iodine supplementation on prevention of cretinism, and recent studies evaluate the effects of iodine prophylaxis on neurocognitive development in children of women with mild-to-moderate iodine deficiency. Iodine prophylaxis is generally well tolerated without side effects for the pregnant women and the offspring. In France, the iodine status was recently considered as satisfactory in children and adult population, but regional studies conducted during the last two decades have shown that healthy women are mild-to-moderately iodine deficient during pregnancy. According to recent World Heath Organization guidelines, systematic iodine prophylaxis is recommended in women planning a pregnancy, during gestation and lactation in order to prevent maternal, neonatal and infantile consequences of mild-to-moderate iodine deficiency. PMID:25934357

  5. Neurocognitive outcomes of children secondary to mild iodine deficiency in pregnant women.

    PubMed

    Caron, Philippe

    2015-07-01

    Iodine deficiency is the most important preventable cause of brain damage worldwide. During pregnancy, severe iodine deficiency causes endemic cretinism, whereas mild-to-moderate iodine deficiency impairs neurocognitive function of the offspring. Numerous reports demonstrate the impact of iodine supplementation on prevention of cretinism, and recent studies evaluate the effects of iodine prophylaxis on neurocognitive development in children of women with mild-to-moderate iodine deficiency. Iodine prophylaxis is generally well tolerated without side effects for the pregnant women and the offspring. In France, the iodine status was recently considered as satisfactory in children and adult population, but regional studies conducted during the last two decades have shown that healthy women are mild-to-moderately iodine deficient during pregnancy. According to recent World Heath Organization guidelines, systematic iodine prophylaxis is recommended in women planning a pregnancy, during gestation and lactation in order to prevent maternal, neonatal and infantile consequences of mild-to-moderate iodine deficiency.

  6. Iodine deficiency, thyroid function and hearing deficit: a review.

    PubMed

    Melse-Boonstra, Alida; Mackenzie, Ian

    2013-12-01

    Iodine deficiency affects an estimated 241 million school-aged children in the world. Little is known about iodine deficiency in relation to auditory function, except for the fact that deaf-mutism is one of the features of cretinism. In the present review, we documented the scientific knowledge on the role of iodine and hypothyroidism in the auditory system. We found that ear development and hearing function depend on thyroid hormones. Multiple pathways are involved in this, including both inner ear morphology as well as neurological processes. Conductive as well as sensorineural hearing loss is found in studies with animals that were rendered hypothyroidic. In humans, auditory impairment is reported frequently in relation to hypothyroidism, ranging from mild disturbances to severe handicap. Auditory impairment has been related more explicitly to congenital hypothyroidism than to acquired hypothyroidism. The critical period for thyroid function-related hearing maturation is the first and second trimesters of pregnancy. Although only a limited number of studies have directly investigated the relationship between iodine deficiency and auditory function, most studies point toward an association. However, evidence from good randomised controlled trials is lacking. Inclusion of auditory outcomes in iodine supplementation studies is therefore to be recommended, especially for trials in pregnancy. Hearing deficit is an invisible abnormality, but has major consequences for educational and social skills if not detected. In view of this, auditory impairment should be mapped in iodine-deficient areas in order to realistically estimate the magnitude of the problem.

  7. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.

    PubMed

    Contempre, B; Dumont, J E; Ngo, B; Thilly, C H; Diplock, A T; Vanderpas, J

    1991-07-01

    Selenium and seleno dependent glutathione peroxidase (GPX) deficiency has been described in endemias of myxedematous cretinism. In northern Zaire, a selenium supplementation trial has been conducted. Beside correcting the GPX activity, two months of selenium supplementation was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects. These results further support a role of selenium in thyroid hormone metabolism. In an iodine deficient area, this selenium deficiency could lead to opposite clinical consequences: protect the general population and the fetus against iodine deficiency and brain damage; and in turn, favour the degenerative process of the thyroid gland leading to myxoedematous cretinism. PMID:2045471

  8. Successful efforts toward elimination iodine deficiency disorders in India.

    PubMed

    Kapil, Umesh

    2010-10-01

    Iodine deficiency (ID) is the world's single most important preventable cause of brain damage and mental retardation. Iodine deficiency disorders (IDDs) is a public health problem in 130 countries, affecting 13% of the world population. The simplest solution to prevent the IDD is to consume iodized common salt every day. In India, significant progress has been achieved toward elimination of IDD, in the last 30 years. Satisfactory levels of urinary iodine excretion and iodine content of salt have been documented by the research surveys conducted by research scientists. The results indicate that we are progressing toward elimination of IDD. IDD is due to a nutritional deficiency, which is prima-rily that of iodine, in soil and water. IDD is known to re-appear if the IDD Control Program is not sustained. To ensure that the population continues to have intake of adequate amount of iodine, there is a need of i) periodic surveys to assess the magnitude of the IDD with respect to impact of iodized salt (IS) intervention; ii) strengthening the health and nutrition education activities to create demand for IS and iii) development of a monitoring information system (MIS) for ensuring that the adequately IS is available to the beneficiaries. PMID:21278862

  9. The epidemiology of iodine-deficiency diseases in China.

    PubMed

    Ma, T; Guo, J; Wang, F

    1993-02-01

    Iodine-deficiency diseases (IDDs) are wide-spread in China, distributed mainly in the inland and mountainous regions. About one-third of the total Chinese population lives in IDD-endemic areas. The severity of IDD is related to the severity of iodine deficiency. All the selenium-deficient areas of China are also IDD-endemic areas; however, IDD can be very severe in areas where selenium status is thought to be adequate. The distribution of myxedematous cretinism in China is not related to selenium deficiency. In the Tarim Basin, the selenium status of the population is normal and myxedematous cretinism is prevalent. In the northeastern regions of China, selenium deficiency is common and neurological cretinism is very rare.

  10. Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns.

    PubMed

    Pearce, Elizabeth N; Lazarus, John H; Moreno-Reyes, Rodrigo; Zimmermann, Michael B

    2016-09-01

    Severe iodine deficiency during development results in maternal and fetal hypothyroidism and associated serious adverse health effects, including cretinism and growth retardation. Universal salt iodization is the first-line strategy for the elimination of severe iodine deficiency. Iodine supplementation is recommended for vulnerable groups in severely iodine-deficient regions where salt iodization is infeasible or insufficient. A recent clinical trial has informed best practices for iodine supplementation of severely iodine-deficient lactating mothers. Because of successful programs of universal salt iodization in formerly severely iodine-deficient regions around the world, public health concern has shifted toward mild to moderate iodine deficiency, which remains prevalent in many regions, especially among pregnant women. Observational studies have shown associations between both mild maternal iodine deficiency and mild maternal thyroid hypofunction and decreased child cognition. Iodine supplementation has been shown to improve indexes of maternal thyroid function, even in marginally iodine-deficient areas. However, no data are yet available from randomized controlled trials in regions of mild to moderate iodine insufficiency on the relation between maternal iodine supplementation and neurobehavioral development in the offspring; thus, the long-term benefits and safety of such supplementation are uncertain. Although it is clear that excessive iodine intake can cause alterations in thyroid function in susceptible individuals, safe upper limits for iodine intake in pregnancy have not been well defined. Well-designed, prospective, randomized controlled trials that examine the effects of iodine supplementation on maternal thyroid function and infant neurobehavioral development in mildly to moderately iodine-deficient pregnant women are urgently needed. In addition, clinical data on the effects of iodine excess in pregnant and lactating women are needed to inform

  11. Urinary iodine concentrations indicate iodine deficiency in pregnant Thai women but iodine sufficiency in their school-aged children.

    PubMed

    Gowachirapant, Sueppong; Winichagoon, Pattanee; Wyss, Laura; Tong, Bennan; Baumgartner, Jeannine; Melse-Boonstra, Alida; Zimmermann, Michael B

    2009-06-01

    The median urinary iodine concentration (UI) in school-aged children is recommended for assessment of iodine nutrition in populations. If the median UI is adequate in school-aged children, it is usually assumed iodine intakes are also adequate in the remaining population, including pregnant women. But iodine requirements sharply increase during pregnancy. In this study, our aim was to measure UI in pairs of pregnant women and their school-aged children from the same family, who were sharing meals, to directly assess whether a household food basket that supplies adequate iodine to school-aged children also meets the needs of pregnant women. UI was measured in spot urine samples from pairs (n = 302) of healthy pregnant mothers and their school-aged children in metropolitan Bangkok, Thailand. A dietary questionnaire was completed. The UI [median (range)] in the pregnant women {108 (11-558) microg/L [0.85 (0.086-4.41) micromol/L]} were lower than those of their school-aged children {200 (25-835) microg/L [1.58 (0.20-6.52) micromol/L]} (P < 0.001), indicating optimal iodine status in the children but mild-to-moderate iodine deficiency in their pregnant mothers. The estimated iodine intakes in the 2 groups were in the range of 130-170 microg/d. There was a modest positive correlation between UI in the pairs (r = 0.253; P < 0.01). A higher frequency of seafood meals was a significant predictor of UI in both groups, but household use of iodized salt was not. These data suggest the median UI in school-aged children should not be used as a surrogate for monitoring iodine status in pregnancy in central Thailand; pregnant women should be directly monitored.

  12. Addition of chlorine during water purification reduces iodine content of drinking water and contributes to iodine deficiency.

    PubMed

    Samson, L; Czegeny, I; Mezosi, E; Erdei, A; Bodor, M; Cseke, B; Burman, K D; Nagy, E V

    2012-01-01

    Drinking water is the major natural source of iodine in many European countries. In the present study, we examined possible sites of iodine loss during the usual water purification process.Water samples from 6 sites during the technological process were taken and analyzed for iodine content. Under laboratory circumstances, prepared iodine in water solution has been used as a model to test the effect of the presence of chlorine. Samples from the purification sites revealed that in the presence of chlorine there is a progressive loss of iodine from the water. In the chlorine concentrations employed in the purification process, 24-h chlorine exposure eliminated more than 50% of iodine when the initial iodine concentration was 250 μg/l or less. Iodine was completely eliminated if the starting concentration was 16 μg/l.We conclude that chlorine used during water purification may be a major contributor to iodine deficiency in European communities.

  13. Developmental iodine deficiency and hypothyroidism impair neural development, upregulate caveolin-1, and downregulate synaptotagmin-1 in the rat cerebellum.

    PubMed

    Wang, Yi; Zhong, Jiapeng; Wei, Wei; Gong, Jian; Dong, Jing; Yu, Fei; Wang, Yuan; Chen, Jie

    2011-12-01

    Adequate thyroid hormone is critical for cerebellar development. Developmental hypothyroidism induced by iodine deficiency during gestation and postnatal period results in permanent impairments of cerebellar development with an unclear mechanism. In the present study, we implicate cerebellar caveolin-1 and synaptotagmin-1, the two important molecules involved in neuronal development, in developmental iodine deficiency, and in developmental hypothyroidism. Two developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 or 15 ppm)-added drinking water from gestational day 6 till postnatal day (PN) 28. Nissl staining and the levels of caveolin-1 and synaptotagmin-1 in cerebella were assessed on PN28 and PN42. The results show that the numbers of Purkinje cells were reduced in the iodine-deficient and PTU-treated rats. The upregulation of caveolin-1 and the downregulation of synaptotagmin-1 were observed in both iodine-deficient and PTU-treated rats. These findings may implicate decreases in the number of Purkinje cells and the alterations in the levels of caveolin-1 and synaptotagmin-1 in the impairments of cerebellar development induced by developmental iodine deficiency and hypothyroidism.

  14. Monitoring and effects of iodine deficiency in pregnancy: still an unsolved problem?

    PubMed

    Pearce, E N

    2013-05-01

    Iodine is required for the production of thyroid hormone. Thyroid hormone affects many metabolic processes in the body, including maturation of the central nervous system. In early pregnancy, the fetus is dependent on maternal thyroid hormone for normal brain development. If iodine deficiency leads to inadequate production of thyroid hormone during pregnancy, irreversible brain damage can result in the fetus. Therefore, achieving adequate iodine nutrition during pregnancy is an important public health objective. Although there have been tremendous gains over the last several decades in our understanding of the effects of iodine deficiency in pregnancy and how to combat them, a number of questions remain about how best to monitor the iodine status of pregnant populations, the effects of mild to moderate iodine deficiency on maternal and child outcomes, the safe upper limit of daily iodine intake in pregnant women and the risks and benefits of iodine supplementation for mildly iodine-deficient pregnant women.

  15. Elimination of Mental Defect Due to Iodine Deficiency by the Year 2000.

    ERIC Educational Resources Information Center

    Hetzel, Basil S.

    1993-01-01

    This paper reviews the effects of iodine deficiency across the lifespan, with special reference to mental defect; discusses the magnitude of the problem; describes available iodine technology to control iodine deficiency disorders (IDD); and notes the status of national IDD control programs, to assess the likelihood of eliminating IDD by the year…

  16. Hypothyroidism and iodine deficiency in an infant requiring total parenteral nutrition.

    PubMed

    Clarridge, Katherine Elizabeth; Conway, Erin E; Bucuvalas, John

    2014-09-01

    While iodine deficiency remains a relatively rare cause of thyroid dysfunction in the United States, little is known about iodine status and deficiency in children requiring parenteral nutrition (PN). This population may be at an elevated risk of thyroid dysregulation and neurodevelopmental sequelae due to low concentrations in typical PN formulations. Furthermore, with the widespread practice of switching from iodine-based antiseptics to chlorhexadine, previous inadvertent sources of iodine are being eliminated as well.

  17. Symposium on 'Geographical and geological influences on nutrition': Iodine deficiency in industrialised countries.

    PubMed

    Zimmermann, Michael B

    2010-02-01

    Iodine deficiency is not only a problem in developing regions; it also affects many industrialised countries. Globally, two billion individuals have an insufficient iodine intake, and approximately 50% of continental Europe remains mildly iodine deficient. Iodine intakes in other industrialised countries, including the USA and Australia, have fallen in recent years. Iodine deficiency has reappeared in Australia, as a result of declining iodine residues in milk products because of decreased iodophor use by the dairy industry. In the USA, although the general population is iodine sufficient, it is uncertain whether iodine intakes are adequate in pregnancy, which has led to calls for iodine supplementation. The few available data suggest that pregnant women in the Republic of Ireland and the UK are now mildly iodine deficient, possibly as a result of reduced use of iodophors by the dairy industry, as observed in Australia. Representative data on iodine status in children and pregnant women in the UK are urgently needed to inform health policy. In most industrialised countries the best strategy to control iodine deficiency is carefully-monitored salt iodisation. However, because approximately 90% of salt consumption in industrialised countries is from purchased processed foods, the iodisation of household salt only will not supply adequate iodine. Thus, in order to successfully control iodine deficiency in industrialised countries it is critical that the food industry use iodised salt. The current push to reduce salt consumption to prevent chronic diseases and the policy of salt iodisation to eliminate iodine deficiency do not conflict; iodisation methods can fortify salt to provide recommended iodine intakes even if per capita salt intakes are reduced to <5 g/d. PMID:19968908

  18. Iodine deficiency in pregnancy, infancy and childhood and its consequences for brain development.

    PubMed

    Melse-Boonstra, Alida; Jaiswal, Nidhi

    2010-02-01

    Iodine deficiency during foetal development and early childhood is associated with cognitive impairment. Randomised clinical studies in school-aged children encountered in the literature indicate that cognitive performance can be improved by iodine supplementation, but most studies suffer from methodological constraints. Tests to assess cognitive performance in the domains that are potentially affected by iodine deficiency need to be refined. Maternal iodine supplementation in areas of mild-to-moderate iodine deficiency may improve cognitive performance of the offspring, but randomised controlled studies with long-term outcomes are lacking. Studies in infants or young children have not been conducted. The best indicators for iodine deficiency in children are thyroid-stimulating hormone (TSH) in newborns and thyroglobulin (Tg) in older children. Urinary iodine may also be useful but only at the population level. Adequate salt iodisation will cover the requirements of infants and children as well as pregnant women. However, close monitoring remains essential.

  19. Iodine and selenium deficiency associated with cretinism in northern Zaire.

    PubMed

    Vanderpas, J B; Contempré, B; Duale, N L; Goossens, W; Bebe, N; Thorpe, R; Ntambue, K; Dumont, J; Thilly, C H; Diplock, A T

    1990-12-01

    Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa.

  20. Iodine and selenium deficiency associated with cretinism in northern Zaire.

    PubMed

    Vanderpas, J B; Contempré, B; Duale, N L; Goossens, W; Bebe, N; Thorpe, R; Ntambue, K; Dumont, J; Thilly, C H; Diplock, A T

    1990-12-01

    Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa. PMID:2239787

  1. [Distribution iodine deficiency diseases in coastal areas depending on geochemical conditions].

    PubMed

    Kiku, P F; Andryukov, B G

    2014-01-01

    In the Primorsky Krai there was performed a population ecological and hygienic analysis of the relationship between the content of chemical elements in the soil and thyroid morbidity in the population of the region. The assessment of the prevalence of iodine deficiency and iodine deficiency diseases was carried out on the basis of the impact of the priority environmental toxic (strontium, nickel, cadmium, lead, arsenic, tin) and essential (nickel, iron, germanium, molybdenum, zinc, selenium) trace elements on the level of iodine deficiency diseases. The level of thyroid pathology in the territory of Primorye was established to be the highest one in areas characterized by the severe iodine deficiency (Northwest geochemical zones), where the structure of thyroid diseases is presented mainly by diffuse nontoxic goiter. Thyroid diseases associated with iodine deficiency in the population of different age groups are the result of multiple and combined imbalance of trace elements, which causes a relative (secondary) iodine deficiency. Thyroid disease in Primorye are environmentally caused diseases of technogenic origin, they are a consequence of the relative iodine deficiency, when on the background of normal iodine supply an imbalance of zinc, iron, cobalt, manganese with excess of such toxic trace elements as lead, strontium, nickel and chromium takes place. Thyroid pathology associated with iodine deficiency, along with other environmentally dependent diseases can be considered as a marker of ecological environment trouble. PMID:25831939

  2. [Distribution iodine deficiency diseases in coastal areas depending on geochemical conditions].

    PubMed

    Kiku, P F; Andryukov, B G

    2014-01-01

    In the Primorsky Krai there was performed a population ecological and hygienic analysis of the relationship between the content of chemical elements in the soil and thyroid morbidity in the population of the region. The assessment of the prevalence of iodine deficiency and iodine deficiency diseases was carried out on the basis of the impact of the priority environmental toxic (strontium, nickel, cadmium, lead, arsenic, tin) and essential (nickel, iron, germanium, molybdenum, zinc, selenium) trace elements on the level of iodine deficiency diseases. The level of thyroid pathology in the territory of Primorye was established to be the highest one in areas characterized by the severe iodine deficiency (Northwest geochemical zones), where the structure of thyroid diseases is presented mainly by diffuse nontoxic goiter. Thyroid diseases associated with iodine deficiency in the population of different age groups are the result of multiple and combined imbalance of trace elements, which causes a relative (secondary) iodine deficiency. Thyroid disease in Primorye are environmentally caused diseases of technogenic origin, they are a consequence of the relative iodine deficiency, when on the background of normal iodine supply an imbalance of zinc, iron, cobalt, manganese with excess of such toxic trace elements as lead, strontium, nickel and chromium takes place. Thyroid pathology associated with iodine deficiency, along with other environmentally dependent diseases can be considered as a marker of ecological environment trouble.

  3. Neurological signs in congenital iodine-deficiency disorder (endemic cretinism).

    PubMed

    DeLong, G R; Stanbury, J B; Fierro-Benitez, R

    1985-06-01

    Neurological examinations were made of 67 children and adults with congenital iodine-deficiency disorder (endemic cretinism) in four rural villages in highland Ecuador. There was a distinct and readily identifiable pattern of neurological deficits. These included, to varying degrees: deaf-mutism or lesser degrees of bilateral hearing-loss or dysarthria; spasticity, particularly involving the proximal lower extremities; mental deficiency of a characteristic type; and rigidity and bradykinesia. Not all of these elements were found in all cases. Less common features were strabismus, kyphoscoliosis and frontal-lobe signs. There were exceptional cases with hypotonia. In contrast, cerebellar function was largely spared, as were functions of emotion and attention, vegetative and autonomic functions, social interaction, and probably memory, except in the most severely involved. PMID:4018426

  4. The impact of iodine supplementation and bread fortification on urinary iodine concentrations in a mildly iodine deficient population of pregnant women in South Australia.

    PubMed

    Clifton, Vicki L; Hodyl, Nicolette A; Fogarty, Paul A; Torpy, David J; Roberts, Rachel; Nettelbeck, Ted; Ma, Gary; Hetzel, Basil

    2013-01-01

    Mild iodine deficiency during pregnancy can have significant effects on fetal development and future cognitive function. The purpose of this study was to characterise the iodine status of South Australian women during pregnancy and relate it to the use of iodine-containing multivitamins. The impact of fortification of bread with iodized salt was also assessed. Women (n = 196) were recruited prospectively at the beginning of pregnancy and urine collected at 12, 18, 30, 36 weeks gestation and 6 months postpartum. The use of a multivitamin supplement was recorded at each visit. Spot urinary iodine concentrations (UIC) were assessed. Median UICs were within the mildly deficient range in women not taking supplements (<90 μg/L). Among the women taking iodine-containing multivitamins UICs were within WHO recommendations (150-249 μg/L) for sufficiency and showed an increasing trend through gestation. The fortification of bread with iodized salt increased the median UIC from 68 μg/L to 84 μg/L (p = .011) which was still in the deficient range. Pregnant women in this region of Australia were unlikely to reach recommended iodine levels without an iodine supplement, even after the mandatory iodine supplementation of bread was instituted in October 2009.

  5. Iodine deficiency: Physiological, clinical and epidemiological features, and pre-analytical considerations.

    PubMed

    Doggui, Radhouene; El Atia, Jalila

    2015-02-01

    Low dietary intake is associated with severe pathologies (especially goiter and cretinism) that affect life quality. Iodine deficiency disorders are a major public health problem worldwide. In fact, 246 million school-aged children have insufficient iodine intake (data from 2012). Extrapoling this value to general population leads to the estimation that 1.9 billion people have insufficient iodine intake. So, it is crucial to interpret correctly data from iodine status survey. The World Health Organization recommends urinary iodine as the main indicator for the assessment of iodine status in epidemiological surveys. To improve the result, some considerations can be taken into account by the biologist, epidemiologist or public health physician for the realization of epidemiological surveys. After a reminder about the physiological and physiopathological feature of iodine, a description of some useful parameters was made to improve the exploration of iodine status in epidemiological surveys.

  6. [Effectiveness of the program "School Milk" for the prevention of iodine deficiency].

    PubMed

    Danilenko, A L; Kamilov, F Kh; Mamtsev, A N; Kozlov, V N; Ponomarev, E E

    2015-01-01

    Republic of Bashkortostan refers to iodine-deficient regions of Russia. The incidence of endemic multinodular goiter in 2012 in the Republic amounted to 33.2 per 100 thousand of the population. The purpose of the study is to evaluate the effectiveness of group iodine prophylaxis of schoolchildren through the use of iodized milk. The study included 181 children of primary school (pre-pubertal) age (8-10 years), it has been carried out in accordance with the recommendations of the WHO and the International Council for Control of iodine deficiency disorders using a unified system of identification of iodine deficiency states. Level of physical development was assessed according to anthropometric measurements, which were conducted by centile distribution tables according to age and sex, and the individual assessment of physical development was determined by the level of feature by its position in a number of centile. Assessment of iodine deficiency was carried out by determining levels of iodine excretion in a single urine sample. Iodine concentration in urine was determined by ceric ion-arsenious acid method. Frequency of iodine deficiency varying degrees before the iodine prophylaxis among urban children was 57.0%, among rural-92.3%. Urban junior schoolchildren showed severe iodine deficiency in 12.7% and moderate one in 16.4% of the cases, while in the countryside their prevalence was higher--27.4 and 35.2%, respectively. It was revealed that the number of children whose body growth values are within the average values is 36% in urban children, and 48.4% in rural areas. It should be noted that the low and very low body height predominate in rural students, it makes up 16.1% (while in the town it makes-up 2.3%). Iodine prophylaxis contributed to a significant reduction of iodine deficiency in children. In the town the median urinary iodine exceeded 100 mg/L and amounted to 159.4 mg/L. After iodine prophylaxis 82.5% of urban children and 72.1% of rural showed normal

  7. Iodine deficiency in pregnant women living in the South-East of the UK: the influence of diet and nutritional supplements on iodine status

    PubMed Central

    Bath, Sarah C.; Walter, Alan; Taylor, Andrew; Wright, John; Rayman, Margaret P.

    2015-01-01

    Iodine is a key component of the thyroid hormones which are crucial for brain development. Pregnant women are vulnerable to iodine deficiency because their requirement for iodine is higher than that of non-pregnant adults. Data on the iodine status of UK pregnant women are sparse and there are no such data in the South East. One hundred pregnant women were recruited to a cross-sectional study at the Royal Surrey County Hospital, Guildford, at their first-trimester visit for an ultrasound scan. Participants provided a spot-urine sample (for the measurement of urinary iodine and creatinine concentrations) and 24-hour excretion of iodine was estimated from the urinary iodine-to-creatinine ratio. Women completed a general questionnaire and a food-frequency questionnaire. The median urinary iodine concentration (85·3 μg/l) indicated that the group was iodine deficient by WHO criteria. The median values of the iodine-to-creatinine ratio (122·9 μg/g) and of the estimated 24-hr iodine excretion (151·2 μg/day) were also suggestive of iodine deficiency. Urinary iodine concentration was significantly higher in women taking an iodine-containing prenatal supplement (n=42) than in those not taking such a supplement (P<0·001). In adjusted analyses, milk intake, maternal age and iodine-containing prenatal supplement use were positively associated with estimated 24-hour urinary iodine excretion. Our finding of iodine deficiency in these women gives cause for concern. We suggest that women of childbearing age and pregnant women should be given advice on how to improve their iodine status through dietary means. A national survey of iodine status in UK pregnant women is required. PMID:24398008

  8. Developmental iodine deficiency delays the maturation of newborn granule neurons associated with downregulation of p35 in postnatal rat hippocampus.

    PubMed

    Yu, Fei; Wang, Yi; Xu, Hongde; Dong, Jing; Wei, Wei; Wang, Yuan; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

    2014-08-01

    We evaluated the role of p35 in the maturation of hippocampal granule neurons in offspring caused by developmental iodine deficiency. Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil-adulterated water (5 ppm) to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day 28. The protein levels of p35, cyclin-dependent kinase 5, β-catenin, and N-cadherin were assessed on postnatal day 14, 21, and 28. Dendritic morphogenesis of newborn granule neurons in dentate gyrus was examined. Developmental hypothyroidism induced by iodine deficiency and PTU treatment delayed the maturation of hippocampal granule neurons in the offspring and decreased the percentage of Dcx-positive neurons that expressed β-catenin on postnatal day 21 and 28. In addition, downregulation of p35 was observed in dentate gyrus of hypothyroid groups. Developmental hypothyroidism induced by iodine deficiency and PTU treatment could delay the maturation of newborn granule neurons in dentate gyrus, and this deficit may be attributed to the downregulation of p35.

  9. Eliminating iodine deficiency disorders--the role of the International Council in the global partnership.

    PubMed Central

    Hetzel, Basil S.

    2002-01-01

    Iodine deficiency is the most common preventable cause of brain damage. WHO estimates that some 2.2 billion people are at risk from iodine deficiency in 130 countries. A programme of universal salt iodization was established in 1994 with the aim of eliminating the problem by 2000. This paper reports progress in this field, with particular reference to the primarily scientific role of the International Council for Control of Iodine Deficiency Disorders, a nongovernmental organization founded in 1986. It is now a multidisciplinary network of 600 professionals in 100 countries. PMID:12077619

  10. Iodine deficiency in pregnancy: the effect on neurodevelopment in the child.

    PubMed

    Skeaff, Sheila A

    2011-02-01

    Iodine is an integral part of the thyroid hormones, thyroxine (T(4)) and tri-iodothyronine (T(3)), necessary for normal growth and development. An adequate supply of cerebral T(3), generated in the fetal brain from maternal free T(4) (fT(4)), is needed by the fetus for thyroid hormone dependent neurodevelopment, which begins in the second half of the first trimester of pregnancy. Around the beginning of the second trimester the fetal thyroid also begins to produce hormones but the reserves of the fetal gland are low, thus maternal thyroid hormones contribute to total fetal thyroid hormone concentrations until birth. In order for pregnant women to produce enough thyroid hormones to meet both her own and her baby's requirements, a 50% increase in iodine intake is recommended. A lack of iodine in the diet may result in the mother becoming iodine deficient, and subsequently the fetus. In iodine deficiency, hypothyroxinemia (i.e., low maternal fT(4)) results in damage to the developing brain, which is further aggravated by hypothyroidism in the fetus. The most serious consequence of iodine deficiency is cretinism, characterised by profound mental retardation. There is unequivocal evidence that severe iodine deficiency in pregnancy impairs brain development in the child. However, only two intervention trials have assessed neurodevelopment in children of moderately iodine deficient mothers finding improved neurodevelopment in children of mothers supplemented earlier rather than later in pregnancy; both studies were not randomised and were uncontrolled. Thus, there is a need for well-designed trials to determine the effect of iodine supplementation in moderate to mildly iodine deficient pregnant women on neurodevelopment in the child. PMID:22254096

  11. Iodine deficiency in pregnant women living in the South East of the UK: the influence of diet and nutritional supplements on iodine status.

    PubMed

    Bath, Sarah C; Walter, Alan; Taylor, Andrew; Wright, John; Rayman, Margaret P

    2014-05-01

    Iodine is a key component of the thyroid hormones which are crucial for brain development. Adequate intake of iodine in pregnancy is important as in utero deficiency may have lifelong consequences for the offspring. Data on the iodine status of UK pregnant women are sparse, and there are no such data for pregnant women in the South East of the UK. A total of 100 pregnant women were recruited to a cross-sectional study carried out at the Royal Surrey County Hospital, Guildford, at their first-trimester visit for an ultrasound scan. The participants provided a spot-urine sample (for the measurement of urinary iodine concentration (UIC) and creatinine concentration) and 24 h iodine excretion was estimated from the urinary iodine:creatinine ratio. Women completed a general questionnaire and a FFQ. The median UIC (85·3 μg/l) indicated that the group was iodine deficient by World Health Organisation criteria. The median values of the iodine:creatinine ratio (122·9 μg/g) and of the estimated 24 h iodine excretion (151·2 μg/d) were also suggestive of iodine deficiency. UIC was significantly higher in women taking an iodine-containing prenatal supplement (n 42) than in those not taking such a supplement (P< 0·001). In the adjusted analyses, milk intake, maternal age and iodine-containing prenatal supplement use were positively associated with the estimated 24 h urinary iodine excretion. Our finding of iodine deficiency in these women gives cause for concern. We suggest that women of childbearing age and pregnant women should be given advice on how to improve their iodine status through dietary means. A national survey of iodine status in UK pregnant women is required.

  12. Opposite variations in maternal and neonatal thyroid function induced by iodine supplementation during pregnancy.

    PubMed

    Nøhr, S B; Laurberg, P

    2000-02-01

    Whereas the consequences of extremes in iodine intake are well described, much less is known about the effect of more moderate variations in maternal iodine intake on fetal thyroid function. The present study performed in Denmark with mild to moderate iodine deficiency dealt with the effect of maternal iodine supplementation on thyroid function in the mother at term and in the fetus/neonate. Serum was collected consecutively from pregnant women at term (n = 144) and from cord blood (n = 139). Forty-nine women had a regular intake of vitamin and mineral tablets with iodine (150 microg/day) during pregnancy, and 95 took no artificial iodine supplementation. Iodine supplementation (+I) induced opposite variations in thyroid function in the mother and the fetus. In +I mothers, TSH was 7.6% lower than in mothers with no supplementation (P < 0.05). In cord blood, on the contrary, TSH was 27.3% higher in the +I group (P < 0.05). The variations were caused by opposite shifts in TSH frequency distribution in mothers and neonates. The association between iodine supplementation and high serum TSH in the neonates was further substantiated by an inverse correlation between thyroglobulin and TSH in cord blood (P < 0.001), whereas no specific pattern was observed in the mothers. High serum thyroglobulin was a marker of low iodine intake in both mothers and neonates. The results suggest that the fetal thyroid, at least in areas of mild iodine deficiency, is more sensitive to the inhibitory effect of iodine than hitherto anticipated.

  13. Iodization of village water supply in the control of endemic iodine deficiency in rural Sarawak, Malaysia.

    PubMed

    Foo, L C; Zainab, T; Goh, S Y; Letchuman, G R; Nafikudin, M; Doraisingam, P; Khalid, B

    1996-09-01

    A simple water iodizing system, which incorporates the Venturi principle in combination with the controlled release mechanism of a silicone-sodium iodide elastomer, for the iodization of rural piped-water supply in the control of endemic iodine deficiency has been developed and its effectiveness evaluated in three Iban longhouse villages in the iodine-deficient district of Lubok Antu, Sarawak. Urines were collected for iodine assays from women aged 15-40 years before and at 6 and 12 months after the connection of the iodinating device; goiter assessment was performed on the women at the start and end of the 1-year study. Water samples were collected for iodine assays at 2-weekly intervals. In all three villages, significant and sustained increases in median urinary iodine excretions, reaching levels recommended for an iodine-sufficient population, were observed; goitre prevalences were reduced in all the villages (by 22.6% to 35.8%). The iodine levels in the water ranged from 34 micrograms/l to 212 micrograms/L. In the control village, median urinary iodine excretions remained essentially unchanged but a small increase in goiter prevalence was observed. The iodized water was well received by the villagers and no adverse effects of water iodization were observed. The system functioned unattended throughout the one year period. The cost of providing supplemental iodine via the iodizing device is approximately 60 cents (U.S.) per family per year which is affordable by either the Government or the villagers. It is concluded that the iodizing system offers a new cost-effective strategy for the control of endemic iodine deficiency in Sarawak and may have applications in other areas with similar water sources. PMID:8886337

  14. Iodine-Induced Hypothyroidism in Full-term Infants With Congenital Heart Disease: More Common Than Currently Appreciated?

    PubMed Central

    Leung, A. M.; Braverman, L. E.; Brown, R. S.; Levine, B.

    2014-01-01

    Context: Iodine is a micronutrient essential for thyroid hormone synthesis. Thyroid hormone is critical for normal neurocognitive development in young infants, and even transient hypothyroidism can cause adverse neurodevelopmental outcomes. Both iodine deficiency and excess can cause hypothyroidism. Although iodine-induced hypothyroidism is well recognized in premature infants, full-term neonates have received less attention. Infants with congenital heart disease (CHD) are commonly exposed to excess iodine from administration of iodinated contrast agents during cardiac catheterization as well as topical application of iodine-containing antiseptics and dressings; hence, this is a vulnerable population. Objective: We report three cases of iodine-induced hypothyroidism in full-term neonates with CHD after cardiac angiography and topical application of iodine-containing antiseptics and dressings in the operative setting. Results: Three neonates with CHD and normal thyroid function at birth developed hypothyroidism after exposure to excess iodine. Two of these infants had transient hypothyroidism, and one had severe hypothyroidism requiring ongoing thyroid replacement therapy. All infants were asymptomatic, with hypothyroidism detected incidentally in the inpatient setting due to repeat newborn screening mandated by the long duration of hospitalization in these infants. Conclusions: Iodine-induced hypothyroidism may be under-recognized in infants with CHD exposed to excess iodine. Systematic monitoring of thyroid function should be considered to avoid potential long-term adverse neurodevelopmental effects of even transient thyroid dysfunction in this susceptible population. PMID:25004248

  15. Laser Induced Fluorescence of the Iodine Ion

    NASA Astrophysics Data System (ADS)

    Hargus, William

    2014-10-01

    Iodine (I2) has been considered as a potential electrostatic spacecraft thruster propellant for approximately 2 decades, but has only recently been demonstrated. Energy conversion efficiency appears to be on par with xenon without thruster modification. Intriguingly, performance appears to exceed xenon at high acceleration potentials. As part of a continuing program for the development of non-intrusive plasma diagnostics for advanced plasma spacecraft propulsion, we have identified the I II 5d5D4 o state as metastable, and therefore containing a reservoir of excited state ions suitable for laser probing. The 5d5D4 o - 6p5P3 transition at 695.878 nm is convenient for diode laser excitation with the 5s5S2 o - 6p5P3 transition at 516.12 nm as an ideal candidate for non-resonant fluorescence collection. We have constructed a Penning type iodine microwave discharge lamp optimized for I II production for table-top measurements. This work demonstrates I II laser-induced fluorescence in a representative iodine discharge and will validate our previous theoretical work based on the limited available historical I II spectral data.

  16. Statistical design considerations applicable to clinical trials of iodine supplementation in pregnant women who may be mildly iodine deficient.

    PubMed

    Troendle, James F

    2016-09-01

    No large, randomized, placebo-controlled trial of iodine supplementation in pregnant women in a region of mild or moderate iodine deficiency has been completed in which a primary outcome measure was an assessment of the neurobehavioral development of the offspring at age ≥2 y. In this article, I discuss considerations for the design of such a trial in a region of mild iodine deficiency, with a focus on statistical methods and approaches. Exposure and design issues include the ethics of using a placebo, the potential for overexposure to iodine, and the possibility of community randomization. The main scientific goal of the trial is important in determining the follow-up period. If the goal is to determine whether iodine supplementation during pregnancy improves neurobehavioral development in the offspring, then follow-up should continue until a reasonably reliable assessment can be conducted, which might be at age ≥2 y. Once the timing of assessment is decided, the impact of potential loss to follow-up should be considered so that appropriate statistical methods can be incorporated into the design. The minimum sample size can be calculated by using a sample size formula that incorporates noncompliance and assumes that a certain proportion of study participants do not have any outcome observed. To have sufficient power to detect a reasonably modest difference in neurobehavioral development scores using an assessment tool with an SD of 15, a large number of participants (>500/group) is required. The minimum adequate number of participants may be even larger (>1300/group) depending on the magnitude of the difference in outcome between the supplementation and placebo groups, the estimated proportion of the iodine-supplementation group that fails to take the supplement, and the estimated proportion of pregnancies that do not produce outcome measurements. PMID:27534639

  17. Statistical design considerations applicable to clinical trials of iodine supplementation in pregnant women who may be mildly iodine deficient.

    PubMed

    Troendle, James F

    2016-09-01

    No large, randomized, placebo-controlled trial of iodine supplementation in pregnant women in a region of mild or moderate iodine deficiency has been completed in which a primary outcome measure was an assessment of the neurobehavioral development of the offspring at age ≥2 y. In this article, I discuss considerations for the design of such a trial in a region of mild iodine deficiency, with a focus on statistical methods and approaches. Exposure and design issues include the ethics of using a placebo, the potential for overexposure to iodine, and the possibility of community randomization. The main scientific goal of the trial is important in determining the follow-up period. If the goal is to determine whether iodine supplementation during pregnancy improves neurobehavioral development in the offspring, then follow-up should continue until a reasonably reliable assessment can be conducted, which might be at age ≥2 y. Once the timing of assessment is decided, the impact of potential loss to follow-up should be considered so that appropriate statistical methods can be incorporated into the design. The minimum sample size can be calculated by using a sample size formula that incorporates noncompliance and assumes that a certain proportion of study participants do not have any outcome observed. To have sufficient power to detect a reasonably modest difference in neurobehavioral development scores using an assessment tool with an SD of 15, a large number of participants (>500/group) is required. The minimum adequate number of participants may be even larger (>1300/group) depending on the magnitude of the difference in outcome between the supplementation and placebo groups, the estimated proportion of the iodine-supplementation group that fails to take the supplement, and the estimated proportion of pregnancies that do not produce outcome measurements.

  18. Influence of iodine deficiency and iodine prophylaxis on thyroid cancer histotypes and incidence in endemic goiter area.

    PubMed

    Huszno, B; Szybiński, Z; Przybylik-Mazurek, E; Stachura, J; Trofimiuk, M; Buziak-Bereza, M; Gołkowski, F; Pantoflinski, J

    2003-01-01

    The aim of the study was to evaluate the correlation between thyroid cancer histotype and incidence rate (IR) and iodine nutrition level in two endemic goiter areas: the districts of Krakow and Nowy Sacz. The suspension of iodine prophylaxis in Poland in 1980 resulted in increased goiter prevalence in schoolchildren and adults and elevated TSH levels in newborns in the early 1990s. Since 1992 a rise in thyroid cancer IR was observed. Thyroid cancer IR in the Krakow population was 2.22 in 1986; 3.62 in 1995 and 6.02 in 2001; in Nowy Sacz: 1.52; 2.59 and 3.88 respectively. In 1986 papillary/follicular cancer ratio in both areas was about 1.0--the value typical of iodine deficient areas. After restoring the obligatory iodine prophylaxis in 1997, a significant decrease in elevated TSH concentration in newborns and urinary iodine concentration increase in schoolchildren were observed. A relative rise in the incidence of papillary thyroid cancer and decrease in follicular cancer, resulting in rise in papillary/follicular thyroid cancer ratio up to 5.9 in 2001 was also observed. Since 1999 no further thyroid cancer IR increase was noted. In conclusion, a significant increase in differentiated thyroid cancer IR was observed in association with the iodine prophylaxis suspension. Changes in thyroid cancer histotypes in 1986-2001 and a significant decrease in incremental rate of differentiated thyroid cancer probably reflect the influence of effective iodine prophylaxis. The significant difference between IR of thyroid cancer incidence in the districts of Krakow and Nowy Sacz may be related to differences in the exposure to radiation after the Chernobyl accident. PMID:12762644

  19. Early gestation screening of pregnant women for iodine deficiency disorders and iron deficiency in urban centre in Vadodara, Gujarat, India.

    PubMed

    Joshi, K; Nair, S; Khade, C; Rajan, M G R

    2014-02-01

    Pregnancy is a special condition where many metabolic changes may occur because of increased requirement of essential micronutrients such as iron and iodine. Foetal thyroid starts producing its own thyroid hormones after 12 weeks of gestation. Therefore, the first trimester is very crucial for meeting thyroid hormone requirements of the mother and foetus. Iodine deficiency and iron deficiency may affect mental and physical growth of the foetus. Hence, it is very important to establish a programme on the screening of pregnant women for thyroid dysfunction tests along with established iron status assessment. Thus, the study was aimed to screen the pregnant women for iodine deficiency disorders and iron deficiency during early gestation, situational analysis on thyroid insufficiency and iron deficiency in pregnant women (gestational age <15 weeks) in urban Vadodara, Gujarat. n = 256 healthy pregnant women with uncomplicated singleton pregnancy were selected. The thyroid hormone was estimated by RIA, UIE using simple microplate technique and haemoglobin (Hb) concentration by acid hematin method. Median thyrotropin (TSH), free thyroxine (FT4), total thyroxine (TT4) and UIE concentrations were 1.88 μIU/ml, 0.83 ng/dl, 10.24 μg/dl and 297.14 mcg/l, respectively. There was a significant correlation between TSH, FT4 and month of gestation. Mean Hb concentration was 9.27 ± 1.09 g/dl. The prevalence of iodine insufficiency (based on UI) was 16.79% and iron deficiency was 91%. Screening programme for iodine deficiency during early gestation should be implemented along with the existing programme of haemoglobin estimation at first prenatal visit. This would help prevent damage to the developing brain and growth of the foetus and also to trace at-risk pregnant women. PMID:24847692

  20. Post-production losses in iodine concentration of salt hamper the control of iodine deficiency disorders: a case study in northern Ethiopia.

    PubMed

    Shawel, Dawit; Hagos, Seifu; Lachat, Carl K; Kimanya, Martin E; Kolsteren, Patrick

    2010-06-01

    Iodine is essential for good function of the thyroid, and its deficiency is of public-health importance in Ethiopia. Iodization of salt is an effective and sustainable strategy to prevent and control iodine deficiency in large populations. The effectiveness of salt-iodization programmes depends on the conservation of iodine concentration in salt at various stages of the supply-chain. The overall objective of the study was to assess the loss of iodine in salt from production to consumption and to estimate the proportion of adults, especially pregnant women, at risk of dietary iodine insufficiency. A cross-sectional study was conducted during February-April 2007 in northern Ethiopia. Iodine concentrations of salt samples from producers (n=41), retailers (n=7), and consumers (n=32) were determined using iodiometric titration. A risk assessment was conducted for dietary iodine insufficiency among adults, including pregnant women, using a semi-probabilistic approach. The concentration of iodine in the sampled salts decreased by 57% from the production site to the consumers. The assessment of exposure showed that adults in 63% (n=20) of the households, including 90% (n=29) with pregnant women, were at risk of insufficient iodine intake. A monitoring and evaluation system needs to be established to ensure adequate supply of iodine along the distribution chain. Special attention is needed for the retailers and consumers. At these levels, dissemination of information regarding proper storage and handling of iodized salt is necessary to address the reported loss of iodine from salt.

  1. Iodine-induced thyroid blockade: role of selenium and iodine in the thyroid and pituitary glands.

    PubMed

    Basalaeva, Nadezdha L

    2013-08-01

    The purpose of this study was to determine the content of iodine and selenium in the thyroid and pituitary glands of rats under iodine-induced blockade of the thyroid gland. Electron probe microanalysis, wavelength-dispersive spectrometry, and point analysis were used in this investigation. We also determined the expression of sodium iodide symporter and caspase 32 in the thyroid and pituitary glands and the expression of thyroid-stimulating hormone in the pituitary. The samples for iodine analysis must be thoroughly dehydrated, and for this purpose, we developed a method that produced samples of constant mass with minimal loss of substrate (human thyroid gland was used for the investigation). Normal levels of iodine and selenium were found in the thyroid, pituitary, ovaries, testes hypothalamus, and pancreas of healthy rats. The levels of iodine and selenium in I- or Se-positive points and the percentage of positive points in most of these organs were similar to those of controls (basal level), except for the level of iodine in the thyroid gland and testes. Blockade of the thyroid gland changed the iodine level in iodine-positive points of the thyroid and the pituitary glands. On the sixth day of blockage, the iodine level in iodine-positive points of the thyroid gradually decreased to the basal level followed by an abrupt increase on the seventh day, implying a rebound effect. The opposite was found in the pituitary, in which the level of iodine in iodine-positive points increased during the first 6 days and then abruptly decreased on the seventh day. Expression of the thyroid-stimulating hormone in the pituitary decreased during the first 5 days but sharply increased on the sixth day, with a minimum level of iodine in the thyroid and maximum in the pituitary, before normalization of the iodine level in both glands preceding the rebound effect. The expression of sodium iodide symporter increased during the first 4 days of blockage and then decreased in both

  2. Strain differences among rats in response to Remington iodine-deficient diets

    SciTech Connect

    Okamura, K.; Taurog, A.; Krulich, L.

    1981-08-01

    Male rats of five different strains (Simonsen albino, Wistar, Long-Evans, Holtzman Sprague-Dawley, and Charles River Sprague-Dawley) were tested for their response to the U.S. Biochemical Corp. Remington low iodine diet containing 15-18 microgram I/kg. Measurements made after the diet had been fed for 28-30 days indicated that Simonsen albino and Wistar strains consistently showed the greatest response, based on degree of thyroid enlargement, depletion of thyroidal iodine, reduction in serum T4, and elevation of serum TSH. Long-Evans and Holtzman Sprague-Dawley rats responded relatively poorly to the low iodine diet. One experiment included female rats, and the limited data suggested that within a given strain there was no significant sex difference. With more prolonged feeding (84 days), the difference between a rapidly responding strain (Simonsen albino) and a more slowly responding strain (Holtzman Sprague-Dawley) was not so marked. Our results indicate that given sufficient time and a diet sufficiently low in iodine, even a more slowly responding strain will ultimately develop signs of extreme iodine deficiency. However, it is inconvenient and expensive to maintain rats on a Remington low iodine diet for 3 months, and studies on the effect of severe iodine deficiency are much more rapidly performed using a rapidly responding strain such as the Simonsen albino. Our observation that rats of different strains differ markedly in their responses to an iodine-deficient diet suggests that hereditary factors play an important role in this response.

  3. Iron induced nickel deficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is increasingly apparent that economic loss due to nickel (Ni) deficiency likely occurs in horticultural and agronomic crops. While most soils contain sufficient Ni to meet crop requirements, situations of Ni deficiency can arise due to antagonistic interactions with other metals. This study asse...

  4. Iodine Deficiency and Hypothyroidism From Voluntary Diet Restrictions in the US: Case Reports.

    PubMed

    Booms, Stephanie; Hill, Elizabeth; Kulhanek, Leah; Vredeveld, Jennifer; Gregg, Brigid

    2016-06-01

    Iodine deficiency is rare in the United States today, and this is largely due to the effectiveness of iodization in the general food supply. Recent trends among specific populations of children in the United States include adopting food restrictions, such casein-free and gluten-free diets. Although the effect of these types of diets on overall nutrition status and certain micronutrients has been studied in children with autism spectrum disorder, the effect of these limitations on iodine levels in children has not been assessed. We present here 2 cases of iodine deficiency resulting from severe food restriction and associated primary hypothyroidism. In 1 case a classic presentation with a goiter was seen. These children were able to discontinue thyroid hormone treatment once iodine levels were normalized. There were no adverse events or unanticipated outcomes. The occurrence of these cases of iodine deficiency in the United States points to the need for thyroid function testing in children with severe food restrictions, especially those who have limited exposure to dairy, baked goods, and table salt.

  5. Iodine plus n-3 fatty acid supplementation augments rescue of postnatal neuronal abnormalities in iodine-deficient rat cerebellum.

    PubMed

    Pal, Amit; Mohan, Vishwa; Modi, Dinesh R; Sinha, Rohit A; Rastogi, Leena; Kumar, Praveen; Godbole, Madan M

    2013-08-01

    High prevalence of hypothyroxinaemia in iodine-deficient (ID) mothers has serious implications for mental health of the progeny. Independent supplementation of iodine and n-3 fatty acids (FA) markedly improves growth and cognitive performance of school children. Discerning effects of n-3 FA and iodine on the developing cerebellum have not been ascertained. The present study investigates effects of these two micronutrients separately as well as together in an ID rat model. We studied the effects of these micronutrients on progeny of ID dams by instituting the following supplementation diets: (1) low-iodine diet (LID), (2) LID+potassium iodide (KI), (3) LID+n-3 FA and (4) LID+KI+n-3 FA. Pups were investigated for morphological and biochemical parameters at the peak of cerebellar histogenesis on postnatal day (P) 16 and for neurobehavioural as well as motor coordination parameters at P40. Results indicate that n-3 FA alone, without improvement in circulating thyroid hormone (TH), significantly improves functional, morphological and biochemical indices of the developing cerebellum. Further, results show that co-supplementation with iodine and n-3 FA rescues not only the loss of neurotrophic support, but also salvages motor coordination, memory and learning. This additive effect results in significantly improving neurotrophic support and seems to be mediated by parallel significant increase in TH receptor (TR)α and normalisation of TRβ, retinoic orphan receptor α and p75 neurotrophin receptor, as well as noteworthy prevention of apoptotic cell death and strengthening of anti-oxidative defence. The overall results indicate important mitigating role that n-3 FA may play in enhancing TH nuclear receptor-mediated signalling in the developing cerebellum. PMID:23312094

  6. Iodine

    MedlinePlus

    ... 6 weeks increases the healing rate. Also, applying povidone-iodine in addition to compression seems help heal ... Catheter-related infection. Some evidence suggests that applying povidone-iodine reduces the risk of blood stream infections ...

  7. Iodine

    USGS Publications Warehouse

    Krukowski, S.T.

    2006-01-01

    In descending order, Chile, Japan and the United States have the largest iodine reserves. Chile produces iodine from iodate minerals while Japan and the United States produce it from sodium iodide solutions found in underground iodide solutions. Iodine is also produced from subterranean brines in Azerbaijan, Russia, Turkmenista, Indonesia and Uzbekistan. In 2005, iodine prices increased sharply to US$19 to US$23 then leveled off at US$23 to US$25.

  8. Selenium status in pregnant women of a rural population (Zaire) in relationship to iodine deficiency.

    PubMed

    Ngo, D B; Dikassa, L; Okitolonda, W; Kashala, T D; Gervy, C; Dumont, J; Vanovervelt, N; Contempré, B; Diplock, A T; Peach, S; Vanderpas, J

    1997-06-01

    Endemic myxoedematous cretinism has been associated with combined selenium and iodine deficiency in several areas of Zaire. To determine selenium and iodine status across the country, serum selenium and thyroid function parameters including urinary iodide were determined at prenatal clinics in 30 health centres of rural villages distributed over the whole country. Only in Bas-Zaire was the mean serum selenium level similar to that in non-deficient areas (80-120 ng/ml); in the regions of Bandunda and Kasai levels were marginally decreased (55-80 ng/ml), and in Kivu, Haut-Zaire, Equateur and Shaba they were marginally or moderately decreased (< 55 ng/ml). The frequency of abnormally low urinary iodide (< 5 micrograms/dl) varied from 20% in the region of Bas-Zaire to 50% in Kasai (P < 0.001), and to still higher percentages in the 5 other regions of Zaire (Bandundu, 57%; Kivu, 63%; Equateur, 72%; Shaba, 76%; Haut-Zaire, 84%). With the exception of Bas-Zaire, biochemical maternal hypothyroidism (serum TSH > 5mU/l) was present in every region, with a frequency ranging from 3% in Kivu to 12% in Equateur. Iodine deficiency affects most of the Zairean population and requires public health measures on a larger scale than previously estimated. Combined iodine and selenium deficiency affects Equateur, Haut-Zaire and Kivu, where endemic myxoedematous cretinism occurs, but also Shaba, where it was not previously described. Besides combined iodine and selenium deficiency which is permissive, another factor (thiocyanate?) must be taken into account to explain the peculiarly elevated prevalence of endemic myxoedematous cretinism in Central Africa. PMID:9236825

  9. Iodine supplementation during pregnancy and lactation. Position statement of the working group on disorders related to iodine deficiency and thyroid dysfunction of the Spanish Society of Endocrinology and Nutrition.

    PubMed

    Donnay, Sergio; Arena, Jose; Lucas, Anna; Velasco, Inés; Ares, Susana

    2014-01-01

    Severe and mild iodine deficiency during pregnancy and lactation affects thyroid function of the mother and neonate as well as the infant's neuropsychological development. Studies performed in Spain confirm that most women are iodine deficient during pregnancy and lactation. Pregnant and breast feeding women and women planning to become pregnant should take iodine supplements.

  10. Effect of thiocyanate levels in milk on thyroid function in iodine deficient subjects.

    PubMed

    Dahlberg, P A; Bergmark, A; Eltom, M; Björck, L; Claesson, O

    1985-05-01

    To utilize the antibacterial effect of the lactoperoxidase system to prevent bacterial spoilage of raw milk it is necessary to increase the thiocyanate concentration of the milk. Thiocyanate has, however, a potent antithyroid effect which is enhanced by iodine deficiency. In this study the thyroid function has been studied, before and after 4 weeks daily administration of 250 ml of such treated milk, in 55 goitrous subjects living in an endemic goiter region of western Sudan. The iodine content was 0.1 mg/l and the thiocyanate content was either 3.6 mg/l (n 19) or 19 mg/l (n 36) in the milk. At the start of the experiment all subjects were iodine deficient with a urinary excretion of 40-50 micrograms/g creatinine. After 4 weeks daily intake of 4.75 mg of thiocyanate by way of milk the serum thiocyanate level increased by approximately 1.7 mg/l. Both at the beginning and at the end of the experimental period the serum levels of thyroxine, triiodothyronine and TSH were in the normal range for all subjects. After 4 weeks the TSH levels had decreased significantly, (from 2.6 +/- 0.2 to 2.1 +/- 0.2 mU/l, p less than 0.001) probably as an effect of the supplementary intake of iodine. The thyroid hormone levels remained unchanged during the experimental period. In conclusion, the intake of milk with an iodine concentration of 0.1 mg/l and a thiocyanate concentration of 19 mg/l does not have a negative effect on the thyroid function in iodine deficient subjects.

  11. SUFFICIENT IODINE INTAKE IN SCHOOLCHILDREN FROM THE ZAGREB AREA: ASSESSMENT WITH DRIED BLOD SPOT THYROGLOBULIN AS A NEW FUNCTIONAL BIOMARKER FOR IODINE DEFICIENCY.

    PubMed

    Jukić, Tomislav; Zimmermann, Michael Bruce; Granić, Roko; Prpić, Marin; Krilić, Drazena; Juresa, Vesna; Katalenić, Marijan; Kusić, Zvonko

    2015-12-01

    Current methods for assessment of iodine intake in a population comprise measurements of urinary iodine concentration (UIC), thyroid volume by ultrasound (US-Tvol), and newborn TSH. Serum or dried blood spot thyroglobulin (DBS-Tg) is a new promising functional iodine status biomarker in children. In 1996, a new act on universal salt iodination was introduced in Croatia with 25 mg of potassium iodideper kg of salt. In 2002, Croatia finally reached iodine sufficiency. However, in 2009, median UIC in 101 schoolchildren from Zagreb, the capital of Croatia, was 288 µg/L, posing to be excessive. The aim of the study was to assess iodine intake in schoolchildren from the Zagreb area and to evaluate the value of DBS-Tg in schoolchildren as a new functional biomarker of iodine deficiency (and iodine excess). The study was part of a large international study in 6- to 12-year-old children supported by UNICEF, the Swiss Federal Institute of Technology (ETH Zurich) and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD). According to international study results, the median cut-off Tg < 13 µg/L and/or < 3% Tg values > 40 µg/L indicate iodine sufficiency. The study included 159 schoolchildren (median age 9.1 ± 1.4 years) from Zagreb and a nearby small town of Jastrebarsko with measurements of UIC, US-Tvol, DBS-Tg, T4, TSH and iodine content in salt from households of schoolchildren (KI/kg of salt). Overall median UIC was 205 µg/L (range 1-505 µg/L). Thyroid volumes in schoolchildren measured by US were within the normal range according to reference values. Median DBS-Tg in schoolchildren was 12.1 µg/L with 3% of Tg values > 40 µg/L. High Tg values were in the UIC range < 50 µg/L and > 300 µg/L (U-shaped curve of Tg plotted against UIC). All children were euthyroid with geometric mean TSH 0.7 ± 0.3 mU/L and arithmetic mean T4 62 ± 12.5 nmol/L. The mean KI content per kg of salt was 24.9 ± 3.1 mg/kg (range 19-36 mg/kg). Study results

  12. SUFFICIENT IODINE INTAKE IN SCHOOLCHILDREN FROM THE ZAGREB AREA: ASSESSMENT WITH DRIED BLOD SPOT THYROGLOBULIN AS A NEW FUNCTIONAL BIOMARKER FOR IODINE DEFICIENCY.

    PubMed

    Jukić, Tomislav; Zimmermann, Michael Bruce; Granić, Roko; Prpić, Marin; Krilić, Drazena; Juresa, Vesna; Katalenić, Marijan; Kusić, Zvonko

    2015-12-01

    Current methods for assessment of iodine intake in a population comprise measurements of urinary iodine concentration (UIC), thyroid volume by ultrasound (US-Tvol), and newborn TSH. Serum or dried blood spot thyroglobulin (DBS-Tg) is a new promising functional iodine status biomarker in children. In 1996, a new act on universal salt iodination was introduced in Croatia with 25 mg of potassium iodideper kg of salt. In 2002, Croatia finally reached iodine sufficiency. However, in 2009, median UIC in 101 schoolchildren from Zagreb, the capital of Croatia, was 288 µg/L, posing to be excessive. The aim of the study was to assess iodine intake in schoolchildren from the Zagreb area and to evaluate the value of DBS-Tg in schoolchildren as a new functional biomarker of iodine deficiency (and iodine excess). The study was part of a large international study in 6- to 12-year-old children supported by UNICEF, the Swiss Federal Institute of Technology (ETH Zurich) and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD). According to international study results, the median cut-off Tg < 13 µg/L and/or < 3% Tg values > 40 µg/L indicate iodine sufficiency. The study included 159 schoolchildren (median age 9.1 ± 1.4 years) from Zagreb and a nearby small town of Jastrebarsko with measurements of UIC, US-Tvol, DBS-Tg, T4, TSH and iodine content in salt from households of schoolchildren (KI/kg of salt). Overall median UIC was 205 µg/L (range 1-505 µg/L). Thyroid volumes in schoolchildren measured by US were within the normal range according to reference values. Median DBS-Tg in schoolchildren was 12.1 µg/L with 3% of Tg values > 40 µg/L. High Tg values were in the UIC range < 50 µg/L and > 300 µg/L (U-shaped curve of Tg plotted against UIC). All children were euthyroid with geometric mean TSH 0.7 ± 0.3 mU/L and arithmetic mean T4 62 ± 12.5 nmol/L. The mean KI content per kg of salt was 24.9 ± 3.1 mg/kg (range 19-36 mg/kg). Study results

  13. Investigation of iodine deficient state and iodine supplementation in patients with severe motor and intellectual disabilities on long-term total enteral nutrition.

    PubMed

    Takeuchi, Takako; Kamasaki, Hotaka; Yoto, Yuko; Honjo, Takashi; Tsugawa, Satoshi; Hotsubo, Tomoyuki; Tsutsumi, Hiroyuki

    2012-01-01

    Iodine concentrations of enteral nutrition (EN) formulae available in Japan are very low and long-term total EN (TEN) might result in hypothyroidism due to iodine deficiency (HID). Our aim of this study was to determine the degree of iodine deficiency (ID) and need for iodine supplementation (IS) in patients with severe motor and intellectual disabilities (SMID) on long-term TEN. Thyroid function including urinary iodine concentration (UIC) was monitored, and powdered kelp was provided as a source of iodine supplement. Thirty-five SMID on TEN participated in our study. UIC less than 100 μg /L, representing ID, were detected in 97 % of them. Their TSH ranged from 0.5 to 90 μIU/mL. IS using powdered kelp raised their UIC to the normal range. Thyroid function also recovered in the five hypothyroidism cases, which were diagnosed as HID, was also detected. In Japan, there must be many cases with ID associated with long term TEN. We also discuss the regulation of thyroid function in the iodine deficient state. PMID:22673532

  14. The perinatal thyroid in iodine deficient regions: risks of radioiodines--hazards of stable iodine overload. A study in the newborn rat.

    PubMed

    Hindié, E; Walker, F; Petiet, A; Bourahla, K; Galle, P; Colas-Linhart, N

    2001-05-01

    Administration of large quantities of stable iodine is an effective means of reducing the radiation burden on the thyroid in the event of a nuclear power-plant accident. Such administration may involve countries with low baseline dietary iodine intake. It is questioned whether stable iodine overload is safe, and in particular, what are its effects in newborn infants? Iodine-deficient newborn rats were submitted to a single acute administration of stable iodine (100 microg) on the second day of life. The effects on thyroid structure were studied, after 24 hr and after 7 days, using light microscopy. Compared to controls, the thyroids of animals submitted to stable iodine overload showed, 7 days after treatment, signs of acute toxicity including marked desquamation of epithelial cells and rupture of a large number of thyroid follicles. Our findings in iodine deficient newborn rats suggest that stable iodine overload may have side effects during perinatal life. This prophylactic measure should, therefore, be accompanied by follow-up of thyroid function. Thyroid hormones are critical for brain development, during the first period of life. PMID:11441946

  15. Overweight increases risk of first trimester hypothyroxinaemia in iodine-deficient pregnant women.

    PubMed

    Gowachirapant, Sueppong; Melse-Boonstra, Alida; Winichagoon, Pattanee; Zimmermann, Michael B

    2014-01-01

    Hypothyroxinaemia early in pregnancy may impair fetal brain development. Increased body weight has been associated with low thyroxine concentrations in non-pregnant women. In pregnant women, morbid maternal obesity is a risk factor for thyroid dysfunction. But whether lesser degrees of overweight that are much more common could be a risk factor for hypothyroxinaemia in pregnancy is unclear. The objective of this study was to investigate if overweight increases risk for thyroid dysfunction, and specifically hypothyroxinaemia, in iodine-deficient pregnant women. We performed a cross-sectional study at first hospital visit among healthy Thai pregnant women. We measured weight and height, urinary iodine concentration (UIC), serum thyroid hormones and thyroglobulin. Pre-pregnancy weight and relevant dietary factors were determined by questionnaire, and body mass index (BMI) was used to classify weight status. Among 514 women (mean gestational age, 11 weeks) with a median UIC of 111 μg dL(-1) , indicating mild iodine deficiency, 12% had low free thyroxine (fT4) concentrations: 3% had overt hypothyroidism; 7% had subclinical hypothyroidism; and 8% had isolated hypothyroxinaemia. Based on pre-pregnancy BMI, 26% of women were overweight or obese. In a multiple regression model, BMI was a negative predictor of fT4 (β = -0.20, P < 0.001). Compared to normal weight women, the prevalence ratio (95% CI) of a low fT4 in overweight women was 3.64 (2.08-6.37) (P < 0.01). Iodine-deficient pregnant Thai women who are overweight have a 3.6-fold higher risk of hypothyroxinaemia in the first trimester compared to normal weight women. Targeted screening should consider overweight a potential risk factor for thyroid dysfunction in pregnant women in iodine-deficient areas.

  16. Effects of iodine concentration on iodine-induced stress corrosion cracking of zircaloy-4 tube

    NASA Astrophysics Data System (ADS)

    Woo, Seog Ryu; Young, Hwan Kang; Lee, Jai-Young

    1988-05-01

    Iodine-induced stress corrosion cracking (I-SCC) experiments on Zircaloy-4 tube were undertaken in the iodine concentration range of 0-4 mg/cm 2, the temperature range of 330-400 ° C and a nominal hoop stress of 475 MPa, using the internal pressurization method. The time-to-failure, failure strain and strain rate were measured as a function of the iodine concentration. An apparent activation energy for I-SCC was calculated from the temperature dependence of I-SCC. A fractographic interpretation was also made through scanning electron microscopic examination. The results suggest that the iodine concentration has an influence on the crack propagation step to increase the propagation rate of I-SCC, promoting the I-SCC susceptibility. It is found that the critical iodine concentration means the phenomenological value to show the iodine concentration dependence of I-SCC susceptibility, not the critical value to determine the occurrence of I-SCC. The I-SCC behavior of Zircaloy is discussed from the viewpoint of the crack initiation and propagation process.

  17. [Mental development disorders and attention-deficit syndrome caused by iodine deficiency: a clinical and epidemiological study].

    PubMed

    Zhukov, A O

    2007-01-01

    A clinical and epidemiological study including 2,397 children of school age living in the areas with different levels of or without iodine deficiency has been carried out. An increased frequency of cases with IQ not more than 80-85 scores was observed in iodine deficient areas. Iodine deficiency was a cause of clinically diagnosed borderline development delay only in 7% of children. Attention deficit syndrome (without hyperactivity) and anxiety-depressive disorders as well as asthenic symptoms were observed most frequently. Basing on the literature data and own observations, the author suggests a hypothesis on the pathogenetic basis of these disorders. PMID:18379482

  18. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy.

    PubMed

    Pharoah, Pod; Buttfield, I H; Hetzel, B S

    2012-06-01

    Endemic cretinism is characterised by multiple neurological defects including deaf-mutism, diplegia, squint, and mental deficiency. The condition is widely prevalent in the Highlands of New Guinea in association with severe iodine deficiency. Previous studies have shown that iodised oil provides a very satisfactory correction of severe iodine deficiency in New Guinea. A controlled trial on the use of intramuscular iodised oil in the prevention of endemic cretinism was carried out in the Western Highlands of New Guinea and involved a population of approximately 8000. Subsequent follow-up over four years revealed 26 endemic cretins out of a total of 534 children born to mothers who had not received iodised oil; the mothers of 5 of these cretins were pregnant at the start of the trial. In comparison, 7 cases of endemic cretinism occurred among 498 children born to mothers who had been treated with iodised oil; in 6 of these 7 cases, the mother was pregnant when the trial commenced. It is concluded that intramuscular iodised oil is effective in the prevention of endemic cretinism and that, for it to be effective, it should be given prior to conception. This suggests that severe iodine deficiency in the mother produces neurological damage during fetal development. PMID:22586135

  19. Status of iodine deficiency amongst school children in twenty four districts in southern India.

    PubMed

    Kapil, Umesh; Singh, Preeti; Dwivedi, Sada Nand

    2005-01-01

    The central legislation banning sale of non-iodized salt for edible purposes in the entire country was withdrawn by the Government in the year 2000. The present study was conducted in the year 2001 immediately after lifting the central ban to establish the baseline urinary iodine excretion levels in twenty four districts of Southern India. In each district all the senior secondary schools were enlisted and one school was selected by random sampling. About 120 children in the age group of 11 to 18 years were selected using the random number tables. The urinary iodine excretion levels were analysed using the wet digestion method. It was found that districts Rangareddy, Kolar, Yanam and Perambalour had median UIE levels less than 100 microg/l, indicating iodine deficiency. The findings of the present study highlights the success of Universal salt iodisation programme. The Government of India should reinitiate the process of central ban on sale of non iodised salt in the country to prevent the iodine deficiency disorders.

  20. Tanzania national survey on iodine deficiency: impact after twelve years of salt iodation

    PubMed Central

    Assey, Vincent D; Peterson, Stefan; Kimboka, Sabas; Ngemera, Daniel; Mgoba, Celestin; Ruhiye, Deusdedit M; Ndossi, Godwin D; Greiner, Ted; Tylleskär, Thorkild

    2009-01-01

    Background In many low-income countries, children are at high risk of iodine deficiency disorders, including brain damage. In the early 1990s, Tanzania, a country that previously suffered from moderate to severe iodine deficiency, adopted universal salt iodation (USI) as an intervention strategy, but its impact remained unknown. Methods We report on the first national survey in mainland Tanzania, conducted in 2004 to assess the extent to which iodated salt was used and its apparent impact on the total goitre prevalence (TGP) and urinary iodine concentrations (UIC) among the schoolchildren after USI was initiated. In 2004, a cross-sectional goitre survey was conducted; covering 140,758 schoolchildren aged 6 - 18 years were graded for goitre according to new WHO goitre classification system. Comparisons were made with district surveys conducted throughout most of the country during the 1980s and 90s. 131,941 salt samples from households were tested for iodine using rapid field test kits. UIC was determined spectrophotometrically using the ammonium persulfate digestion method in 4523 sub-sampled children. Results 83.6% (95% CI: 83.4 - 83.8) of salt samples tested positive for iodine. Whereas the TGP was about 25% on average in the earlier surveys, it was 6.9% (95%CI: 6.8-7.0) in 2004. The TGP for the younger children, 6-9 years old, was 4.2% (95%CI: 4.0-4.4), n = 41,965. In the 27 goitre-endemic districts, TGP decreased from 61% (1980s) to 12.3% (2004). The median UIC was 204 (95% CF: 192-215) μg/L. Only 25% of children had UIC <100 μg/L and 35% were ≥ 300 μg/L, indicating low and excess iodine intake, respectively. Conclusion Our study demonstrates a marked improvement in iodine nutrition in Tanzania, twelve years after the initiation of salt iodation programme. The challenge in sustaining IDD elimination in Tanzania is now two-fold: to better reach the areas with low coverage of iodated salt, and to reduce iodine intake in areas where it is excessive

  1. Increased risk of iodine deficiency with vegetarian nutrition.

    PubMed

    Remer, T; Neubert, A; Manz, F

    1999-01-01

    Observational studies primarily based on diet questionnaires or food records have reported that vegetarians can have a very low I intake. However, analytically ascertained data on the possible degree of I deficiency with this form of diet is lacking. Six healthy adult volunteers participated in the present controlled experimental diet study carried out in four separate 5 d diet periods. The study diets, normal, protein-rich, lactovegetarian, and repeat of the initial normal diet, were almost isoenergetic and contained no fish, sea food, iodized salt or processed foods fortified with I. During the last 48 h of each diet period two 24 h urine samples were obtained from each subject. I analyses were performed in the urine samples and in representative samples taken from all ingested diets. Urinary I excretion was significantly lower with the lactovegetarian diet (36.6 (SD 8.8) micrograms/d) than with the normal and the protein-rich diets (50.2 (SD 14.0) and 61.0 (SD 8.0) micrograms/d respectively). Accordingly, a markedly reduced I intake was confirmed analytically for the lactovegetarian diet (15.6 micrograms/d v. 35.2 and 44.5 micrograms/d respectively). Our results provide experimental confirmation of literature findings indicating that I supply is higher with non-vegetarian than with vegetarian diets. Specifically, the extremely low intake and urinary output of I as analytically determined for one exemplary vegetarian diet, demonstrate that dietary I may be limiting when strict forms of vegetarian dietary practices (no iodized salt, no I supplements) are followed. The present study is, therefore, the first diet-experiment-based pointer to the potential danger of I deficiency disorders due to strict forms of vegetarian nutrition, especially when fruits and vegetables grown in soils with low I levels are ingested.

  2. Drug-induced liver injury caused by iodine-131.

    PubMed

    Kim, Chei Won; Park, Ji Sun; Oh, Se Hwan; Park, Jae-Hyung; Shim, Hyun-Ik; Yoon, Jae Woong; Park, Jin Seok; Hong, Seong Bin; Kim, Jun Mi; Le, Trong Binh; Lee, Jin Woo

    2016-06-01

    Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well. PMID:27209646

  3. Drug-induced liver injury caused by iodine-131

    PubMed Central

    Kim, Chei Won; Park, Ji Sun; Oh, Se Hwan; Park, Jae-Hyung; Shim, Hyun-Ik; Yoon, Jae Woong; Park, Jin Seok; Hong, Seong Bin; Kim, Jun Mi; Le, Trong Binh; Lee, Jin Woo

    2016-01-01

    Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well. PMID:27209646

  4. Evaluation of Iodine Deficiency in Children with Attention Deficit/Hyperactivity Disorder

    PubMed Central

    Kanık Yüksek, Saliha; Aycan, Zehra; Öner, Özgür

    2016-01-01

    Objective: To investigate the incidence of iodine deficiency (ID) and its effects on mental function in children referred to the Dr. Sami Ulus Maternity and Children’s Training and Research Hospital with a prospective diagnosis of attention deficit/hyperactivity disorder (ADHD). Methods: The study was conducted on 89 children referred in the period from September 2009 to June 2010 with a diagnosis of ADHD. A questionnaire was given to all parents. Conners’ rating scales were applied to the parents (CPRS) and teachers (CTRS), and revised Wechsler intelligence scale for children (WISC-R) to the children. Serum thyroid-stimulating hormone, free triiodothyronine and free thyroxine, thyroglobulin, anti-thyroid peroxidase, anti-thyroglobulin, and urinary iodine levels were measured in all children. Results: Median age was 9.41±1.95 years, and 83.1% of subjects were male. The mean urinary iodine level of the children was 92.56±22.25 μg/L. ID was detected in 71.9% of subjects and all were mild ID. There was no significant relationship between urinary iodine levels with WISC-R subtest scores and CPRS. However, a significant association was found between urinary iodine levels and hyperactivity section of CTRS (p<0.05). Likewise, a significant relationship was found between learning disorder/mental retardation diagnosis and freedom subtest of WISC-R (p<0.05). Conclusion: This study highlights the effects of ID on comprehension, perception, attention, and learning. However, the results need to be supported by new randomized controlled trials. PMID:26758811

  5. Preparation and Characterization of Ultrarapidly Dissolving Orodispersible Films for Treating and Preventing Iodine Deficiency in the Pediatric Population.

    PubMed

    Rustemkyzy, Cholpon; Belton, Peter; Qi, Sheng

    2015-11-11

    Iodine deficiency is a public health problem that is easily prevented in many countries through having a salt iodization program. However, the World Health Organization (WHO) recommends that particular population groups including infants and young children have a sufficient level of daily iodine intake, while also reducing salt consumption in their diet. While many iodine supplements are available, swallowing tablet supplements is physically difficult for young children; thus, there is a need for the development of novel iodine delivery systems for pediatric patients. In this study a novel, ultrarapidly dissolving, nanofiber-based orodispersible film formulation containing iodine which is constructed from nanofibers was manufactured using an electrospinning technique. The potassium iodate (KIO3)-loaded poly(ethylene oxide) (PEO) fiber orodispersible films dissolve within seconds on wetting (applying on the tongue) without the need for the consumption of water. The electrospinning process and KIO3 loading did not alter the crystallinity and conformation of PEO. With high loading, KIO3 nanocrystals are present in the fibers. This formulation design allows easy administration of iodine for preventing childhood iodine deficiency. We have also described a novel and easy method for producing and harvesting nanocrystals of inorganic salts that can be potentially adopted for use in other relevant fields.

  6. Effects on school children of prophylaxis of mothers with iodized oil in an area of iodine deficiency.

    PubMed

    Fierro-Benitez, R; Cazar, R; Stanbury, J B; Rodriguez, P; Garces, F; Fierro-Renoy, F; Estrella, E

    1988-05-01

    The results of tests of intellectual and psychomotor performance and school performance in a group of school children from a rural impoverished and iodine deficient Andean community whose mothers received injections of iodinated oil prior to the end of the first trimester of pregnancy have been compared with results in children from a neighboring comparable community whose mothers had received no iodinated oil. Subjects between ages 8 and 15 were studied. Statistically significant differences were not observed between the two groups in tests of intellectual function, but children of mothers who had received iodinated oil performed better on tests of psychomotor maturation. The group whose mothers had received oil performed distinctly better when assessed in terms of school drop-out rates, grades achieved, grades repeated, and in overall performance as judged by teacher notes in school records. Performance of both groups on standard tests of intellectual and psychomotor function was lower than standard scores. This may be a result of social and cultural deprivation, the general malnutrition prevailing in the region or other unidentified factors. The improved scoring and school performance exhibited by the children of mothers who received iodinated oil underlines the importance of prophylaxis with iodine in iodine deficient regions as one important contributor to community development.

  7. Iodine deficiency in Belarusian children as a possible factor stimulating the irradiation of the thyroid gland during the Chernobyl catastrophe.

    PubMed Central

    Gembicki, M; Stozharov, A N; Arinchin, A N; Moschik, K V; Petrenko, S; Khmara, I M; Baverstock, K F

    1997-01-01

    Ten years after the Chernobyl nuclear plant catastrophe more than 500 children in Belarus are suffering from thyroid cancer. The major cause of the high incidence of thyroid cancer in children under 15 years of age appears to be contamination resulting from that catastrophe, mainly with isotopes of radioactive iodine. Another important factor may be iodine deficiency in the environment. A countrywide program for investigation of goiter prevalence and iodine deficiency has been established in the Republic of Belarus with the assistance of the European World Health Organization office. The program will oversee the examination of 11,000 children and adolescents 6 to 18 years of age from 30 schools in urban and rural areas. The results obtained in a group of 824 children and adolescents (the pilot phase) are typical for significant iodine deficiency and moderate goiter endemism. It is clear that the present situation does not completely reflect the situation that existed at the time of the Chernobyl catastrophe. However, data from epidemiologic studies conducted many years before the accident showed high goiter prevalence in the contaminated areas, indicating that the prevalence of iodine deficiency at the time of the catastrophe was similar to the present one or even greater. Such an assumption could lead to a better understanding of the thyroid pathologies that have been observed. PMID:9467069

  8. Physical, neuromotor and intellectual impairment in non-cretinous schoolchildren with iodine deficiency.

    PubMed

    Azizi, F; Kalani, H; Kimiagar, M; Ghazi, A; Sarshar, A; Nafarabadi, M; Rahbar, N; Noohi, S; Mohajer, M; Yassai, M

    1995-01-01

    Thyroid status and neurologic, psychometric and auditory functions were evaluated in presumably normal schoolchildren aged 6 to 16 years from three areas of iodine deficiency in Iran. The subjects from each area were identified as members of groups A, B or C. In group A there were retarded growth, high prevalence of visible goiter (93%), low T4 (39%) and high TSH (70%). In group B 66% had a visible goiter and 7% had high serum TSH. In group C visible goiter was present in 22% of the subjects but they had normal thyroid function. Urinary iodine excretion was low in all three groups. Head circumference was less in groups A and B, as compared to C. Pyramidal signs occurred in over half of the subjects in Group A (hyperreflexia in 39% and crossed adductor reflex in 29%). The glabellar sign was present in 50% of group A and 20% of group B. Forty-four percent of the subjects in group A and 17% in group B had hearing deficits as shown by audiometry. Psychomotor examination was performed using the Bender Gestalt test. A higher number of errors was evident in groups A and B their psychomotor age was below their chronological age. The results of the Raven test showed mild impairment of IQ in group A, with 55% having an IQ below 91 and 15% less than 70. The subjects in group B had lower IQ than group C, but higher than group A. There was a negative correlation between serum TSH and free thyroid indices and a positive correlation between TSH and the number of pyramidal signs. This study demonstrates that mild to moderate growth retardation and neurological, auditory and psychomotor impairments occur in apparently normal subjects residing in areas of iodine deficiency.

  9. Modelling protection behaviour towards micronutrient deficiencies: Case of iodine biofortified vegetable legumes as health intervention for school-going children

    PubMed Central

    De Steur, Hans; Gellynck, Xavier; Makokha, Anselimo

    2016-01-01

    BACKGROUND/OBJECTIVES Despite successes recorded in combating iodine deficiency, more than 2 billion people are still at risk of iodine deficiency disorders. Rural landlocked and mountainous areas of developing countries are the hardest hit, hence the need to explore and advance novel strategies such as biofortification. SUBJECTS/METHODS We evaluated adoption, purchase, and consumption of iodine biofortified vegetable legumes (IBVL) using the theory of protection motivations (PMT) integrated with an economic valuation technique. A total of 1,200 participants from three land-locked locations in East Africa were recruited via multi-stage cluster sampling, and data were collected using two, slightly distinct, questionnaires incorporating PMT constructs. The survey also elicited preferences for iodine biofortified foods when offered at a premium or discount. Determinants of protection motivations and preferences for iodine biofortified foods were assessed using path analysis modelling and two-limit Tobit regression, respectively. RESULTS Knowledge of iodine, iodine-health link, salt iodization, and biofortification was very low, albeit lower at the household level. Iodine and biofortification were not recognized as nutrient and novel approaches, respectively. On the other hand, severity, fear, occupation, knowledge, iodine status, household composition, and self-efficacy predicted the intention to consume biofortified foods at the household level; only vulnerability, self-efficacy, and location were the most crucial elements at the school level. In addition, results demonstrated a positive willingness-to-pay a premium or acceptance of a lesser discount for biofortification. Furthermore, preference towards iodine biofortified foods was a function of protection motivations, severity, vulnerability, fear, response efficacy, response cost, knowledge, iodine status, gender, age. and household head. CONCLUSIONS Results lend support for prevention of iodine deficiency in

  10. Iron-induced nickel deficiency in pecan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Economic loss due to nickel (Ni) deficiency can occur in horticultural and agronomic crops. This study assesses impact of excessive iron (Fe) on expression of Ni deficiency in pecan [Carya illinoinensis (Wangenh.) K. Koch]. Field and greenhouse experiments found Ni deficiency to be inducible by ei...

  11. Thyrotoxicosis induced by iodine contamination of food--a common unrecognised condition?

    PubMed

    Stewart, J C; Vidor, G I

    1976-02-14

    The incidence of thyrotoxicosis in northern Tasmania rose significantly in 1964, two years before an epidemic of iodine-induced thyrotoxicosis was precipitated by the addition of iodate to bread to prevent goitre. Each time older patients accounted for most of the increase. The 1964 increase was probably iodine-induced as the use of iodophor disinfectants on dairy farms, which causes iodine residues in milk, began in 1963 and a fall in the prevalence of goitre in young children suggested an increase in dietary iodine at about that time. A further small increase in thyrotoxicosis in 1971 may also have been iodine-induced as it followed an extension of the use of iodophors. Dietary iodine is rising substantially in many places because of high iodine levels in milk and the use of iodine compounds in automated bread making, and this may be causing unsuspected iodine-induced thyrotoxicosis. Dietary iodine should be monitored regularly and clinicans alerted to any rise. Contamination of common foods with iodine should be more strictly controlled.

  12. Iodine in diet

    MedlinePlus

    ... are good sources. Kelp is the most common vegetable-seafood that is a rich source of iodine. ... iodine deficiency is generally not a problem. Iodine poisoning is rare in the U.S. Very high intake ...

  13. Prevalence of iodine deficiency disorders among school children in Saudi Arabia: results of a national iodine nutrition study.

    PubMed

    Al-Dakheel, M H; Haridi, H K; Al-Bashir, B M; Al-Shingiti, A; Al-Shehri, S; Gassem, M A; Hussein, I

    2016-05-01

    This study aimed at establishing updated data on iodine nutrition among schoolchildren in Saudi Arabia. A cross-sectional cluster survey among schoolchildren aged 8-10 years was conducted during February-April 2012. Children were clinically examined for goitre, urine and household salt samples were collected to estimate urinary iodine concenteration (UIC) and iodine content in salt. The overall goitre prevalence at the national level among 4 016 children was 4.2%. The prevalence was < 5% in all regions of the country except southern region with a prevalence of 12.7%. The median UIC of 2224 samples was 133 μg/L, with 74.3% of the surveyed children with UIC ≥ 100 μg/L. Analysis of salt samples (n = 4242) revealed that 69.8% of households were consuming adequately iodized salt. The findings suggest iodine sufficiency at the national level, however southern region still has a goitre prevalence of mild degree severity and the proportion of households consuming adequately iodized salt is still below recommendations. PMID:27553396

  14. Prevalence of iodine deficiency disorders among school children in Saudi Arabia: results of a national iodine nutrition study.

    PubMed

    Al-Dakheel, M H; Haridi, H K; Al-Bashir, B M; Al-Shingiti, A; Al-Shehri, S; Gassem, M A; Hussein, I

    2016-08-18

    This study aimed at establishing updated data on iodine nutrition among schoolchildren in Saudi Arabia. A cross-sectional cluster survey among schoolchildren aged 8-10 years was conducted during February-April 2012. Children were clinically examined for goitre, urine and household salt samples were collected to estimate urinary iodine concenteration (UIC) and iodine content in salt. The overall goitre prevalence at the national level among 4 016 children was 4.2%. The prevalence was < 5% in all regions of the country except southern region with a prevalence of 12.7%. The median UIC of 2224 samples was 133 μg/L, with 74.3% of the surveyed children with UIC ≥ 100 μg/L. Analysis of salt samples (n = 4242) revealed that 69.8% of households were consuming adequately iodized salt. The findings suggest iodine sufficiency at the national level, however southern region still has a goitre prevalence of mild degree severity and the proportion of households consuming adequately iodized salt is still below recommendations.

  15. Laser-induced fluorescence method for on-line molecular isotopologues of iodine-127, iodine-129, iodine-131 detected in gaseous media using a tunable diode laser

    NASA Astrophysics Data System (ADS)

    Kireev, S. V.; Shnyrev, S. L.; Sobolevsky, I. V.

    2016-06-01

    The letter reports on the development of a laser-induced fluorescence method for on-line selective measurement of 127I2, 129I2, 131I2, 129I127I, 127I131I, 129I131I isotopologue concentrations in gaseous media. The method is based on the excitation of molecular iodine isotopologues’ fluorescence by tunable diode laser (632–637 nm) radiation at three or four wavelengths corresponding to the 127I2, 131I2, 129I127I, 129I131I absorption line centers. Boundary relations for concentrations of simultaneously measured iodine isotopologues is about 10‑5–10‑6.

  16. [An approach to a sanitary and social problem: urinary iodine excretion in pregnant women from a iodine deficient region].

    PubMed

    Olivares, Jorge L; Ortiz, Valeria A; Mayer, Marcos; Demaria, Cecilia I; Nancucheo, Ester; Cresto, Juan C

    2009-12-01

    The urinary iodine excretion (UIE) assay is an effective method to detect reduced iodine intake. UIE was measured in two different samples (morning and evening) from 121 pregnant women, with a turbid-metric method modified by Pino (normal value =150 ugl/1). Furthermore, thyroid function was evaluated in pregnant women with UIE <100 ug/l. From 121 pregnant women, the UIE was normal in 75 with similar morning and evening samples (morning: 305.2 +/- 7.0; evening: 319.2 +/- 8.8; p: NS). The UIE did no showed differences in different trimesters and in morning and evening samples. The UIE was low in 46 women (36.9%), without significant differences between morning and evening (morning: 88.12 +/- 5.07 microg/l; evening: 88.7 +/- 6.2 microg/l; p: NS). Normal or low UIE were not influenced by the age of pregnant women and 45% of pregnant women with UIE < 100 ug/l showed impaired thyroid function. Morning and evening study of UIE allowed us to detect a higher number of pregnant women with low iodine intake. This study let us to find thyroid function abnormalities likes a screening method, because in our state there is not a public screening program for gestational hypothyroidism.

  17. Injectant mole-fraction imaging in compressible mixing flows using planar laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Hartfield, Roy J., Jr.; Abbitt, John D., III; Mcdaniel, James C.

    1989-01-01

    A technique is described for imaging the injectant mole-fraction distribution in nonreacting compressible mixing flow fields. Planar fluorescence from iodine, seeded into air, is induced by a broadband argon-ion laser and collected using an intensified charge-injection-device array camera. The technique eliminates the thermodynamic dependence of the iodine fluorescence in the compressible flow field by taking the ratio of two images collected with identical thermodynamic flow conditions but different iodine seeding conditions.

  18. Defective neuromotor and cognitive ability in iodine-deficient schoolchildren of an endemic goiter region in Sicily.

    PubMed

    Vermiglio, F; Sidoti, M; Finocchiaro, M D; Battiato, S; Lo Presti, V P; Benvenga, S; Trimarchi, F

    1990-02-01

    Visual perceptual integrative motor ability was investigated in 719 6- to 12-yr-old, presumably normal, primary schoolchildren living in 2 iodine-deficient endemic goiter areas in Sicily, identified on the basis of the presence (area A) or absence (area B) of endemic cretinism, by administrating the Bender Gestalt test. All of these clinically euthyroid schoolchildren were also examined neurologically by an investigator unaware of the result of the Bender test. Ninety-nine (13.76%) schoolchildren were found to be defective by the Bender test; this prevalence was significantly higher than that (3.0%) found in an iodine-sufficient goiter-free control area (area C) lying at sea level (chi 2 = 36.25; P less than 0.000001). No difference in the prevalence of Bender abnormalities was apparent if the children were divided according to the area of provenience (area A, 14.4%; area B, 13.1%). A high percentage of children falling in the lower range of normality was found in both area A (15.5%) and area B (19.0%); this was significantly higher than that in area C (3.8%; chi 2 = 77.55; P less than 0.000001). Neuromuscular and neurosensorial abnormalities, including increased tendon reflexes, clonus of the foot, Babinski sign, minor disturbances in balance, and gait, and minor defects in hearing and speech, were apparent in 19.3% (area A) and 18.5% (area B) of the children. These disorders were significantly more frequent in defective children identified by the Bender test (33.3%) than in normal children (15.3%; (chi 2 = 17.29; P less than 0.00005). The general intellectual aptitude in Bender deficient subjects was evaluated by the Terman Merrill test and was found to be impaired in 95%, thus confirming the existence of an endemic cognitive deficiency (ECD), distinct from the endemic mental deficiency previously found in other endemic goiter, iodine-deficient areas. ECD seems to be epidemiologically independent of the existence of endemic cretinism. Further clinical auxological

  19. Change of iodine load and thyroid homeostasis induced by ammonium perchlorate in rats.

    PubMed

    Chen, Hong-Xia; Ding, Miao-Hong; Liu, Qin; Peng, Kai-Liang

    2014-10-01

    Ammonium perchlorate (AP), mainly used as solid propellants, was reported to interfere with homeostasis via competitive inhibition of iodide uptake. However, detailed mechanisms remain to be elucidated. In this study, AP was administered at 0, 130, 260 and 520 mg/kg every day to 24 male SD rats for 13 weeks. The concentrations of iodine in urine, serum thyroid hormones levels, total iodine, relative iodine and total protein, and malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activity in thyroid tissues were measured, respectively. Our results showed that high-dose perchlorate induced a significant increase in urinary iodine and serum thyroid stimulating hormone (TSH), with a decrease of total iodine and relative iodine content. Meanwhile, free thyroxine (FT4) was decreased and CAT activity was remarkably increased. Particularly, the CAT activity was increased in a dose-dependent manner. These results suggested that CAT might be enhanced to promote the synthesis of iodine, resulting in elevated urinary iodine level. Furthermore, these findings suggested that iodine in the urine and CAT activity in the thyroid might be used as biomarkers for exposure to AP, associated with thyroid hormone indicators such as TSH, FT4.

  20. Low dose oral iodized oil for control of iodine deficiency in children.

    PubMed

    Zimmermann, M; Adou, P; Torresani, T; Zeder, C; Hurrell, R

    2000-08-01

    In areas where iodized salt is not available, oral iodized oil is often used to correct I deficiency despite a lack of consensus on the optimal dose or duration of effect, particularly in children, a main target group. Annual doses ranging from 400 to 1000 mg have been advocated for school-age children. Because lower doses of iodized oil have been shown to be effective in treating I deficiency in adults, the aim of this study was to evaluate the efficacy and safety of a low dose of oral iodized oil in goitrous I-deficient children. Goitrous children (n 104, mean age 8.4 years, range 6-12 years, 47% female) received 0.4 ml oral iodized poppyseed-oil containing 200 mg I. Baseline measurements included I in spot urines (UI), serum thyroxine (T4), whole blood thyroid-stimulating hormone (TSH), and thyroid-gland volume using ultrasound. At 1, 5, 10, 15, 30 and 50 weeks post-intervention, UI, TSH and T4 were measured. At 10, 15, 30 and 50 weeks, thyroid-gland volume was remeasured. At 30 and 50 weeks the mean percentage change in thyroid volume from baseline was -35% and -41% respectively. The goitre rate fell to 38% at 30 weeks and 17% at 50 weeks. No child showed signs of I-induced hypo- or hyperthyroidism. UI remained significantly increased above baseline for the entire year (P < 0.001); the median UI at 50 weeks was 97 micrograms/l, at the World Health Organization cut-off value (100 micrograms/l) for I-deficiency disorders risk. In this group of goitrous children, an oral dose of 200 mg I as Lipiodol (Guerbert, Roissy CdG Cedex, France) was safe and effective for treating goitre and maintaining normal I status for at least 1 year.

  1. [Hypothyroid iodine deficiency struma in 2 siblings as a sequela of alternative nutrition].

    PubMed

    Krull, F; Ohlendorf, K

    1993-06-01

    Two siblings aged 4 and 7 years presented with a goitre and growth retardation. Laboratory data revealed hypothyroidism with elevated TSH, low T4 und T3, and a decreased urinary iodine excretion. Both children suffered from neurodermitis and because of that for already two years on a vegetarian diet free of any milk products; their nutrition contained sufficient calories but not enough iodine or vitamin B. PMID:8336743

  2. Iodine Supplementation: Usage "with a Grain of Salt".

    PubMed

    Prete, Alessandro; Paragliola, Rosa Maria; Corsello, Salvatore Maria

    2015-01-01

    Iodine supplementation through salt iodization is a worldwide, effective strategy for preventing iodine deficiency-related problems. Its safety and efficacy profile has been extensively investigated, and benefits far outweigh the potential iodine-induced risks. Moreover, iodine supplementation during pregnancy in order to avoid brain damage in the newborn is considered a mainstay of preventive medicine. Exposure to high amounts of iodine is actually well tolerated in most cases and can be unrecognized. Nevertheless, at-risk individuals may develop thyroid dysfunction even when they are exposed to increases in iodine intake universally considered as safe. Iodine-induced thyroid disorders include thyroid autoimmunity, thyrotoxicosis, iodine-induced goiter, and hypothyroidism. Moreover, a relationship between iodine intake and histotype distribution of differentiated thyroid cancer has been observed, with a progressive shift from follicular to papillary thyroid cancer. To date, evaluating iodine status in a clinical setting has limitations, and assessing the actual risk for each individual can be challenging, since it is influenced by personal history, genetics, and environmental factors. In conclusion, iodine supplementation programs need to be continued and strengthened, but iodine should be used "with a grain of salt," because a growing number of susceptible individuals will be exposed to the risk of developing iodine-induced thyroid disorders. PMID:25873950

  3. A mechanism for biologically induced iodine emissions from sea ice

    NASA Astrophysics Data System (ADS)

    Saiz-Lopez, A.; Blaszczak-Boxe, C. S.; Carpenter, L. J.

    2015-09-01

    Ground- and satellite-based measurements have reported high concentrations of iodine monoxide (IO) in coastal Antarctica. The sources of such a large iodine burden in the coastal Antarctic atmosphere remain unknown. We propose a mechanism for iodine release from sea ice based on the premise that micro-algae are the primary source of iodine emissions in this environment. The emissions are triggered by the biological production of iodide (I-) and hypoiodous acid (HOI) from micro-algae (contained within and underneath sea ice) and their diffusion through sea-ice brine channels, ultimately accumulating in a thin brine layer (BL) on the surface of sea ice. Prior to reaching the BL, the diffusion timescale of iodine within sea ice is depth-dependent. The BL is also a vital component of the proposed mechanism as it enhances the chemical kinetics of iodine-related reactions, which allows for the efficient release of iodine to the polar boundary layer. We suggest that iodine is released to the atmosphere via three possible pathways: (1) emitted from the BL and then transported throughout snow atop sea ice, from where it is released to the atmosphere; (2) released directly from the BL to the atmosphere in regions of sea ice that are not covered with snowpack; or (3) emitted to the atmosphere directly through fractures in the sea-ice pack. To investigate the proposed biology-ice-atmosphere coupling at coastal Antarctica we use a multiphase model that incorporates the transport of iodine species, via diffusion, at variable depths, within brine channels of sea ice. Model simulations were conducted to interpret observations of elevated springtime IO in the coastal Antarctic, around the Weddell Sea. While a lack of experimental and observational data adds uncertainty to the model predictions, the results nevertheless show that the levels of inorganic iodine (i.e. I2, IBr, ICl) released from sea ice through this mechanism could account for the observed IO concentrations during

  4. The epidemiology of iodine-deficiency disorders in relation to goitrogenic factors and thyroid-stimulating-hormone regulation.

    PubMed

    Thilly, C H; Swennen, B; Bourdoux, P; Ntambue, K; Moreno-Reyes, R; Gillies, J; Vanderpas, J B

    1993-02-01

    In children aged 5-7 y from goiter-endemic areas in Ubangi, Zaire, and Ntcheu, Malawi, mean serum thyroxin (T4) concentrations were 53 +/- 49 vs 81 +/- 33 nmol/L (P < 0.05), and thyroid-stimulating hormone (TSH) values were 24.3 +/- 9.6 vs 4.5 +/- 3.3 mU/L respectively (P < 0.01); mean urinary iodine concentrations were 0.14 +/- 0.02 vs 0.09 +/- 0.02 mumol/L, and mean thiocyanate concentrations were 0.33 +/- 0.05 vs 0.17 +/- 0.05 nmol/L, respectively (P < 0.05). Mean serum selenium concentrations were 0.343 +/- 0.176 mumol/L in Ubangi and 0.437 +/- 0.178 mumol/L in Ntcheu (P < 0.05). In two groups of 11 adolescent girls from Ubangi, the mean values for excretion of urinary iodine were 1.31 +/- 0.14 and 0.58 +/- 0.17 mumol/L (P < 0.05) after a meal of cassava or a control meal of rice, respectively. In euthyroid subjects from Ubangi, mean serum TSH for a given serum T4 was approximately twice as high for children aged < 15 y than for those aged 16-25 y. The high frequency of myxedematous cretins observed in Ubangi very probably result from both severe iodine and selenium deficiency together with thiocyanate overload. PMID:8427202

  5. Hair Iodine for Human Iodine Status Assessment

    PubMed Central

    Prejac, Juraj; Višnjević, Vjeran; Skalnaya, Margarita G.; Mimica, Ninoslav; Drmić, Stipe; Skalny, Anatoly V.

    2014-01-01

    Background: Today, human iodine deficiency is, after iron, the most common nutritional deficiency in developed European and underdeveloped third world countries. A current biological indicator of iodine status is urinary iodine, which reflects very recent iodine exposure; a long-term indicator of iodine status remains to be identified. Methods: We analyzed hair iodine in a prospective, observational, cross-sectional, and exploratory study involving 870 apparently healthy Croatians (270 men and 600 women). Hair iodine was analyzed with inductively coupled plasma mass spectrometry. Results: The hair iodine median was 0.499 μg/g, and was 0.482 and 0.508 μg/g for men and women respectively, suggesting no sex-related difference. We studied hair iodine uptake by analyzing the logistic sigmoid saturation curve of the median derivatives to assess iodine deficiency, adequacy, and excess. We estimated overt iodine deficiency to occur when hair iodine concentration was below 0.1–0.15 μg/g. Then there was a saturation range interval of about 0.1–2.0 μg/g where the deposition of iodine in the hair was linearly increasing (R2=0.994). Eventually, the sigmoid curve became saturated at about 2.0 μg/g and upward, suggesting excessive iodine exposure. Conclusion: Hair appears to be a valuable and robust biological indicator tissue for assessing long-term iodine status. We propose that an adequate iodine status corresponds with hair iodine uptake saturation of 0.565–0.739 μg/g (55–65%). PMID:24446669

  6. [Characteristics of hypothyroidism correction and lipid metabolism disorder in iodine deficiency].

    PubMed

    Voronych-Semchenko, N M

    2007-01-01

    The serum biochemical indexes (level of triiodthyronine, thyroxin, thyrothropic hormone of adenohypophysis, level of cholesterol, triglycerides) and the level of iodine excretion with urine in rats with hypothyrosis corrected by "Iodid-100" and along with excessive intake of chlorine and fluorine ions into the organism had been studied. It has been revealed that hypothyrosis has negative influence on lipid metabolism indexes. "Iodid- 100" usage stabilized hormonal and lipid status. Excessive intake of chlorine and fluorine ions by the organism decreased the effectiveness of iodine containing drugs.

  7. [The radioiodine test for the evaluation of iodine deficiency in the district of Karl-Marx-Stadt and in East Germany].

    PubMed

    Bauch, K; Weiss, O; Möckel, G; Gerlach, J; Seitz, W; Ulrich, F E; Dempe, A

    1981-10-01

    The values of the per cent 24 h radioiodine uptake in the GDR are above 60--70% and speak for a low alimentary intake of iodine or renal excretion of iodine below 40 micrograms J/d. Like the struma prevalences they show a tendency increasing from north to south and characterize the whole European situation of iodine deficiency including its decrease from west to east. The mean values of radioiodine uptake of 71.7 +/- 13.2% (n = 110) in euthyroids of the district of Karl-Marx-Stadt correspond to the iodine deficiency as it occurs approximately in the districts of Erfurt, Dresden, Munich or Freiburg/B. The alimentary iodine intake of 38.4 +/- 17.2 micrograms J/d and the renal iodine excretion of 29.9 +/- 16.1 micrograms J/d, calculated from the 24 h radioiodine accumulation values of 40 euthyroid persons by means of a mathematical model developed by Oddie and co-workers were low. The latter only slightly differed (P less than 0.05) from its chemically estimated excretion of iodine in the urine: 23.1 +/- 16.9 micrograms J/g creatinine (n = 73). Between the calculated and chemically estimated excretion of iodine there was a relatively strict correlation of r = 0.68 (n = 26; P less than 0.001). The introduction of an iodine prophylaxis is regarded as an urgent necessity. Later on a new estimation of the regional "normal values" is necessary for the per cent radioiodine uptake.

  8. An animal model of marginal iodine deficiency during development: The thyroid axis and neurodevelopmental outcome

    EPA Science Inventory

    Thyroid hormones (TH) are essential for brain development and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the neurological impairments associated with low level TH ...

  9. An animal model of marginal iodine deficiency during development: The thyroid axis and neurodevelopmental outcome. ##

    EPA Science Inventory

    Thyroid hormones (TH) are essential for brain development and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low...

  10. High prevalence of thyroid dysfunction and autoimmune thyroiditis in adolescents after elimination of iodine deficiency in the Eastern Black Sea Region of Turkey.

    PubMed

    Bastemir, Mehmet; Emral, Rifat; Erdogan, Gurbuz; Gullu, Sevim

    2006-12-01

    In the present study we evaluated the effects of iodine intake on the prevalence of thyroid dysfunction, autoimmunity, and goiter in two regions with different iodine status after two years of iodization in Turkey. In total 1733 adolescent subjects were enrolled into the study (993 from an iodine-sufficient area--the Eastern Black Sea Region (group 1) and 740 from an iodine-deficient area--Middle Anatolia (group 2)). We measured free thyroxine (FT(4)), thyrotropin (TSH), antithyroid peroxidase antibodies (Anti-TPO), antithyroglobulin antibodies (Anti-Tg), and urinary iodine (UI), and examined the thyroid gland by ultrasound. Median urinary iodine excretion was found to be significantly different in group 1 and group 2 (139 micro/l vs 61micro/l, p < 0.001). Hyperthyroidism was more frequent in group 1 (3.6% vs 0.7%; p < 0.001), but the hypothyroidism rate was similar between groups (1.8% vs 1.4 %; p>0.05). The percentage of anti-Tg positive subjects was found to be 17.6% in group 1 and 6.4% in group 2; that of anti-TPO positive subjects was 4.3% in group 1 and 1.5% in group 2. The prevalence of antithyroid antibody (anti-Tg and/or anti-TPO) positivity was significantly higher in group 1 than in group 2 (18.52% vs 6.62%; p < 0.001). Thyroid volumes of the hyperthyroid subjects in both groups were significantly higher than hypo- and euthyroid subjects. In conclusion, iodine supplementation in Turkey has resulted in the elimination of iodine deficiency in the Eastern Black Sea Region, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis and thyroid dysfunction.

  11. Investigation of laser-induced iodine fluorescence for the measurement of density in compressible flows

    NASA Technical Reports Server (NTRS)

    Mcdaniel, J. C., Jr.

    1982-01-01

    Laser induced fluorescence is an attractive nonintrusive approach for measuring molecular number density in compressible flows although this technique does not produce a signal that is directly related to the number density. Saturation and frequency detuned excitation are explored as means for minimizing the quenching effect using iodine as the molecular system because of its convenient absorption spectrum. Saturation experiments indicate that with available continuous wave laser sources of Gaussian transverse intensity distribution only partial saturation could be achieved in iodine at the pressures of interest in gas dynamics. Using a fluorescence lineshape theory, it is shown that for sufficiently large detuning of a narrow bandwidth laser from a molecular transition, the quenching can be cancelled by collisional broadening over a large range of pressures and temperatures. Experimental data obtained in a Mach 4.3 underexpanded jet of nitrogen seeded with iodine for various single mode argon laser detunings from a strong iodine transition at 5145 A are discussed.

  12. Geochemistry of trace elements in paddy (rice) soils of Sri Lanka--implications for iodine deficiency disorders (IDD).

    PubMed

    Chandrajith, Rohana; Dissanayake, Chandra B; Tobschall, Heinz J

    2005-02-01

    Iodine Deficiency Disorders (IDD) are a common health problem prevalent in the wet zone of Sri Lanka with a prevalence of >25% of the population. In comparison, in the dry zone of Sri Lanka IDD occurs in <10% of the population. Seventy soil samples from 14 villages selected on the basis of the incidence of goitre, were collected and analysed for 13 trace elements using ICP-MS. In order to identify any prevailing differences in antecedent chemical environments, soil samples from each pre-selected village were classified into three groups in terms of their geographical location. Among the elements investigated, the total soil concentrations of Rb, Sr, Ba, Mn and Co are lower in the wet zone of Kalutara. In contrast, total soil Rb, Sr, Ba and Mn contents are higher in the dry zone of Anuradhapura. Further soil total Mo and Nb levels are relatively similar in all pre-selected study locations. The high endemic goitre regions (IDD >25% of the population) show low levels of Rb, Sr, Ba, and Mn and higher levels of V, Cr, Co, Ni, Cu, Zn and Pb as compared with moderate and non-goitre areas. Factor analysis was used to exploit the correlation structure present in data and yielded three groups in all cases. This indicated that most transition group elements and iodine are associated with the Mn phase in the low IDD areas whereas iodine shows a high affinity for the organic phase in high IDD regions. The variable distribution of trace elements, therefore, must be due to differences in mobility and capacity for incorporation into the structure of secondary minerals or organic phases.

  13. Effects of Maternal Marginal Iodine Deficiency on Dendritic Morphology in the Hippocampal CA1 Pyramidal Neurons in Rat Offspring.

    PubMed

    Min, Hui; Wang, Yi; Dong, Jing; Wang, Yuan; Yu, Ye; Shan, Zhongyan; Xi, Qi; Teng, Weiping; Chen, Jie

    2016-06-01

    Although the salt iodization programmes are taken to control iodine deficiency (ID), some regions are still suffering from marginal ID. During pregnancy, marginal ID frequently leads to subtle insufficiency of thyroid hormones, characterized as low serum T4 levels. Therefore, the present research was to explore the effects of maternal marginal ID exposure on dendritic arbor growth in the hippocampal CA1 region and the underlying mechanisms. We established Wistar rat models with ID diet during pregnancy and lactation. The overall daily iodine intakes of the rats were estimated as 7.0, 5.0 and 1.5 μg/day in the control, marginal ID and severe ID groups, respectively. To study the morphological alterations of pyramidal neurons, Golgi-Cox procedure was conducted in the hippocampus. Sholl analyses demonstrated a slight decrease in the total length and branching numbers of basal dendrites on postnatal day (PN) 7, PN14 and PN21 in marginal ID group relative to the controls. However, there was no overt morphological change observed in apical dendrites. Immunofluorescence and Western blot analysis indicated that phosphorylation of MAP2, stathmin and JNK1 was down-regulated in marginal ID group. We speculate that the pups treated with maternal marginal ID subjected to subtle changes in dendritic growth of CA1 pyramidal neurons, which may be associated with the dysregulation of MAP2 and stathmin in a JNK1-dependent manner. PMID:27017219

  14. Pannexin 1 deficiency can induce hearing loss.

    PubMed

    Zhao, Hong-Bo; Zhu, Yan; Liang, Chun; Chen, Jin

    Gap junctions play a critical role in hearing. Connexin gap junction gene mutations can induce a high incidence of hearing loss. Pannexin (Panx) gene also encodes gap junction proteins in vertebrates. Panx1 is a predominant pannexin isoform and has extensive expression in the cochlea. Here, we report that deletion of Panx1 in the cochlea could produce a progressive hearing loss. The auditory brainstem response (ABR) recording showed that hearing loss was moderate to severe and severe at high-frequencies. Distortion product otoacoustic emission (DPOAE), which reflects the activity of active cochlear mechanics that can amply acoustic stimulation to enhance hearing sensitivity and frequency selectivity, was also reduced. We further found that Panx1 deficiency could activate Caspase-3 cell apoptotic pathway in the cochlea to cause hair cells and other types of cells degeneration. These data indicate that like connexins Panx1 deficiency can also induce hearing loss. These data also suggest that pannexins play important rather than redundant roles in the cochlea and hearing.

  15. Thyroid iodine content measured by x-ray fluorescence in amiodarone-induced thyrotoxicosis: concise communication

    SciTech Connect

    Leger, A.F.; Fragu, P.; Rougier, P.; Laurent, M.F.; Tubiana, M.; Savole, J.C.

    1983-07-01

    Iodine-induced thyrotoxicosis (IiT) is characterized by (a) a low radioiodine uptake, increased by exogenous TSH, and (b) a spontaneous evolution towards cure within a few months. An hypothetical pathogenesis of IiT is an initial inflation in the stores of thyroid hormones during iodine excess, followed by their sudden discharge into the circulation. Thyroid iodine content was measured by fluorescent scanning in 10 patients with amiodarone-induced thyrotoxicosis and in various control groups. Results were found to be high at the onset of the disease and to decrease during its course. The data agree with the hypothetical pathogenesis. Furthermore they may permit exclusion of a painless subacute thyroiditis, which is the main differential diagnosis of IiT.

  16. Electrophilic iodine(I) compounds induced semipinacol rearrangement via C-X bond cleavage.

    PubMed

    Tsuji, Nobuya; Kobayashi, Yusuke; Takemoto, Yoshiji

    2014-11-18

    Neutral electrophilic iodine(I) species proved to be efficient reagents for C-X bond cleavage of various cyclic and acyclic α-silyloxyhalides, and the induced desilylative semipinacol rearrangement provided the corresponding ketones in good yields. The reaction is operationally simple, and proceeds under mild conditions with good functional group compatibility. Mechanistic investigations, including computational studies, were also performed.

  17. Fast regioselective sulfonylation of pyridine/quinoline N-oxides induced by iodine.

    PubMed

    Wang, Ruijia; Zeng, Zebing; Chen, Chuang; Yi, Niannian; Jiang, Jun; Cao, Zhong; Deng, Wei; Xiang, Jiannan

    2016-06-21

    Fast sulfonylation of pyridine/quinoline N-oxides induced by iodine is demonstrated herein. The regioselective protocol occurs under metal-free conditions in a short reaction time (10 min), exhibiting high efficiency (up to 92% yield) and good compatibility (up to 33 examples). A gram-scale reaction was conducted with only a slight loss of production. PMID:27219641

  18. Some trends in the somatic development of children and adolescents under iodine-deficiency: materials from the Saratov region.

    PubMed

    Godina, Elena Z; Khomyakova, Irena A; Purundjan, Arsen L; Zadorozhnaya, Ludmila V; Stepanova, Alevtina V

    2005-07-01

    2,106 girls and 2,169 boys from 7 to 17 were investigated in 2002-2004 in three urban settlements of the Saratov region (Povolzhje area): the town of Khvalynsk, population 15,000, with a low level of industrialization; the city of Balakovo, population 220,000, highly industrialized and with a nuclear power station; and the city of Saratov, population around 1,000,000 a regional capital, and also highly industrialized. The whole area, particularly the location of Khvalynsk, is also characterized by iodine deficiency (iodine concentration is 0.78 mkg/kg v. normal values of 5-7 mkg/kg). The program included about 30 anthropometric measurements, evaluation of developmental stages of secondary sexual characteristics, and information on menarcheal age by the status quo method. Information on parental occupation and education, as well as number of children per family was collected by questionnaire. For the analysis all the data were standardized, and further comparisons were made irrespective of age groups. The significance of differences was assessed by one-way ANOVA. For height, weight and chest circumference there are significant differences among the three populations (p < 0.001), with Khvalynsk children being the smallest in body height and weight. However, in chest circumference they are close to or even bigger (girls) than Balakovo children. The children from Khvalynsk are characterized by the lowest values for subcutaneous fat layer, both on the trunk and extremities. For the age of menarche, Khvalynsk girls have the highest values: 13 years 5 months (13.42). In Balakovo and Saratov, the corresponding figures are identical: 13 years 2 months (13.17). Secular changes in Khvalynsk and Saratov children are discussed as compared to the literature.

  19. Planar temperature measurement in compressible flows using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Hartfield, Roy J., Jr.; Hollo, Steven D.; Mcdaniel, James C.

    1991-01-01

    A laser-induced iodine fluorescence technique that is suitable for the planar measurement of temperature in cold nonreacting compressible air flows is investigated analytically and demonstrated in a known flow field. The technique is based on the temperature dependence of the broadband fluorescence from iodine excited by the 514-nm line of an argon-ion laser. Temperatures ranging from 165 to 245 K were measured in the calibration flow field. This technique makes complete, spatially resolved surveys of temperature practical in highly three-dimensional, low-temperature compressible flows.

  20. Modelling of iodine-induced stress corrosion cracking in CANDU fuel

    NASA Astrophysics Data System (ADS)

    Lewis, B. J.; Thompson, W. T.; Kleczek, M. R.; Shaheen, K.; Juhas, M.; Iglesias, F. C.

    2011-01-01

    Iodine-induced stress corrosion cracking (I-SCC) is a recognized factor for fuel-element failure in the operation of nuclear reactors requiring the implementation of mitigation measures. I-SCC is believed to depend on certain factors such as iodine concentration, oxide layer type and thickness on the fuel sheath, irradiation history, metallurgical parameters related to sheath like texture and microstructure, and the mechanical properties of zirconium alloys. This work details the development of a thermodynamics and mechanistic treatment accounting for the iodine chemistry and kinetics in the fuel-to-sheath gap and its influence on I-SCC phenomena. The governing transport equations for the model are solved with a finite-element technique using the COMSOL Multiphysics® commercial software platform. Based on this analysis, this study also proposes potential remedies for I-SCC.

  1. The prevalence of goiter and hypothyroidism among school children 6 years after introduction of a mandatory salt iodination program in a severely iodine-deficient area of the West Black Sea region of Turkey.

    PubMed

    Uzun, Hakan; Gozkaya, Sercin; Yesildal, Nuray; Okur, Mesut; Arslanoglu, İlknur; Kocabay, Kenan; Senses, Dursun A

    2014-08-01

    The objective of the current study was to determine the prevalence and the degree of iodine deficiency after mandatory salt iodization in Yığılca's school-aged children. A total of 806 school children aged 6-19 years were evaluated. The prevalence of goiter in children aged 6-12 and 13-19 years was 20.3 and 23.8%, respectively. The prevalence of hypothyroidism in children aged 6-12 and 13-19 years was 10.4 and 18.9%, respectively. The median serum free tetraiodothyronine (fT4) levels in children aged 6-12 and 13-19-years were 1.16 ng/dL and 0.91 ng/dL, respectively. The median urinary iodine concentration levels in children aged 6-12 and 13-19 years were 83 µg/l and 78 µg/l, respectively. The frequency of autoimmune thyroid disease was 2.1% in Yığılca's SAC. Goiter and iodine deficiency problems remain in rural areas of the West Black Sea Region of Turkey.

  2. Tomato fruits: a good target for iodine biofortification

    PubMed Central

    Kiferle, Claudia; Gonzali, Silvia; Holwerda, Harmen T.; Ibaceta, Rodrigo Real; Perata, Pierdomenico

    2013-01-01

    Iodine is a trace element that is fundamental for human health: its deficiency affects about two billion people worldwide. Fruits and vegetables are usually poor sources of iodine; however, plants can accumulate iodine if it is either present or exogenously administered to the soil. The biofortification of crops with iodine has therefore been proposed as a strategy for improving human nutrition. A greenhouse pot experiment was carried out to evaluate the possibility of biofortifying tomato fruits with iodine. Increasing concentrations of iodine supplied as KI or KIO3 were administered to plants as root treatments and the iodine accumulation in fruits was measured. The influences of the soil organic matter content or the nitrate level in the nutritive solution were analyzed. Finally, yield and qualitative properties of the biofortified tomatoes were considered, as well as the possible influence of fruit storage and processing on the iodine content. Results showed that the use of both the iodized salts induced a significant increase in the fruit’s iodine content in doses that did not affect plant growth and development. The final levels ranged from a few mg up to 10 mg iodine kg - 1 fruit fresh weight and are more than adequate for a biofortification program, since 150 μg iodine per day is the recommended dietary allowance for adults. In general, the iodine treatments scarcely affected fruit appearance and quality, even with the highest concentrations applied. In contrast, the use of KI in plants fertilized with low doses of nitrate induced moderate phytotoxicity symptoms. Organic matter-rich soils improved the plant’s health and production, with only mild reductions in iodine stored in the fruits. Finally, a short period of storage at room temperature or a 30-min boiling treatment did not reduce the iodine content in the fruits, if the peel was maintained. All these results suggest that tomato is a particularly suitable crop for iodine biofortification programs

  3. The ameliorating effects of vitamin E on hepatic antioxidant system and xenobiotic-metabolizing enzymes in fenvalerate-exposed iodine-deficient rats.

    PubMed

    Kocer-Gumusel, Belma; Erkekoglu, Pinar; Caglayan, Aydan; Hincal, Filiz

    2016-01-01

    This study investigated the effects of vitamin E (VE) on hepatic antioxidant system and drug-metabolizing enzymes in fenvalerate (FEN)-exposed iodine-deficient (ID) Wistar rats. ID was produced by perchlorate containing drinking water. VE was introduced by a loading dose of 100 mg/kg/d, i.g. for the first three days in the last week of feeding period; then with a single maintenance dose of 40 mg/kg on the 4th day. During last week, FEN groups (F) received 100 mg/kg/d, i.p. FEN. VE alone did not significantly affect thyroid hormones and antioxidant parameters; however, significantly increased total cytochrome P450 (38%) and cytochrome b5 levels (36%). In all ID groups, plasma thyroid-stimulating hormone (TSH) levels increased markedly, but remained at control level in vitamin E plus FEN receiving iodine-deficient group (IDVF) group. Glutathione peroxidase activity showed marked increases in F (19%) and FEN-exposed iodine-deficient group (IDF, 48%) groups. FEN treatment significantly increased total cytochrome P450 (28%) and thiobarbituric acid reactive substance levels (36%), as well as 7-ethoxyresorufin O-deethylase (120%), 7-penthoxyresorufin O-deethylase (139%) and glutathione S-transferase (15%) activities and decreased total glutathione concentrations (28%) versus control. Overall results suggest that vitamin E has ameliorating effects on the measured parameters in ID and/or FEN exposure.

  4. Velocity Field Measurements in Rarefied, Hypersonic Flows of Nitrogen Using Laser-Induced Fluorescence of Iodine

    NASA Astrophysics Data System (ADS)

    Cecil, Eric

    Velocity fields are measured in the shock layer and boundary layer on a plate with a cylindrical fin immersed in a hypersonic, free jet of nitrogen, using laser-induced fluorescence (LIF) of iodine. A sheet beam from a single-mode argon laser at 514 nm is used to excite hyperfine components of the P(13), R(15) and P(48), P(103) blended rotational-vibrational lines in the B-X electronic transition for iodine seeded in the flow. The Doppler broadening and shift of these lines, and the relative rotational line strengths are determined for excitation spectra recorded in a planar grid. Using this measurement technique, estimates for iodine of the mass velocity component and kinetic temperature of translation in the direction of laser propagation, rotational temperature, and relative number density are determined at each point. Sectional planes of the flow over the body are investigated at a spatial resolution on the scale of the molecular mean-free-path in the free jet near the plate leading edge. Two directions within each plane are examined, to determine the velocity vector and to investigate translational non-equilibrium. Predictions from two direct simulation Monte Carlo computations of the flow are compared with the measurements. Large values of slip velocity and temperature jump at the plate surface are observed for iodine. Measurements and DSMC predictions indicate strong translational non-equilibrium effects for the iodine in the shock wave and the thick boundary layer on the plate, and are qualitatively consistent with a bimodal velocity distribution function. As a consequence of the ratio of molecular masses, the translational non-equilibrium of iodine is much greater than for nitrogen.

  5. Copper deficiency potentiates ethanol induced liver damage

    SciTech Connect

    Zidenberg-Cherr, S.; Han, B.; Graham, T.W.; Keen, C.L. )

    1992-02-26

    Copper sufficient (+Cu) and deficient ({minus}Cu) rats were fed liquid diets with EtOH or dextrose at 36% of kcals for 2 mo. Consumption of either the {minus}Cu diet or EtOH resulted in lower liver CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) activities were lowest in EtOH/{minus}Cu rats; being 20% and 50% of control values, respectively. Ethanol resulted in higher MnSOD activity in +Cu and {minus}Cu rats. Low Cu intake as well as EtOH resulted in lower mitochondrial (Mit) TBARS relative to controls. TBARS were lowest in Mit from EtOH/{minus}Cu rats. Microsomal (Micro) TBARS were lower in {minus}Cu and EtOH-fed rats than in controls. The peroxidizability index (PI) was calculated as an index of substrate availability for lipid peroxidation. Ethanol feeding resulted in lower PI's in Mit and Micro than measured in non-EtOH rats. There was a positive correlation between Micro PI's and TBARS. These results show that despite reductions in components of antioxidant defense, compensatory mechanism arise resulting in reduction in peroxidation targets and/or an increase in alternate free radical quenching factors. Histological examination demonstrated increased portal and intralobular connective tissue and cell necrosis in EtOH/{minus}Cu rats, suggesting that Cu may be a critical modulator of EtOH induced tissue damage.

  6. Iodine supplementation in the newborn.

    PubMed

    Ghirri, Paolo; Lunardi, Sara; Boldrini, Antonio

    2014-01-01

    Iodine deficiency can be defined as the world's greatest single cause of preventable brain damage. Fetal and neonatal hypothyroidism, caused by iodine deficiency can be prevented prior to conception and then during pregnancy and lactation when an adequate iodine supplementation is ensured. Extremely low birth weight preterm babies risk having a negative iodine balance status in the first weeks of life, exacerbating the hypothyroxinaemia of the prematurity. It is important to ensure that these babies are provided with an adequate iodine intake from the first days of life. Mothers and newborns should avoid environmental iodine excess during pregnancy or lactation.

  7. Assessment of iodine deficiency and goitre incidence in parts of Yewa Area of Ogun State, Southwestern Nigeria.

    PubMed

    Gbadebo, A M; Oyesanya, T M

    2005-09-01

    This study was carried out to determine the occurrence, prevalence and contributing factors to the incidence of goitre in Yewa north local government area of Ogun state, southwestern Nigeria. To achieve these objectives, soil, water, and cassava tubers were collected from four villages -- Igbogila, Egua, Sawonjo and Imoto and from Lagos (about 250 m to the ocean) as a reference location, in order to determine their iodine concentrations. The results of the analyses indicated a soil mean iodine range of 2.1-5.8 microg g(-1); a cassava mean iodine value of 2.3-3.5 mug g(-1) and a drinking water mean iodine value of generally <1.0 microg L(-1) in all the four villages. These values of iodine in soil and water of the four villages are considered low when compared with the soil iodine value of 7.4 microg g(-1) and water iodine value of 6.1 microg L(-1) obtained from Lagos. The limestone unit of the study area remains an inhibiting factor in the bioavailability of the iodine because of its alkalinity. Statistical analysis has shown that there was significant difference between iodine concentration in the soils and the drinking water, and a correlation between the soil iodine and organic matter content at p < 0.05. The correlation between soil iodine and granulometric fractions occurred at p < 0.01. Potential goitrogens in the commonly consumed cassava products might also have contributed to the prevalence of goitre in the study area. Both the females and the adults (i.e., less mobile groups) were found to be vulnerable to goitre development in these villages. PMID:16237605

  8. Early effects of iodine deficiency on radial glial cells of the hippocampus of the rat fetus. A model of neurological cretinism.

    PubMed Central

    Martínez-Galán, J R; Pedraza, P; Santacana, M; Escobar del Ray, F; Morreale de Escobar, G; Ruiz-Marcos, A

    1997-01-01

    The most severe brain damage associated with thyroid dysfunction during development is observed in neurological cretins from areas with marked iodine deficiency. The damage is irreversible by birth and related to maternal hypothyroxinemia before mid gestation. However, direct evidence of this etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine content (LID), or LID supplemented with KI. Other rats were fed the breeding diet with a normal iodine content plus a goitrogen, methimazole (MMI). The concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were determined in the brain of 21-d-old fetuses. The proportion of radial glial cell fibers expressing nestin and glial fibrillary acidic protein was determined in the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the LID and MMI fetuses, as compared to their respective controls. The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams. These results show impaired maturation of cells involved in neuronal migration in the hippocampus, a region known to be affected in cretinism, at a stage of development equivalent to mid gestation in humans. The impairment is related to fetal cerebral thyroid hormone deficiency during a period of development when maternal thyroxinemia is believed to play an important role. PMID:9169500

  9. Tob deficiency superenhances osteoblastic activity after ovariectomy to block estrogen deficiency-induced osteoporosis

    PubMed Central

    Usui, Michihiko; Yoshida, Yutaka; Tsuji, Kunikazu; Oikawa, Kaoru; Miyazono, Kohei; Ishikawa, Isao; Yamamoto, Tadashi; Nifuji, Akira; Noda, Masaki

    2004-01-01

    Tob (transducer of erbB2) is a member of antiproliferative family proteins and acts as a bone morphogenic protein inhibitor as well as a suppressor of proliferation in T cells, which have been implicated in postmenopausal bone loss. To determine the effect of Tob deficiency on estrogen deficiency-induced bone loss, we analyzed bone metabolism after ovariectomy or sham operation in Tob-deficient mice. Ovariectomy in WT mice decreased trabecular bone volume and bone mineral density (BMD) as expected. In Tob-deficient mice, ovariectomy reduced bone volume and BMD. However, even after ovariectomy, both trabecular bone volume and BMD levels in Tob-deficient bone were comparable to those in sham-operated WT bones. Bone formation parameters (mineral apposition rate and bone formation rate) in the ovariectomized Tob-deficient mice were significantly higher than those in the ovariectomized WT mice. In contrast, the ovariectomy-induced increase in the bone resorption parameters, osteoclast surface, and osteoclast number was similar between Tob-deficient mice and WT mice. Furthermore, in ex vivo nodule formation assay, ovariectomy-induced enhancement of nodule formation was significantly higher in the bone marrow cells from Tob-deficient mice than in the bone marrow cells from ovariectomized WT mice. Both Tob and estrogen signalings converge at bone morphogenic protein activation of alkaline phosphatase and GCCG-reporter gene expression in osteoblasts, revealing interaction between the two signals. These data indicate that Tob deficiency prevents ovariectomy-induced bone loss through the superenhancement of osteoblastic activities in bone and that this results in further augmentation in the bone formation rate and the mineral apposition rate after ovariectomy in vivo. PMID:15100414

  10. Upregulation of TSHR, TTF-1, and PAX8 in Nodular Goiter Is Associated with Iodine Deficiency in the Follicular Lumen

    PubMed Central

    Chen, Lijun; Liang, Bo; Cai, Huiyao; Cai, Qingyan; Shi, Yaxiong

    2016-01-01

    Objective. It has been testified that iodine regulates thyroid function by controlling thyroid-restricted genes expression and is closely related to diffuse goiter and thyroid dysfunction. However, the effects of follicular lumen iodine, the main form of iodine reserve in the body, on thyroid-restricted genes in nodular goiter are poorly understood. In this study, correlations between follicular lumen iodine and the expressions of thyroid stimulating hormone receptor (TSHR), its transcription factors TTF-1, and PAX8 in nodular goiter were investigated. Patients. In this study, 30 resection specimens clinically histopathologically confirmed to have nodular goiter and 30 normal thyroid specimens from adjacent tissues of nodular goiter are used. Measurement. Western blot immunohistochemistry was performed to assay TSHR, TTF-1, and PAX8 in thyrocytes of nodular goiter as well as in extranodular normal thyroid tissues. Meanwhile, follicular lumen iodine of both nodular goiter and extranodular normal thyroid tissues was detected as well. Results. The TSHR, TTF-1, and PAX8 in nodular goiter were significantly higher than those in the controls. The iodine content in nodular goiter was significantly lower than those in control tissues. Conclusion. Upregulation of TSHR, TTF-1, and PAX8 is associated with low follicular lumen iodine content in nodular goiter. PMID:27525008

  11. Antimicrobial fabric adsorbed iodine produced by radiation-induced graft polymerization

    NASA Astrophysics Data System (ADS)

    Aoki, Shoji; Fujiwara, Kunio; Sugo, Takanobu; Suzuki, Koichi

    2013-03-01

    Antimicrobial fabric was synthesized by radiation-induced graft polymerization of N-vinyl pyrrolidone onto polyolefine nonwoven fabric and subsequent adsorption of iodine. In response of the huge request for the antimicrobial material applied to face masks for swine flu in 2009, operation procedure of continuous radiation-induced graft polymerization apparatus was improved. The improved grafting production per week increased 3.8 times compared to the production by former operation procedure. Shipped antimicrobial fabric had reached 130,000 m2 from June until December, 2009.

  12. [PECULIARITIES OF THE COURSE OF PREGNANCY, THE IMPLICATIONS OF DELIVERY IN WOMEN WITH PREECLAMPSIA IN THE CONDITIONS OF NATURAL IODINE DEFICIENCY].

    PubMed

    Fedynchuk, G V; Maliar, V A

    2015-01-01

    The level of preeclampsia in 2.2 times higher in mountain regions as compared with lowland. In the presence of concomitant pathology of the thyroid gland on a background of natural iodine deficiency in pregnancy complicated with recurrent pregnancy loss in 2.8 times more primary placental insufficiency in 3.6 times, oligohydramnios 1.5 times, premature rupture of the amniotic fluid in 1.9 times, anemia, preeclampsia develops at earlier periods of gestation and more difficult to correct medication, in most cases becomes more severe.

  13. False-Positive Radioactive Iodine Uptake Mimicking Miliary Lung Metastases in a Patient Affected by Papillary Thyroid Cancer and IgA Deficiency.

    PubMed

    Demidowich, Andrew Paul; Kundu, Amartya; Reynolds, James C; Celi, Francesco S

    2016-09-01

    A 42-year-old female with immunoglobulin A deficiency and recurrent sinopulmonary infections underwent thyroidectomy for papillary thyroid cancer (PTC). Follow-up (123)I scintigraphy demonstrated diffuse pulmonary uptake, suggesting metastatic disease. However, subsequent pathologic, biochemical and radiographic testing proved that she was in fact disease free, and the initial (123)I pulmonary uptake was identified as a false positive. Inflammatory conditions may rarely cause iodine uptake in non-thyroidal tissues due to local retention, organification, and/or immunologic utilization. To avoid exposing patients to unnecessary treatments, it is critical for clinicians to recognize that comorbid pulmonary conditions may mimic metastatic PTC on radioiodine scintigraphy. PMID:27540434

  14. Iodine Excess as an Environmental Risk Factor for Autoimmune Thyroid Disease

    PubMed Central

    Luo, Yuqian; Kawashima, Akira; Ishido, Yuko; Yoshihara, Aya; Oda, Kenzaburo; Hiroi, Naoki; Ito, Tetsuhide; Ishii, Norihisa; Suzuki, Koichi

    2014-01-01

    The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more frequent occurrence than iodine deficiency. Iodine excess is a precipitating environmental factor in the development of autoimmune thyroid disease. Excessive amounts of iodide have been linked to the development of autoimmune thyroiditis in humans and animals, while intrathyroidal depletion of iodine prevents disease in animal strains susceptible to severe thyroiditis. Although the mechanisms by which iodide induces thyroiditis are still unclear, several mechanisms have been proposed: (1) excess iodine induces the production of cytokines and chemokines that can recruit immunocompetent cells to the thyroid; (2) processing excess iodine in thyroid epithelial cells may result in elevated levels of oxidative stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3) iodine incorporation in the protein chain of thyroglobulin may augment the antigenicity of this molecule. This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease. PMID:25050783

  15. Consequences of excess iodine

    PubMed Central

    Leung, Angela M.; Braverman, Lewis E.

    2014-01-01

    Iodine is a micronutrient that is essential for the production of thyroid hormones. The primary source of iodine is the diet via consumption of foods that have been fortified with iodine, including salt, dairy products and bread, or that are naturally abundant in the micronutrient, such as seafood. Recommended daily iodine intake is 150 μg in adults who are not pregnant or lactating. Ingestion of iodine or exposure above this threshold is generally well-tolerated. However, in certain susceptible individuals, including those with pre-existing thyroid disease, the elderly, fetuses and neonates, or patients with other risk factors, the risk of developing iodine-induced thyroid dysfunction might be increased. Hypothyroidism or hyperthyroidism as a result of supraphysiologic iodine exposure might be either subclinical or overt, and the source of the excess iodine might not be readily apparent. PMID:24342882

  16. Consequences of excess iodine.

    PubMed

    Leung, Angela M; Braverman, Lewis E

    2014-03-01

    Iodine is a micronutrient that is essential for the production of thyroid hormones. The primary source of iodine is the diet via consumption of foods that have been fortified with iodine, including salt, dairy products and bread, or that are naturally abundant in the micronutrient, such as seafood. Recommended daily iodine intake is 150 µg in adults who are not pregnant or lactating. Ingestion of iodine or exposure above this threshold is generally well-tolerated. However, in certain susceptible individuals, including those with pre-existing thyroid disease, the elderly, fetuses and neonates, or patients with other risk factors, the risk of developing iodine-induced thyroid dysfunction might be increased. Hypothyroidism or hyperthyroidism as a result of supraphysiologic iodine exposure might be either subclinical or overt, and the source of the excess iodine might not be readily apparent.

  17. Quantitative characterization of a nonreacting, supersonic combustor flowfield using unified, laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Fletcher, D. G.; Mcdaniel, J. C.

    1989-01-01

    A calibrated, nonintrusive optical technique, laser-induced iodine fluorescence (LIIF) was used to quantify the steady, compressible flowfield of a nonreacting, supersonic combustor. The combustor was configured with single and staged, transverse-air injection into a supersonic-air freestream behind a rearward-facing step. Pressure, temperature, two-velocity components, and injectant mole fraction were measured with high spatial resolution in the three-dimensional flowfields. These experimental results provide a benchmark set of data for validation of computational fluid dynamic (CFD) codes being developed to model supersonic combustor flowfields.

  18. Reference intervals of thyroid hormones in a previously iodine-deficient but presently more than adequate area of Western China: a population-based survey.

    PubMed

    Cai, Jing; Fang, Yujie; Jing, Da; Xu, Shaoyong; Ming, Jie; Gao, Bin; Shen, Han; Zhang, Rong; Ji, Qiuhe

    2016-04-25

    The aim of our study is to establish the reference intervals (RIs) of thyroid hormones in a previously iodine-deficient area but presently more than iodine-adequate area of Western China, and also to investigate the factors which affect thyroid function. The cross-sectional study conducted in Xi'an, was based on 2007-2008 China National Diabetes and Metabolic Disorders Survey. Among 1286 participating adults, 717 were finally included as reference population. Thyrotropin (TSH), total triiodothyronine (T3), free triiodothyronine (FT3), total thyroxine (T4), free thyroxine (FT4), thyroperoxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were measured. Thyroid ultrasound examination was also performed. The present study established the new RIs of serum TSH (0.43-5.51 mIU/L), FT4 (11.0-20.4 pmol/L), FT3 (3.63-5.73 pmol/L), T4 (67.8-157 mmol/L) and T3 (1.08-2.20 mmol/L), which were different from the data provided by the manufacturers. Significant differences among all the age groups were observed in FT3, but neither in TSH nor in FT4. The TSH levels in adults with pathologic ultrasonography results or positive thyroid autoantibody were significantly higher than those in reference adults. Our present results provide valuable references for the diagnosis of thyroid diseases in population of Western China. Considering that most inland areas of China have faced the challenge of the transition from iodine deficiency to adequacy or more than adequacy, we recommend physicians utilize our RIs to determine thyroid diseases in the similar areas with Xi'an in China. PMID:26842591

  19. Reference intervals of thyroid hormones in a previously iodine-deficient but presently more than adequate area of Western China: a population-based survey.

    PubMed

    Cai, Jing; Fang, Yujie; Jing, Da; Xu, Shaoyong; Ming, Jie; Gao, Bin; Shen, Han; Zhang, Rong; Ji, Qiuhe

    2016-04-25

    The aim of our study is to establish the reference intervals (RIs) of thyroid hormones in a previously iodine-deficient area but presently more than iodine-adequate area of Western China, and also to investigate the factors which affect thyroid function. The cross-sectional study conducted in Xi'an, was based on 2007-2008 China National Diabetes and Metabolic Disorders Survey. Among 1286 participating adults, 717 were finally included as reference population. Thyrotropin (TSH), total triiodothyronine (T3), free triiodothyronine (FT3), total thyroxine (T4), free thyroxine (FT4), thyroperoxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were measured. Thyroid ultrasound examination was also performed. The present study established the new RIs of serum TSH (0.43-5.51 mIU/L), FT4 (11.0-20.4 pmol/L), FT3 (3.63-5.73 pmol/L), T4 (67.8-157 mmol/L) and T3 (1.08-2.20 mmol/L), which were different from the data provided by the manufacturers. Significant differences among all the age groups were observed in FT3, but neither in TSH nor in FT4. The TSH levels in adults with pathologic ultrasonography results or positive thyroid autoantibody were significantly higher than those in reference adults. Our present results provide valuable references for the diagnosis of thyroid diseases in population of Western China. Considering that most inland areas of China have faced the challenge of the transition from iodine deficiency to adequacy or more than adequacy, we recommend physicians utilize our RIs to determine thyroid diseases in the similar areas with Xi'an in China.

  20. Opioid-induced androgen deficiency (OPIAD).

    PubMed

    Smith, Howard S; Elliott, Jennifer A

    2012-07-01

    Opioid therapy is one of the most effective forms of analgesia currently in use. In the past few decades, the use of opioids as a long-term treatment for chronic pain has increased dramatically. Accompanying this upsurge in the use of long-term opioid therapy has been an increase in the occurrence of opioid associated endocrinopathy, most commonly manifested as an androgen deficiency and therefore referred to as opioid associated androgen deficiency (OPIAD). This syndrome is characterized by the presence of inappropriately low levels of gonadotropins (follicle stimulating hormone and luteinizing hormone) leading to inadequate production of sex hormones, particularly testosterone. Symptoms that may manifest in patients with OPIAD include reduced libido, erectile dysfunction, fatigue, hot flashes, and depression. Physical findings may include reduced facial and body hair, anemia, decreased muscle mass, weight gain, and osteopenia or osteoporosis. Additionally, both men and women with OPIAD may suffer from infertility. While the literature regarding OPIAD remains limited, it is apparent that OPIAD is becoming increasingly prevalent among chronic opioid consumers but often goes unrecognized. OPIAD can have a significant negative impact on the the quality of life of opioid users, and clinicians should anticipate the potential for its occurrence whenever long-term opioid prescribing is undertaken. Once diagnosed, treatment for OPIAD may be offered utilizing a number of androgen replacement therapy options including a variety of testosterone preparations and, for female patients with OPIAD, dehydroepiandrosterone (DHEA) supplementation. Follow-up evaluation of patients receiving androgen replacement therapy should include a review of any unresolved symptoms of hypogonadism, laboratory evaluation, and surveillance for potential adverse effects of androgen replacement therapy including prostate disease in males.: PMID:22786453

  1. A unified planar measurement technique for compressible flows using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Hartfield, Roy J., Jr.; Hollo, Steven D.; Mcdaniel, James C.

    1992-01-01

    A unified laser-induced fluorescence technique for conducting planar measurements of temperature, pressure and velocity in nonreacting, highly compressible flows has been developed, validated and demonstrated. Planar fluorescence from iodine, seeded into air, was induced by an argon-ion laser and collected using a liquid-nitrogen cooled CCD camera. In the measurement technique, temperature is determined from the fluorescence induced with the laser operated broad band. Pressure and velocity are determined from the shape and position of the fluorescence excitation spectrum which is measured with the laser operated narrow band. The measurement approach described herein provides a means of obtaining accurate, spatially-complete maps of the primary flow field parameters in a wide variety of cold supersonic and transonic flows.

  2. [Trace elements storage peculiarities and metallothionein content in human thyroid gland under iodine deficiency euthyroid nodular goiter].

    PubMed

    Fal'fushins'ka, H I; Hnatyshyna, L L; Osadchuk, O Ĭ; Shydlovs'kyĭ, V O; Stoliar, O B

    2014-01-01

    Accumulation of iodine and copper in the node, paranodular and contralateral (not affected tissue by node) tissues of thyroid gland in relation to the level of metal-binding proteins, potential antioxidants and oxidative changes in tissue was investigated. To assess the severity of the pathological process the molecular markers of cytotoxicity were used. The reduction of total iodine (by 19.5%), increase of inorganic iodine fraction (by 82.4%) and total copper content (twice) in paranodular and nodular tissues compared with contrlateral part have been established. Excess of copper in goitrous-changes tissue was partially accumulated in the metallothioneins. The level of metal-binding form of metallothioneins and reserve of free thiols of these proteins was higher two-three times and lower content of reduced glutathione in node-affected tissue compared to the contralateral part. Signs of cytotoxicity among them: higher cathepsine D free activity (up to 84.6% and 134.4% in paranodular tissue and node respectively) and higher level of DNA strand breaks in the node (up to 22.6%) were observed. In paranodular tissue the range of indices variability compared with parenchyma of contralateral part is shorter than in the node. Thus, under low level of iodine organification and high copper level in goitrous-modified tissue of thyroid gland metallothionein may provide a partial compensatory effect on prooxidative processes.

  3. Iodine Affects Differentiation and Migration Process in Trophoblastic Cells.

    PubMed

    Olivo-Vidal, Zendy Evelyn; Rodríguez, Roció Coutiño; Arroyo-Helguera, Omar

    2016-02-01

    Iodine deficiency is associated with oxidative stress increase and preeclampsia during gestation, suggesting that iodine concentration plays an important role in the normal placenta physiology. The question raised is to analyze the effect of iodine deficiency on oxidative stress, viability, differentiation, and migration process and changes in the expression of differentiation and migration markers. Iodine deprivation was done using potassium perchlorate (KCLO4) to block sodium iodide symporter (NIS) transporter and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid DIDS to inhibit pendrine (PEN) transport for 3-48 h. Then trophoblast cells were treated with low iodine doses of 5-500 μM and high iodine doses of 100-5000 μM. Oxidative stress, viability, and human chorionic gonadotropin (hGC) were measured by colorimetric methods. Migration throphoblast cells were evaluated by both wound healing and Boyden chamber assays. Changes in mRNA expression were analyzed by real-time RT-PCR. Iodine deprivation induces a significant increase of reactive oxygen species (ROS), viability, and migration process vs control cells. We found a significant overregulation in the mRNA's peroxisome proliferator-activated receptor (PPAR-gamma), Snail, and matrix metalloproteinase-9 (MMP-9) mRNA's in cells deprived of iodine, as well as a down glial cell missing-1 (GCM-1) regulation, hGC, pregnancy-associated plasma protein-A (PAPP-A), and E-cadherin mRNA expression. The expression of hypoxic induction factor alpha (HIFα) mRNA does not change with iodine deprivation. In cells deprived of iodine, supplementing low iodine doses (5-500 μM) does not induce any significant changes in viability. However, ROS and migration process were decreased, although we found an increased human chorionic gonadotropin (hCG) secretion as a differentiation marker. In addition, we found that PPAR-gamma, Snail, and MPP-9 mRNAs expression are downregulated with low iodine doses, in contrast with GCM-1, PAPP

  4. Influence of texture on iodine-induced stress corrosion cracking of Zircaloy-4 cladding tubes

    NASA Astrophysics Data System (ADS)

    Schuster, I.; Lemaignan, C.

    1992-07-01

    A specific study was carried out to measure the influence of texture on the behaviour of Zircaloy-4 under iodine-induced stress corrosion cracking. The aim was to determine the relative effects of various metallurgical parameters involved in fuel rod fracture by pellet-clad interaction (PCI). Cladding tubes of different geometries were manufactured from a given Zircaloy-4 ingot. In this way tubes with different textures were obtained. Rings from these tubes were then subjected to slow tensile tests in an inert atmosphere and in an iodine vapour atmosphere. The sensitivity of the tubes to stress corrosion cracking is quantified by the loss of ductility on fracture between the tests in each atmosphere. Combined with the findings of other studies, the results showed that: (a) texture has a strong effect on the stress corrosion cracking behaviour of Zircaloy-4, (b) the mechanical properties do not have any bearing on the material behaviour under stress corrosion cracking, and that the better behaviour of a recrystallized material — compared to the same material in a stress-relieved state — can be explained solely by the texture effect, (c) texture is a more important parameter than chemical composition of Zircaloy-4, on condition that this composition remains within the ASTM specification. The conflict between the various mechanisms involved in stress corrosion crack propagation may explain these observations. Preliminary extrapolation of these conclusions to the irradiated material shows that a more specific study is needed using appropriate parameters.

  5. Threonine-deficient diets induced changes in hepatic bioenergetics

    PubMed Central

    Ross-Inta, Catherine M.; Zhang, Yi-Fan; Almendares, Andrew; Giulivi, Cecilia

    2009-01-01

    Diets deficient in an indispensable amino acid are known to suppress food intake in rats. Few studies were focused at understanding how amino acid-deficient diets may elicit biochemical changes at the mitochondrial level. The goal of this study was to evaluate mitochondrial function in rats fed diets with 0.00, 0.18, 0.36, and 0.88% threonine (Thr) (set at 0, 30, 60, and 140% of Thr requirement for growth). Here, it is described for the first time that Thr-deficient diets induce a specific uncoupling of mitochondria in liver, especially with NADH-linked substrates, not observed in heart (except for Thr-devoid diet). The advantage of this situation would be to provide ATP to support growth and maintenance when high-quality protein food (or wealth of high-quality food in general) is available, whereas Thr-deficient diets (or deficient-quality protein food) promote the opposite, increasing mitochondrial uncoupling in liver. The uncoupling with NADH substrates would favor the use of nutrients as energy sources with higher FADH-to-NADH ratios, such as fat, minimizing the first irreversible NADH-dependent catabolism of many amino acids, including Thr, thus enhancing the use of the limiting amino acid for protein synthesis when a low quality protein source is available. PMID:19228885

  6. Experimental investigation of a supersonic swept ramp injector using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Hartfield, Roy J.; Hollo, Steven D.; Mcdaniel, James C.

    1990-01-01

    Planar measurements of injectant mole fraction and temperature have been conducted in a nonreacting supersonic combustor configured with underexpanded injection in the base of a swept ramp. The temperature measurements were conducted with a Mach 2 test section inlet in streamwise planes perpendicular to the test section wall on which the ramp was mounted. Injection concentration measurements, conducted in cross flow planes with both Mach 2 and Mach 2.9 free stream conditions, dramatically illustrate the domination of the mixing process by streamwise vorticity generated by the ramp. These measurements, conducted using a nonintrusive optical technique (laser-induced iodine fluorescence), provide an accurate and extensive experimental data base for the validation of computation fluid dynamic codes for the calculation of highly three-dimensional supersonic combustor flow fields.

  7. Iodine supplementation in pregnancy - is it time?

    PubMed

    Taylor, P N; Vaidya, B

    2016-07-01

    Iodine is essential for the synthesis of thyroid hormone and optimal foetal neurological development. Pregnant women living in borderline or moderate-severe iodine deficient areas are at particularly high risk of being iodine deficient, and this may have important clinical consequences, particularly for the neurocognitive development of the offspring. It is a substantial problem and many countries including the United Kingdom are mild-moderately iodine deficient. Although the detrimental effects of severe iodine deficiency are well recognized, the benefits of correcting mild-to-moderate iodine deficiency are unclear due to a lack of randomized controlled trials in this area. However, observational data increasingly indicate that there may be substantial health and economic benefits from correcting iodine deficiency in pregnancy. There is now a growing trend from learned societies that iodine supplementation should be utilized in pregnancy in countries with mild-to-moderate iodine deficiency. The dose of iodine supplement needs to reflect local iodine status and iodization policies and will need careful monitoring at the population level to ensure doses to prevent under/excess dosing which would undermine the potential benefits. National tailored guidance is therefore essential. PMID:26998765

  8. Assessment of DNA double-strand breaks induced by intravascular iodinated contrast media following in vitro irradiation and in vivo, during paediatric cardiac catheterization.

    PubMed

    Gould, Richard; McFadden, Sonyia L; Horn, Simon; Prise, Kevin M; Doyle, Philip; Hughes, Ciara M

    2016-01-01

    Paediatric cardiac catheterizations may result in the administration of substantial amounts of iodinated contrast media and ionizing radiation. The aim of this work was to investigate the effect of iodinated contrast media in combination with in vitro and in vivo X-ray radiation on lymphocyte DNA. Six concentrations of iodine (15, 17.5, 30, 35, 45, and 52.5 mg of iodine per mL blood) represented volumes of iodinated contrast media used in the clinical setting. Blood obtained from healthy volunteers was mixed with iodinated contrast media and exposed to radiation doses commonly used in paediatric cardiac catheterizations (0 mGy, 70 mGy, 140 mGy, 250 mGy and 450 mGy). Control samples contained no iodine. For in vivo experimentation, pre and post blood samples were collected from children undergoing cardiac catheterization, receiving iodine concentrations of up to 51 mg of iodine per mL blood and radiation doses of up to 400 mGy. Fluorescence microscopy was performed to assess γH2AX-foci induction, which corresponded to the number of DNA double-strand breaks. The presence of iodine in vitro resulted in significant increases of DNA double-strand breaks beyond that induced by radiation for ≥ 17.5 mg/mL iodine to blood. The in vivo effects of contrast media on children undergoing cardiac catheterization resulted in a 19% increase in DNA double-strand breaks in children receiving an average concentration of 19 mg/mL iodine to blood. A larger investigation is required to provide further information of the potential benefit of lowering the amount of iodinated contrast media received during X-ray radiation investigations.

  9. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    SciTech Connect

    Lefevre, Sophie; Sliwa, Dominika; Rustin, Pierre; Camadro, Jean-Michel; Santos, Renata

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  10. Inhibition of autophagy stimulate molecular iodine-induced apoptosis in hormone independent breast tumors

    SciTech Connect

    Singh, Preeti; Godbole, Madan; Rao, Geeta; Annarao, Sanjay; Mitra, Kalyan; Roy, Raja; Ingle, Arvind; Agarwal, Gaurav; Tiwari, Swasti

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Molecular iodine (I{sub 2}) causes non-apoptotic cell death in MDA-MB231 breast tumor cells. Black-Right-Pointing-Pointer Autophagy is activated as a survival mechanism in response to I{sub 2} in MDA-MB231. Black-Right-Pointing-Pointer Autophagy inhibition sensitizes tumor cells to I{sub 2}-induced apoptotic cell death. Black-Right-Pointing-Pointer Autophagy inhibitor potentiates apoptosis and tumor regressive effects of I{sub 2} in mice. -- Abstract: Estrogen receptor negative (ER{sup -ve}) and p53 mutant breast tumors are highly aggressive and have fewer treatment options. Previously, we showed that molecular Iodine (I{sub 2}) induces apoptosis in hormone responsive MCF-7 breast cancer cells, and non-apoptotic cell death in ER{sup -ve}-p53 mutant MDA-MB231 cells (Shrivastava, 2006). Here we show that I{sub 2} (3 {mu}M) treatment enhanced the features of autophagy in MDA-MB231 cells. Since autophagy is a cell survival response to most anti-cancer therapies, we used both in vitro and in vivo systems to determine whether ER{sup -ve} mammary tumors could be sensitized to I{sub 2}-induced apoptosis by inhibiting autophagy. Autophagy inhibition with chloroquine (CQ) and inhibitors for PI3K (3MA, LY294002) and H+/ATPase (baflomycin) resulted in enhanced cell death in I{sub 2} treated MDA-MB231 cells. Further, CQ (20 {mu}M) in combination with I{sub 2}, showed apoptotic features such as increased sub-G1 fraction ({approx}5-fold), expression of cleaved caspase-9 and -3 compared to I{sub 2} treatment alone. Flowcytometry of I{sub 2} and CQ co-treated cells revealed increase in mitochondrial membrane permeability (p < 0.01) and translocation of cathepsin D activity to cytosol relative to I{sub 2} treatment. For in vivo studies ICRC mice were transplanted subcutaneously with MMTV-induced mammary tumors. A significant reduction in tumor volumes, as measured by MRI, was found in I{sub 2} and CQ co-treated mice relative to I{sub 2} or

  11. Leptin Deficiency Causes Insulin Resistance Induced by Uncontrolled Diabetes

    PubMed Central

    German, Jonathan P.; Wisse, Brent E.; Thaler, Joshua P.; Oh-I, Shinsuke; Sarruf, David A.; Ogimoto, Kayoko; Kaiyala, Karl J.; Fischer, Jonathan D.; Matsen, Miles E.; Taborsky, Gerald J.; Schwartz, Michael W.; Morton, Gregory J.

    2010-01-01

    OBJECTIVE Depletion of body fat stores during uncontrolled, insulin-deficient diabetes (uDM) results in markedly reduced plasma leptin levels. This study investigated the role of leptin deficiency in the genesis of severe insulin resistance and related metabolic and neuroendocrine derangements induced by uDM. RESEARCH DESIGN AND METHODS Adult male Wistar rats remained nondiabetic or were injected with the β-cell toxin, streptozotocin (STZ) to induce uDM and subsequently underwent subcutaneous implantation of an osmotic minipump containing either vehicle or leptin at a dose (150 μg/kg/day) designed to replace leptin at nondiabetic plasma levels. To control for leptin effects on food intake, another group of STZ-injected animals were pair fed to the intake of those receiving leptin. Food intake, body weight, and blood glucose levels were measured daily, with body composition and indirect calorimetry performed on day 11, and an insulin tolerance test to measure insulin sensitivity performed on day 16. Plasma hormone and substrate levels, hepatic gluconeogenic gene expression, and measures of tissue insulin signal transduction were also measured. RESULTS Physiologic leptin replacement prevented insulin resistance in uDM via a mechanism unrelated to changes in food intake or body weight. This effect was associated with reduced total body fat and hepatic triglyceride content, preservation of lean mass, and improved insulin signal transduction via the insulin receptor substrate–phosphatidylinositol-3-hydroxy kinase pathway in the liver, but not in skeletal muscle or adipose tissue. Although physiologic leptin replacement lowered blood glucose levels only slightly, it fully normalized elevated plasma glucagon and corticosterone levels and reversed the increased hepatic expression of gluconeogenic enzymes characteristic of rats with uDM. CONCLUSIONS We conclude that leptin deficiency plays a key role in the pathogenesis of severe insulin resistance and related endocrine

  12. Flowfield measurements in a model scramjet combustion using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Mcdaniel, J. C., Jr.

    1984-01-01

    Preliminary designs were completed for an iodine mixing chamber and the optical setup to be used with a modified wind tunnel in obtaining accurate, spatially resolved measurements of variables in the flowfield of a model nonreacting scramjet combustor. Schematics of the iodine-seeded wind tunnel and a sketch of the charcoal filter for removing the iodine are included along with a cutaway section of the laboratory.

  13. Serotonin deficiency exacerbates acetaminophen-induced liver toxicity in mice.

    PubMed

    Zhang, Jingyao; Song, Sidong; Pang, Qing; Zhang, Ruiyao; Zhou, Lei; Liu, Sushun; Meng, Fandi; Wu, Qifei; Liu, Chang

    2015-01-29

    Acetaminophen (APAP) overdose is a major cause of acute liver failure. Peripheral 5-hydroxytryptamine (serotonin, 5-HT) is a cytoprotective neurotransmitter which is also involved in the hepatic physiological and pathological process. This study seeks to investigate the mechanisms involved in APAP-induced hepatotoxicity, as well as the role of 5-HT in the liver's response to APAP toxicity. We induced APAP hepatotoxicity in mice either sufficient of serotonin (wild-type mice and TPH1-/- plus 5- Hydroxytryptophan (5-HTP)) or lacking peripheral serotonin (Tph1-/- and wild-type mice plus p-chlorophenylalanine (PCPA)). Mice with sufficient 5-HT exposed to acetaminophen have a significantly lower mortality rate and a better outcome compared with mice deficient of 5-HT. This difference is at least partially attributable to a decreased level of inflammation, oxidative stress and endoplasmic reticulum (ER) stress, Glutathione (GSH) depletion, peroxynitrite formation, hepatocyte apoptosis, elevated hepatocyte proliferation, activation of 5-HT2B receptor, less activated c-Jun NH₂-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1α in the mice sufficient of 5-HT versus mice deficient of 5-HT. We thus propose a physiological function of serotonin that serotonin could ameliorate APAP-induced liver injury mainly through inhibiting hepatocyte apoptosis ER stress and promoting liver regeneration.

  14. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    PubMed Central

    Hohmann, Miriam S. N.; Cardoso, Renato D. R.; Pinho-Ribeiro, Felipe A.; Crespigio, Jefferson; Cunha, Thiago M.; Alves-Filho, José C.; da Silva, Rosiane V.; Pinge-Filho, Phileno; Ferreira, Sergio H.; Cunha, Fernando Q.; Casagrande, Rubia; Verri, Waldiceu A.

    2013-01-01

    5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO−/−) mice and background wild type mice were challenged with APAP (0.3–6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO−/− mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO−/− mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage. PMID:24288682

  15. A mechanism for biologically-induced iodine emissions from sea-ice

    NASA Astrophysics Data System (ADS)

    Boxe, C.

    2015-12-01

    Ground- and satellite-based measurements reported high concentrations of iodine monoxide (IO) in coastal Antarctica. The sources of such a large iodine burden in the coastal Antarctic atmosphere remain unknown. We propose a mechanism for iodine release from sea-ice based on the premise that micro-algae are the primary source of iodine emissions in this environment. The emissions are triggered by the biological production of iodide (I-) and hypoiodous acid (HOI) from micro-algae (contained within and underneath sea-ice) and their diffusion through sea-ice brine channels, to accumulate in a thin brine layer (BL) on the surface of sea-ice. Prior to reaching the BL, the diffusion timescale of iodine within sea-ice is depth-dependent. The BL is also a vital component of the proposed mechanism as it enhances the chemical kinetics of iodine-related reactions, which allows for the efficient release of iodine to the polar boundary layer. We suggest iodine is released to the atmosphere via 3 possible pathways: (1) emitted from the BL and then transported throughout snow atop sea-ice, to be released to the atmosphere; (2) released directly from the BL to the atmosphere in regions of sea-ice that are not covered with snowpack; or (3) emitted to the atmosphere directly through fractures in the sea-ice pack. To investigate the proposed biology-ice-atmosphere coupling at coastal Antarctica we use a multiphase model that incorporates the transport of iodine species, via diffusion, at variable depths, within brine channels of sea-ice. Model simulations were conducted to interpret observations of elevated springtime IO in the coastal Antarctic, around the Weddell Sea. While a lack of experimental and observational data adds uncertainty to the model predictions, nevertheless the results show that the levels of inorganic iodine (i.e., I2, IBr, ICl) released from sea-ice through this mechanism could account for the observed IO concentrations during this timeframe. The model results

  16. A mechanism for biologically-induced iodine emissions from sea-ice

    NASA Astrophysics Data System (ADS)

    Saiz-Lopez, A.; Blaszczak-Boxe, C. S.; Carpenter, L. J.

    2015-04-01

    Ground- and satellite-based measurements have reported high concentrations of iodine monoxide (IO) in coastal Antarctica. The sources of such a large iodine burden in the coastal Antarctic atmosphere remain unknown. We propose a mechanism for iodine release from sea-ice based on the premise that micro-algae are the primary source of iodine emissions in this environment. The emissions are triggered by the biological production of iodide (I-) and hypoiodous acid (HOI) from micro-algae (contained within and underneath sea-ice) and their diffusion through sea-ice brine channels, to accumulate in the quasi-liquid layer (QLL) on the surface of sea-ice. Prior to reaching the QLL, the diffusion timescale of iodine within sea-ice is depth-dependent. The QLL is also a vital component of the proposed mechanism as it enhances the chemical kinetics of iodine-related reactions, which allows for the efficient release of iodine to the polar boundary layer. We suggest iodine is released to the atmosphere via 3 possible pathways: (1) emitted from the QLL and then transported throughout snow atop sea-ice, to be released to the atmosphere, (2) released directly from the QLL to the atmosphere in regions of sea-ice that are not covered with snowpack; or (3) emitted to the atmosphere directly through fractures in the sea-ice pack. To investigate the proposed biology-ice-atmosphere coupling at coastal Antarctica we use a multiphase model that incorporates the transport of iodine species, via diffusion, at variable depths, within brine channels of sea-ice. Model simulations were conducted to interpret observations of elevated springtime IO in the coastal Antarctic, around the Weddell Sea. The results show that the levels of inorganic iodine (i.e., I2, IBr, ICl) released from sea-ice through this mechanism could account for the observed IO concentrations during this timeframe. The model results also indicate that iodine may trigger the catalytic release of bromine from sea-ice through phase

  17. Single-shot volumetric laser induced fluorescence (VLIF) measurements in turbulent flows seeded with iodine.

    PubMed

    Wu, Yue; Xu, Wenjiang; Lei, Qingchun; Ma, Lin

    2015-12-28

    This work reports the experimental demonstration of single-shot visualization of turbulent flows in all three spatial dimensions (3D) based on volumetric laser induced fluorescence (VLIF). The measurements were performed based on the LIF signal of iodine (I2) vapor seeded in the flow. In contrast to established planar LIF (PLIF) technique, the VLIF technique excited the seeded I2 vapor volumetrically by a thick laser slab. The volumetric LIF signals emitted were then simultaneously collected by a total of five cameras from five different orientations, based on which a 3D tomographic reconstruction was performed to obtain the 3D distribution of the I2 vapor in the target flow. Single-shot measurements (with a measurement duration of a few ns) were demonstrated in a 50 mm × 50 mm × 50 mm volume with a nominal spatial resolution of 0.42 mm and an actual resolution of ~0.71 mm in all three dimensions (corresponding to a total of 120 × 120 × 120 voxels). PMID:26832005

  18. Subwavenumber charge-coupled device spectrometer calibration using molecular iodine laser-induced fluorescence

    SciTech Connect

    Lambert, Joseph G.; Hernandez-Diaz, Carlos; Williamson, J. Charles

    2010-01-15

    Spectrometers configured with charge-coupled devices (CCD) or other array-based detectors require calibration to convert from the pixel coordinate to a spectral coordinate. A CCD calibration method well suited for Raman spectroscopy has been developed based on the 514.5 nm Ar{sup +} laser-induced fluorescence (LIF) spectrum of room-temperature molecular iodine vapor. Over 360 primary and secondary I{sub 2} LIF calibration lines spanning 510-645 nm were identified as calibrant peaks using an instrumental resolution of 1 cm{sup -1}. Two instrument calibration functions were evaluated with these peaks: a second-order polynomial and a function derived from simple optomechanical considerations. The latter function provided better fitting characteristics. Calibration using I{sub 2} LIF was tested with measurements of both laser light scattering and Raman spectra. The I{sub 2} LIF reference spectra and the signal spectra were recorded simultaneously, with no cross talk, by separating the two signals spatially along the vertical axis of the CCD imager. In this way, every CCD image could be independently calibrated. An accuracy and a precision of {+-}0.05 cm{sup -1} were achieved with this calibration technique.

  19. Thyroid and iodine nutritional status: a UK perspective.

    PubMed

    Vanderpump, Mark

    2014-12-01

    Iodine is an essential component of the thyroid hormones, which play a crucial role in brain and neurological development. At least one-third of the world's population is estimated to be iodine deficient predominantly in developing countries. Recently concern had also been expressed about the iodine status in industrialised countries such as the UK. A recent survey of the UK iodine status found that that more than two-thirds of schoolgirls aged 14-15 years were iodine deficient due to the reduced milk intake. Maternal iodine deficiency in pregnancy is correlated with cognitive outcomes such as intelligence quotient and reading ability in offspring. No randomised trial data exist for iodine supplementation in mild-moderate iodine-deficient pregnant women. It is possible to combine population interventions to reduce population salt intake with salt iodisation programmes in order to maintain adequate levels of iodine nutrition.

  20. In the eye of the storm: iodinated contrast medium induced thyroid storm presenting as cardiopulmonary arrest.

    PubMed

    Alkhuja, Samer; Pyram, Ronald; Odeyemi, Olutunde

    2013-01-01

    The administration of iodinated contrast medium may lead to excess free thyroid hormone release and cause thyroid storm. A woman presented to the emergency department with dyspnea, hemoptysis, and intermittent bilateral lower extremities edema. Physical examination revealed mildly enlarged thyroid. Patient underwent a computed tomography scan of the chest with intravenous iodinated contrast medium to rule out pulmonary embolism, the patient developed a thyroid storm second to iodinated contrast medium injection. Proper treatment was provided and the patient had a good outcome. We present this case of an unusual presentation of a thyroid storm with cardiac arrest. This case illustrates that evaluating thyroid function tests in patients with an enlarged thyroid prior to the administration of iodinated contrast medium could prevent the development of thyroid storm.

  1. Epidemiological trends of iodine-related thyroid disorders: an example from Slovenia.

    PubMed

    Gaberšček, Simona; Zaletel, Katja

    2016-06-01

    The epidemiology of thyroid disorders is significantly associated with iodine supply. In 1999, Slovenia increased iodine content in kitchen salt from 10 mg to 25 mg of potassium iodide per kg of salt. According to the WHO criteria, Slovenia shifted from a mildly iodine-deficient country to a country with adequate iodine intake. Ten years after the increase in iodine intake, the incidence of diffuse goitre and thyroid autonomy decreased. Now patients with diffuse goitre and thyroid autonomy reach older age than the patients before the increase in iodine intake. In addition, patients with thyroid autonomy are less frequently hyperthyroid than ten years ago and iodine-induced hyperthyroidism is less severe. The incidence of highly malignant thyroid carcinoma has also dropped. However, the incidence of Hashimoto's thyroiditis increased, most probably in genetically predisposed individuals. Over the last ten years, many animal and in vitro studies evaluated the effects of endocrine disrupting chemicals (EDC) on various aspects of the thyroid function. They mostly studied the effects of polychlorinated biphenyls (PCBs) and dioxins, brominated flame retardants, phthalates, bisphenol A, perfluorinated chemicals, and perchlorate. However, human studies on the effects of EDCs on the thyroid function are very scarce, especially the long-term ones. What they do suggest is that PCBs and dioxins interfere with the transport of thyroid hormones and adversely affect the thyroid function. Many authors agree that iodine deficiency predisposes the thyroid gland to harmful effects of EDCs. Therefore the effects of EDCs in iodine-deficient areas could be more severe than in areas with adequate iodine intake. PMID:27331296

  2. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    SciTech Connect

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou; Peng, Shuangqing; Wang, Weidong; Li, Rong

    2015-09-15

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  3. Twenty-four hour radioactive iodine uptake in 35 patients with amiodarone associated thyrotoxicosis

    SciTech Connect

    Martino, E.; Aghini-Lombardi, F.; Lippi, F.; Baschieri, L.; Safran, M.; Braverman, L.E.; Pinchera, A.

    1985-12-01

    Amiodarone associated thyrotoxicosis (AAT) occurs in approximately 10% of patients treated with this iodine rich drug in areas of mild iodine deficiency. The thyroid radioactive iodine uptake (RAIU) is usually undetectable or very low in iodine-induced thyrotoxicosis. In the present study, 35 patients with AAT were evaluated. Twelve patients had no thyroid abnormalities by physical exam and all had 24-hr RAIU less than or equal to 4%. In contrast, nine of 11 patients with AAT and diffuse goiters and eight of 12 patients with AAT and nodular goiters had RAIU values greater than 8%. In patients with AAT and goiter it appears possible that the thyroid fails to adapt normally to the excess iodide load, resulting in an inappropriately high RAIU in the presence of excess plasma iodine.

  4. Iodine Concentration in Breastmilk and Urine among Lactating Women of Bhaktapur, Nepal

    PubMed Central

    Henjum, Sigrun; Kjellevold, Marian; Ulak, Manjeswori; Chandyo, Ram K.; Shrestha, Prakash S.; Frøyland, Livar; Strydom, Emmerentia E.; Dhansay, Muhammad A.; Strand, Tor A.

    2016-01-01

    Adequate iodine concentration in breastmilk (BMIC) is essential for optimal neonatal thyroid hormone synthesis and neurological development in breastfed infants. For many decades, iodine deficiency has been a public health problem in Nepal. However, recently, excessive iodine intakes among Nepali infants have been reported. This study aimed to measure BMIC and urinary iodine concentration (UIC) among lactating women in a peri-urban area of Nepal. Iodine concentration was measured in spot urine (n = 485) and breastmilk samples (n = 291) of 500 randomly selected lactating women. The median (p25, p75) BMIC and median UIC were 250 (130, 370) µg/L and 230 (135–377) µg/L, respectively. Around 82% had BMIC > 100 µg/L, 61% had BMIC > 200 µg/L and 81% had UIC > 100 µg/L, 37% had >300 µg/L and 20% had >500 µg/L. In multiple linear regression models, time since birth (β 3.0, 95% CI (0.2, 5.0)) and UIC (β 1.0, 95% CI (0.1, 2.0)) were associated with BMIC, explaining 26% of the variance. A large proportion of the women had adequate BMIC and UIC; however, a subset had high iodine concentrations. These findings emphasize the importance of carefully monitoring iodine intake to minimize the risk of iodine excess and subsequently preventing transient iodine-induced hypothyroidism in breastfed infants. PMID:27136582

  5. Current challenges in meeting global iodine requirements.

    PubMed

    Eastman, Creswell J; Jooste, Pieter

    2012-01-01

    Iodine deficiency is a global problem of immense magnitude afflicting 2 billion of the world's population. The adverse effects of iodine deficiency in humans, collectively termed iodine deficiency disorders, result from decreased thyroid hormone production and action, and vary in severity from thyroid enlargement (goiter) to severe, irreversible brain damage, termed endemic cretinism. Thyroid hormone is essential throughout life, but it is critical for normal brain development in the fetus and throughout childhood. During pregnancy, maternal thyroid hormone production must increase by 25-50% to meet maternal-fetal requirements. The principal sources of iodine in the diet include milk and dairy products, seafoods and foods with added iodized salt. Vegetables, fruits and cereals are generally poor sources of iodine because most of our soils and water supplies are deficient in iodine. The accepted solution to the problem is Universal Salt Iodization where all salt for human and animal consumption is iodized at a level of 20-40 µg/g. In principle, mandatory fortification represents the most effective public health strategy where safety and efficacy can be assured and there is a demonstrated need for the nutrient in the population. Voluntary fortification of salt and other foods has many limitations and few benefits. Iodine supplementation is a useful, but expensive, inefficient and unsustainable strategy for preventing iodine deficiency. The current worldwide push to decrease salt intake to prevent cardiovascular disease presents an entirely new challenge in addressing iodine deficiency in both developing and developed countries. PMID:25825304

  6. Iodine poisoning

    MedlinePlus

    Iodine is found in: Amiodarone (Cordarone) Chemicals (catalysts) for photography and engraving Dyes and inks Lugol's solution Pima syrup Potassium iodide Radioactive iodine used for certain medical tests or the treatment ...

  7. New Compounds Induce Brassinosteroid Deficient-like Phenotypes in Rice.

    PubMed

    Matsumoto, Tadashi; Yamada, Kazuhiro; Iwasaki, Ikuko; Yoshizawa, Yuko; Oh, Keimei

    2013-01-01

    Brassinosteroids (BRs) are steroidal plant hormones with potent plant growth promoting activity. Because BR-deficient mutants of rice exhibit altered plant architecture and important agronomic traits, we conducted a systemic search for specific inhibitors of BR biosynthesis to manipulate the BR levels in plant tissues. Although previous studies have been conducted with BR biosynthesis inhibitors in dicots, little is known regarding the effects of BR biosynthesis inhibition in monocot plants. In this work, we used potent inhibitors of BR biosynthesis in Arabidopsis, and we performed a hydroponic culture of rice seedlings to evaluate the effects of BR biosynthesis inhibition. Among the test compounds, we found that 1-[[2-(4-Chlorophenyl)-4-(phenoxymethyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (1) is a potent inhibitor that could induce phenotypes in rice seedlings that were similar to those observed in brassinosteroid deficient plants. The IC50 value for the retardation of plant growth in rice seedlings was approximately 1.27 ± 0.43 μM. The IC50 value for reducing the bending angle of the lamina joint was approximately 0.55 ± 0.15 μM. PMID:27137391

  8. Influence of the gaseous mixture composition on accuracy of molecular iodine on-line detection by laser-induced fluorescence method

    NASA Astrophysics Data System (ADS)

    Kireev, S. V.; Shnyrev, S. L.

    2016-07-01

    This paper informs on research into the influence of the composition of gaseous mixtures analyzed on the accuracy of on-line molecular iodine detection by laser-induced fluorescence in various gaseous media—in atmospheric air and in technological mixtures formed during reprocessing of spent nuclear fuel. The paper shows that by considering the composition of buffer media and parts of its components, the accuracy of iodine content measurement may be increased in several times.

  9. Antineoplastic effect of iodine and iodide in dimethylbenz[a]anthracene-induced mammary tumors: association between lactoperoxidase and estrogen-adduct production.

    PubMed

    Soriano, Ofelia; Delgado, Guadalupe; Anguiano, Brenda; Petrosyan, Pavel; Molina-Servín, Edith D; Gonsebatt, Maria E; Aceves, Carmen

    2011-08-01

    Several groups, including ours, have reported that iodine exhibited antiproliferative and apoptotic effects in various cancer cells only if this element is supplemented as molecular iodine, or as iodide, to cells that are able to oxidize it with the enzyme thyroperoxidase. In this study, we analyzed the effect of various concentrations of iodine and/or iodide in the dimethylbenz[a]anthracene (DMBA) mammary cancer model in rats. The results show that 0.1% iodine or iodide increases the expression of peroxisome proliferator-activated receptor type γ (PPARγ), triggering caspase-mediated apoptosis pathways in damaged mammary tissue (DMBA-treated mammary gland) as well as in frank mammary tumors, but not in normal mammary gland. DMBA treatment induces the expression of lactoperoxidase, which participates in the antineoplastic effect of iodide and could be involved in the pro-neoplastic effect of estrogens, increasing the formation of DNA adducts. In conclusion, our results show that a supplement of 0.1% molecular iodine/potassium iodide (0.05/0.05%) exert antineoplastic effects, preventing estrogen-induced DNA adducts and inducing apoptosis through PPARγ/caspases in pre-cancer and cancerous cells. Since this iodine concentration does not modify the cytology (histology, apoptosis rate) or physiology (triiodothyronine and thyrotropin) of the thyroid gland, we propose that it be considered as an adjuvant treatment for premenopausal mammary cancer.

  10. Caspase-2 deficiency accelerates chemically induced liver cancer in mice.

    PubMed

    Shalini, S; Nikolic, A; Wilson, C H; Puccini, J; Sladojevic, N; Finnie, J; Dorstyn, L; Kumar, S

    2016-10-01

    Aberrant cell death/survival has a critical role in the development of hepatocellular carcinoma (HCC). Caspase-2, a cell death protease, limits oxidative stress and chromosomal instability. To study its role in reactive oxygen species (ROS) and DNA damage-induced liver cancer, we assessed diethylnitrosamine (DEN)-mediated tumour development in caspase-2-deficient (Casp2(-/-)) mice. Following DEN injection in young animals, tumour development was monitored for 10 months. We found that DEN-treated Casp2(-/-) mice have dramatically elevated tumour burden and accelerated tumour progression with increased incidence of HCC, accompanied by higher oxidative damage and inflammation. Furthermore, following acute DEN injection, liver injury, DNA damage, inflammatory cytokine release and hepatocyte proliferation were enhanced in mice lacking caspase-2. Our study demonstrates for the first time that caspase-2 limits the progression of tumourigenesis induced by an ROS producing and DNA damaging reagent. Our findings suggest that after initial DEN-induced DNA damage, caspase-2 may remove aberrant cells to limit liver damage and disease progression. We propose that Casp2(-/-) mice, which are more susceptible to genomic instability, are limited in their ability to respond to DNA damage and thus carry more damaged cells resulting in accelerated tumourigenesis.

  11. Iodine determination in food by inductively coupled plasma mass spectrometry after digestion by microwave-induced combustion.

    PubMed

    Mesko, Márcia F; Mello, Paola A; Bizzi, Cezar A; Dressler, Valderi L; Knapp, Guenter; Flores, Erico M M

    2010-09-01

    Iodine determination in food samples was performed by inductively coupled plasma mass spectrometry (ICP-MS) after digestion by microwave-induced combustion (MIC). Sample masses up to 500 mg of bovine liver, corn starch, milk powder, or wheat flour were completely combusted using the MIC system. Ammonium nitrate (6 mol l(-1) solution, 50 μl) was used as an aid for ignition and vessels were charged with 15 bar of O(2). The use of H(2)O, 0.9 mmol l(-1) H(2)O(2), 10 to 50 mmol l(-1) (NH(4))(2)CO(3) and 56 mmol l(-1) tetramethylammonium hydroxide was investigated as absorbing solutions, as well as the suitability of performing a reflux step after the combustion process. Digestion of food samples by pressurized microwave-assisted acid digestion, microwave-assisted extraction and conventional extraction of iodine in alkaline solution were also evaluated. Iodine recoveries higher than 99% were obtained using MIC and 50 mmol l(-1) (NH(4))(2)CO(3) or 56 mmol l(-1) tetramethylammonium hydroxide as absorbing solution and with 5 min for the reflux step. Accuracy was evaluated using certified reference materials (bovine muscle, corn bran, and milk powder) and agreement better than 97% was obtained. The limit of quantification by MIC and further ICP-MS determination was 0.002 µg g(-1). Blanks were always low and no memory effects were observed. Digestion by MIC allowed the processing of up to eight samples by each run in 25 min with high efficiency of digestion (residual carbon content lower than 1%) providing a suitable medium for further iodine determination by ICP-MS. PMID:20464381

  12. Iodine determination in food by inductively coupled plasma mass spectrometry after digestion by microwave-induced combustion.

    PubMed

    Mesko, Márcia F; Mello, Paola A; Bizzi, Cezar A; Dressler, Valderi L; Knapp, Guenter; Flores, Erico M M

    2010-09-01

    Iodine determination in food samples was performed by inductively coupled plasma mass spectrometry (ICP-MS) after digestion by microwave-induced combustion (MIC). Sample masses up to 500 mg of bovine liver, corn starch, milk powder, or wheat flour were completely combusted using the MIC system. Ammonium nitrate (6 mol l(-1) solution, 50 μl) was used as an aid for ignition and vessels were charged with 15 bar of O(2). The use of H(2)O, 0.9 mmol l(-1) H(2)O(2), 10 to 50 mmol l(-1) (NH(4))(2)CO(3) and 56 mmol l(-1) tetramethylammonium hydroxide was investigated as absorbing solutions, as well as the suitability of performing a reflux step after the combustion process. Digestion of food samples by pressurized microwave-assisted acid digestion, microwave-assisted extraction and conventional extraction of iodine in alkaline solution were also evaluated. Iodine recoveries higher than 99% were obtained using MIC and 50 mmol l(-1) (NH(4))(2)CO(3) or 56 mmol l(-1) tetramethylammonium hydroxide as absorbing solution and with 5 min for the reflux step. Accuracy was evaluated using certified reference materials (bovine muscle, corn bran, and milk powder) and agreement better than 97% was obtained. The limit of quantification by MIC and further ICP-MS determination was 0.002 µg g(-1). Blanks were always low and no memory effects were observed. Digestion by MIC allowed the processing of up to eight samples by each run in 25 min with high efficiency of digestion (residual carbon content lower than 1%) providing a suitable medium for further iodine determination by ICP-MS.

  13. National trends in iodine nutrition: is everyone getting enough?

    PubMed

    Pearce, Elizabeth N

    2007-09-01

    Iodine deficiency is an important public health problem worldwide. Until the 1920s, endemic iodine deficiency disorders were prevalent in the Great Lakes, Appalachian, and Northwestern regions of the United States. Iodized salt was responsible for eliminating endemic goiter in the United States and remains the mainstay of iodine deficiency disorder eradication efforts worldwide. Although urinary iodine values have decreased by 50% since the early 1970s, the United States remains iodine sufficient. However, U.S. iodine nutrition, particularly among women of childbearing age, may remain an area worthy of public health concern. There is a wide amount of variation in the iodine content of some common foods, and the iodine content of foods is not well reflected by package labeling. There needs to be increased awareness of the importance of adequate iodine nutrition, particularly during pregnancy and lactation, among the U.S. public.

  14. Iodothyronine deiodinase activities in fetal rat tissues at several levels of iodine deficiency: a role for the skin in 3,5,3'-triiodothyronine economy?

    PubMed

    Schröder-van der Elst, J P; van der Heide, D; Morreale de Escobar, G; Obregón, M J

    1998-05-01

    Iodothyronine deiodinases, types I, II, and III (D1, D2, and D3) activities were measured in tissues of fetal rats, at 18 and 21 days of gestation, at several levels of iodine deficiency (ID): mild ID diet (MID) and moderately severe ID, MID + 0.005% perchlorate (MID+P). D2 was present in fetal skin, increased between days 18 and 21, and also in MID and MID+P. In skin, D3 increased during ID at day 18, whereas there was a decrease at day 21. Skin T4 decreased in MID and MID+P, showing an inverse relationship with D2. Skin T3 decreased at day 18 in MID and MID+P but increased at day 21, probably because of the increased D2 and decreased D3, maintaining T3 concentrations. No effect of ID was observed on hepatic D1. D2 increased in brain and brown adipose tissue at day 21 in MID+P. No changes were found in maternal placental D2 and D3, but D2 and D3 increased in the fetal placenta at day 18 in MID+P. A higher level of D2 is present in fetal skin than in the brain. As the activity is increased, in even mild ID (and already at 18 days) it can be concluded that skin D2 is likely to be of considerable physiological importance, at least for fetal thyroid hormone economy, by contributing to the intracellular T3 content of the skin and, possibly, to the plasma T3.

  15. Planar measurement of flow field parameters in a nonreacting supersonic combustor using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Hartfield, Roy J., Jr.; Hollo, Steven D.; Mcdaniel, James C.

    1990-01-01

    A nonintrusive optical technique, laser-induced iodine fluorescence, has been used to obtain planar measurements of flow field parameters in the supersonic mixing flow field of a nonreacting supersonic combustor. The combustor design used in this work was configured with staged transverse sonic injection behind a rearward-facing step into a Mach 2.07 free stream. A set of spatially resolved measurements of temperature and injectant mole fraction has been generated. These measurements provide an extensive and accurate experimental data set required for the validation of computational fluid dynamic codes developed for the calculation of highly three-dimensional combustor flow fields.

  16. Prostaglandin E₂ is critical for the development of niacin-deficiency-induced photosensitivity via ROS production.

    PubMed

    Sugita, Kazunari; Ikenouchi-Sugita, Atsuko; Nakayama, Yasuko; Yoshioka, Haruna; Nomura, Takashi; Sakabe, Jun-Ichi; Nakahigashi, Kyoko; Kuroda, Etsushi; Uematsu, Satoshi; Nakamura, Jun; Akira, Shizuo; Nakamura, Motonobu; Narumiya, Shuh; Miyachi, Yoshiki; Tokura, Yoshiki; Kabashima, Kenji

    2013-01-01

    Pellagra is a photosensitivity syndrome characterized by three "D's": diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE2 production via induction of ROS formation. PMID:24131900

  17. Prostaglandin E₂ is critical for the development of niacin-deficiency-induced photosensitivity via ROS production.

    PubMed

    Sugita, Kazunari; Ikenouchi-Sugita, Atsuko; Nakayama, Yasuko; Yoshioka, Haruna; Nomura, Takashi; Sakabe, Jun-Ichi; Nakahigashi, Kyoko; Kuroda, Etsushi; Uematsu, Satoshi; Nakamura, Jun; Akira, Shizuo; Nakamura, Motonobu; Narumiya, Shuh; Miyachi, Yoshiki; Tokura, Yoshiki; Kabashima, Kenji

    2013-10-17

    Pellagra is a photosensitivity syndrome characterized by three "D's": diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE2 production via induction of ROS formation.

  18. Effects of increased iodine intake on thyroid disorders.

    PubMed

    Sun, Xin; Shan, Zhongyan; Teng, Weiping

    2014-09-01

    Iodine is a micronutrient essential for the production of thyroid hormones. Iodine deficiency is the most common cause of preventable mental impairment worldwide. Universal salt iodization (USI) has been introduced in many countries as a cost-effective and sustainable way to eliminate iodine deficiency disorders for more than 25 years. Currently, the relationship between USI and iodine excess has attracted more attention. Iodine excess can lead to hypothyroidism and autoimmune thyroiditis, especially for susceptible populations with recurring thyroid disease, the elderly, fetuses, and neonates. Nationwide USI was introduced in China in 1996. This review focused on the effects of iodine excess worldwide and particularly in China. PMID:25309781

  19. The importance of iodine in public health.

    PubMed

    Lazarus, John H

    2015-08-01

    Iodine (I) deficiency has been known for more than a century and is known to cause cretinism at the extreme end of the spectrum but also, importantly, impaired development and neurocognition in areas of mild deficiency. The WHO has indicated that median urinary iodine of 100-199 μg/l in a population is regarded as indicative of an adequate iodine intake. The understanding of the spectrum of iodine deficiency disorders led to the formation of The International Council for the Control of Iodine Deficiency Disorders which has promulgated the use of household iodized salt and the use of such salt in food processing and manufacture. Iodine deficiency is particularly important in pregnancy as the fetus relies on maternal thyroxine (T4) exclusively during the first 14 weeks and also throughout gestation. As this hormone is critical to brain and nervous system maturation, low maternal T4 results in low child intelligence quotient. The recommendation for I intake in pregnancy is 250 μg/day to prevent fetal and child brain function impairment. During the past 25 years, the number of countries with I deficiency has reduced to 32; these still include many European developed countries. Sustainability of adequate iodine status must be achieved by continuous monitoring and where this has not been performed I deficiency has often recurred. More randomized controlled trials of iodine supplementation in pregnancy are required in mild iodine-deficient areas to inform public health strategy and subsequent government action on suitable provision of iodine to the population at risk. PMID:25663362

  20. The importance of iodine in public health.

    PubMed

    Lazarus, John H

    2015-08-01

    Iodine (I) deficiency has been known for more than a century and is known to cause cretinism at the extreme end of the spectrum but also, importantly, impaired development and neurocognition in areas of mild deficiency. The WHO has indicated that median urinary iodine of 100-199 μg/l in a population is regarded as indicative of an adequate iodine intake. The understanding of the spectrum of iodine deficiency disorders led to the formation of The International Council for the Control of Iodine Deficiency Disorders which has promulgated the use of household iodized salt and the use of such salt in food processing and manufacture. Iodine deficiency is particularly important in pregnancy as the fetus relies on maternal thyroxine (T4) exclusively during the first 14 weeks and also throughout gestation. As this hormone is critical to brain and nervous system maturation, low maternal T4 results in low child intelligence quotient. The recommendation for I intake in pregnancy is 250 μg/day to prevent fetal and child brain function impairment. During the past 25 years, the number of countries with I deficiency has reduced to 32; these still include many European developed countries. Sustainability of adequate iodine status must be achieved by continuous monitoring and where this has not been performed I deficiency has often recurred. More randomized controlled trials of iodine supplementation in pregnancy are required in mild iodine-deficient areas to inform public health strategy and subsequent government action on suitable provision of iodine to the population at risk.

  1. [Iodine and thyroid: what a clinic should know].

    PubMed

    Santana Lopes, Maria; Jácome de Castro, João; Marcelino, Mafalda; Oliveira, Maria João; Carrilho, Francisco; Limbert, Edward

    2012-01-01

    The World Health Organization considers iodine deficiency as a major worldwide cause of mental and development diseases, estimating that about 13% of the world population is affected by diseases caused by iodine deficiency. Iodine is a trace element necessary for the synthesis of thyroid hormones which, since it cannot be formed by the organism, must be taken regularly with food. Fish and shellfish are generally a good source, because the ocean contains a considerable amount of iodine. On the contrary, plants which grow in iodine-deficient soils are poor in this element, as well as meat and other animal products fed in plants low in iodine. Salt is the best way for iodine supplementation. Cooking the food with iodized salt is a desirable practice because it guarantees the presence of this element. There are also other methods to provide iodine to the general population, such as adding iodine to drinking water or taking supplements of iodine. In pregnancy is recommended iodine supplementation, except in patients with known thyroid disorders. Iodine is an essential component of thyroid hormones (T4 and T3). Inadequate iodine intake leads to inadequate thyroid hormone production. The most important consequences of iodine deficiency, in the general population are goiter and hypothyroidism, and in the severe cases, mental retardation, cretinism and increased neo-natal and infant mortality. The International Council for the Control of Iodine Deficiency Disorders (ICCIDD) formed in 1985, with the only aim of achieving optimal iodine nutrition in the world, in cooperation with UNICEF and WHO. In Portugal, recent studies show significant deficiencies in pregnancy and The Portuguese Society of Endocrinology Diabetes and Metabolism, in partnership with General Directorate of Health, proposed an iodine supplementation during pregnancy with 150-200µg/day. PMID:23069238

  2. Persistent optically induced magnetism in oxygen-deficient strontium titanate.

    PubMed

    Rice, W D; Ambwani, P; Bombeck, M; Thompson, J D; Haugstad, G; Leighton, C; Crooker, S A

    2014-05-01

    Strontium titanate (SrTiO3) is a foundational material in the emerging field of complex oxide electronics. Although its bulk electronic and optical properties are rich and have been studied for decades, SrTiO3 has recently become a renewed focus of materials research catalysed in part by the discovery of superconductivity and magnetism at interfaces between SrTiO3 and other non-magnetic oxides. Here we illustrate a new aspect to the phenomenology of magnetism in SrTiO3 by reporting the observation of an optically induced and persistent magnetization in slightly oxygen-deficient bulk SrTiO3-δ crystals using magnetic circular dichroism (MCD) spectroscopy and SQUID magnetometry. This zero-field magnetization appears below ~18 K, persists for hours below 10 K, and is tunable by means of the polarization and wavelength of sub-bandgap (400-500 nm) light. These effects occur only in crystals containing oxygen vacancies, revealing a detailed interplay between magnetism, lattice defects, and light in an archetypal complex oxide material.

  3. Thiamine deficiency induces anorexia by inhibiting hypothalamic AMPK.

    PubMed

    Liu, M; Alimov, A P; Wang, H; Frank, J A; Katz, W; Xu, M; Ke, Z-J; Luo, J

    2014-05-16

    Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. Thiamine deficiency (TD) can cause a number of disorders in humans, such as Beriberi and Wernicke-Korsakoff syndrome. We demonstrated here that TD caused anorexia in C57BL/6 mice. After feeding a TD diet for 16days, the mice displayed a significant decrease in food intake and an increase in resting energy expenditure (REE), which resulted in a severe weight loss. At the 22nd day, the food intake was reduced by 69% and 74% for male and female mice, respectively in TD group. The REE increased by ninefolds in TD group. The loss of body weight (17-24%) was similar between male and female animals and mainly resulted from the reduction of fat mass (49% decrease). Re-supplementation of thiamine (benfotiamine) restored animal's appetite, leading to a total recovery of body weight. The hypothalamic adenosine monophosphate-activated protein kinase (AMPK) is a critical regulator of food intake. TD inhibited the phosphorylation of AMPK in the arcuate nucleus (ARN) and paraventricular nucleus (PVN) of the hypothalamus without affecting its expression. TD-induced inhibition of AMPK phosphorylation was reversed once thiamine was re-supplemented. In contrast, TD increased AMPK phosphorylation in the skeletal muscle and upregulated the uncoupling protein (UCP)-1 in brown adipose tissues which was consistent with increased basal energy expenditure. Re-administration of thiamine stabilized AMPK phosphorylation in the skeletal muscle as well as energy expenditure. Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight.

  4. MPK3/MPK6 are involved in iron deficiency-induced ethylene production in Arabidopsis

    PubMed Central

    Ye, Lingxiao; Li, Lin; Wang, Lu; Wang, Shoudong; Li, Sen; Du, Juan; Zhang, Shuqun; Shou, Huixia

    2015-01-01

    Iron (Fe) is an essential micronutrient that participates in various biological processes important for plant growth. Ethylene production induced by Fe deficiency plays important roles in plant tolerance to stress induced by Fe deficiency. However, the activation and regulatory mechanisms of 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) genes in this response are not clear. In this study, we demonstrated that Fe deficiency increased the abundance of ACS2, ACS6, ACS7, and ACS11 transcripts in both leaves and roots as well as the abundance of ACS8 transcripts in leaves and ACS9 transcripts in roots. Furthermore, we investigated the role of mitogen-activated protein kinase 3 and 6 (MPK3/MPK6)-regulated ACS2/6 activation in Fe deficiency-induced ethylene production. Our results showed that MPK3/MPK6 transcript abundance and MPK3/MPK6 phosphorylation are elevated under conditions of Fe deficiency. Furthermore, mpk3 and mpk6 mutants show a lesser induction of ethylene production under Fe deficiency and a greater sensitivity to Fe deficiency. Finally, in mpk3, mpk6, and acs2 mutants under conditions of Fe deficiency, induction of transcript expression of the Fe-deficiency response genes FRO2, IRT1, and FIT is partially compromised. Taken together, our results suggest that the MPK3/MPK6 and ACS2 are part of the Fe starvation-induced ethylene production signaling pathway. PMID:26579185

  5. FOLATE DEFICIENCY ENHANCES ARSENIC-INDUCED GENOTOXICITY IN MICE

    EPA Science Inventory

    Folate deficiency increases background levels of DNA damage and can enhance the mutagenicity of chemical agents. Duplicate experiments were performed to investigate the effect of dietary folate deficiency on arsenic induction of micronuclei (MN) in peripheral blood cells. Male C5...

  6. Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism

    SciTech Connect

    Wiersinga, W.M.; Touber, J.L.; Trip, M.D.; van Royen, E.A.

    1986-08-01

    Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. /sup 99m/Tc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and discharge of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I (5.4 +/- 0.8% (+/- SE) at 60 min) was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by /sup 99m/Tc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients.

  7. Recent data on iodine intake in Germany and Europe.

    PubMed

    Gärtner, Roland

    2016-09-01

    Iodine is essential for the synthesis of thyroid hormones. These regulate metabolism, promote growth, development and maturation of all organs, especially the brain. Most iodine is found in oceans and most continental soil and ground water is deficient in iodine. Therefore, around 2 billion individuals are estimated to have insufficient iodine intake and are at risk of iodine deficiency disorders. The best carrier for save iodine supplementation is salt, as the daily intake of salt is mainly constant. Due to the collaboration between international and national organisations and the salt industry, many developing and developed countries introduced universal salt iodization (USI) or have mandatory or voluntary fortification programs. In Germany as in most European countries the use of iodized salt is voluntary not only in household but also in the food industry. Two recent epidemiological surveys in Germany revealed that 33% of children and 32% of adults are still suffering from mild to moderate iodine deficiency. The best surrogate parameter for iodine deficiency is goitre. The goitre prevalence is around 30% in children as well as in adults which is in accordance with the documented iodine deficiency. From other European countries epidemiological derived data on iodine intake are only available from Denmark and Poland. Further efforts are under way to reveal the iodine status with proper methods in all European countries. On this background it might be possible to establish adequate iodine fortification programs in all European countries. PMID:27421794

  8. The Importance of Adequate Iodine during Pregnancy and Infancy.

    PubMed

    Zimmermann, Michael B

    2016-01-01

    Iodine requirements are increased ≥50% during pregnancy. Iodine deficiency during pregnancy can cause maternal and fetal hypothyroidism and impair neurological development of the fetus. The consequences depend upon the timing and severity of the hypothyroidism; the most severe manifestation is cretinism. In iodine-deficient areas, controlled studies have demonstrated that iodine supplementation before or during early pregnancy eliminates new cases of cretinism, increases birth weight, reduces rates of perinatal and infant mortality and generally increases developmental scores in young children by 10-20%. Mild-to-moderate maternal iodine deficiency can cause thyroid dysfunction, but whether it impairs cognitive and/or neurological function in the offspring remains uncertain. In nearly all regions affected by iodine deficiency, salt iodization is the most cost-effective way of delivering iodine and improving maternal and infant health. PMID:27198746

  9. Optically-Induced Persistent Magnetization in Oxygen Deficient Strontium Titanate

    NASA Astrophysics Data System (ADS)

    Crooker, Scott

    2015-03-01

    Interest in electronics and spintronics based on complex oxide materials has exploded in recent years, fueled by the ability to grow atomically-precise heterostructures of various oxides 1. A foundational material in this burgeoning field is strontium titanate, a (nominally) non-magnetic wide-bandgap semiconductor. Owing to its ubiquity in oxide materials science, studies of SrTiO3's interesting dielectric, lattice, and optical properties represent mature research areas. However, renewed interest in SrTiO3 was recently sparked by observations of unexpected spin and magnetization phenomena at interfaces between SrTiO3 and other nonmagnetic oxides 1. The formation and distribution of oxygen vacancies (VO) in SrTiO3 are widely thought to play an essential but as-yet-incompletely understood role in these emergent phenomena. Here we demonstrate a surprising new aspect to the phenomenology of magnetism in SrTiO3 by reporting the observation of an optically-induced and persistent magnetization in slightly oxygen-deficient SrTiO3-δ bulk crystals, using magnetic circular dichroism spectroscopy and optically-coupled SQUID studies 2. This magnetization appears below 18K, persists for hours below 10K, and is tunable via the polarization and wavelength of sub-bandgap (400-500 nm) light. As such, magnetic patterns can be ``written'' into SrTiO3-δ, and subsequently read out, using light alone. This magnetism occurs only in crystals containing VO, and is consistent with a metastable spin polarization of VO-related defect complexes. These data reveal a detailed interplay between magnetism, lattice defects, and light in an archetypal complex oxide material, which may yield new insights into the recent exciting spin physics observed at oxide interfaces.

  10. Intestinal inflammation caused by magnesium deficiency alters basal and oxidative stress-induced intestinal function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Magnesium-deficiency (MgD)induces a systemic pro-inflammatory state. The aim of this study was to determine the effect of MgD on the functional and molecular response to mesenteric ischemia reperfusion. Rats were assigned to 4 groups and placed on magnesium sufficient or deficient diet for 1 or 3 we...

  11. DIETARY FOLATE DEFICIENCY ENHANCES ARSENIC-INDUCED MICRONUCLEUS FORMATION IN MICE

    EPA Science Inventory


    Dietary folate deficiency enhances arsenic-induced micronucleus formation in mice.

    Folate deficiency increases background levels ofDNA damage and can enhance the mutagenicity of chemical agents. Duplicate experiments were performed to investigate the effect of dietary...

  12. Changes in the regulation of iodine crystals and chemical mixtures containing over 2.2 percent iodine. Final rule.

    PubMed

    2007-07-01

    This rulemaking changes the regulation of the listed chemical iodine under the chemical regulatory provisions of the Controlled Substances Act (CSA). The Drug Enforcement Administration (DEA) believes that this action is necessary to remove deficiencies in the existing regulatory controls, which have been exploited by drug traffickers who divert iodine (in the form of iodine crystals and iodine tincture) for the illicit production of methamphetamine in clandestine drug laboratories. This rulemaking moves iodine from List II to List I; reduces the iodine threshold from 0.4 kilograms to zero kilograms; adds import and export regulatory controls; and controls chemical mixtures containing greater than 2.2 percent iodine. This rulemaking establishes regulatory controls that will apply to iodine crystals and iodine chemical mixtures that contain greater than 2.2 percent iodine. This regulation therefore controls iodine crystals and strong iodine tinctures/solutions (e.g., 7 percent iodine) that do not have common household uses and instead have limited application in livestock, horses, and for disinfection of equipment. Household products such as 2 percent iodine tincture/solution and household disinfectants containing iodine complexes will not be adversely impacted by this regulation. Additionally, the final rule exempts transactions of up to one-fluid-ounce (30 ml) of Lugol's Solution. Persons handling regulated iodine materials are required to register with DEA, are subject to the import/export notification requirements of the CSA, and are required to maintain records of all regulated transactions involving iodine regardless of size.

  13. On-line molecular iodine isotopologue detection in gaseous media during spent nuclear fuel reprocessing using a laser-induced fluorescence method

    NASA Astrophysics Data System (ADS)

    Kireev, S. V.; Shnyrev, S. L.

    2015-06-01

    The paper reports on on-line measurement of the {}129{{\\text{I}}2}, 127I129I, and {}127{{\\text{I}}2} concentrations during spent nuclear fuel (SNF) reprocessing using a laser-induced fluorescence method. A He-Ne laser (632.8 nm) was used as a fluorescence excitation source. The detection limits obtained for molecular iodine isotopologue concentrations demonstrate the possibility of using this method for iodine control both in gaseous technological media generated during SNF reprocessing and after passing through the gas purification system (in atmosphere emission).

  14. A model to secure a stable iodine concentration in milk

    PubMed Central

    Trøan, Gisken; Dahl, Lisbeth; Meltzer, Helle Margrete; Abel, Marianne Hope; Indahl, Ulf Geir; Haug, Anna; Prestløkken, Egil

    2015-01-01

    Background Dairy products account for approximately 60% of the iodine intake in the Norwegian population. The iodine concentration in cow's milk varies considerably, depending on feeding practices, season, and amount of iodine and rapeseed products in cow fodder. The variation in iodine in milk affects the risk of iodine deficiency or excess in the population. Objective The first goal of this study was to develop a model to predict the iodine concentration in milk based on the concentration of iodine and rapeseed or glucosinolate in feed, as a tool to securing stable iodine concentration in milk. A second aim was to estimate the impact of different iodine levels in milk on iodine nutrition in the Norwegian population. Design Two models were developed on the basis of results from eight published and two unpublished studies from the past 20 years. The models were based on different iodine concentrations in the fodder combined with either glucosinolate (Model 1) or rapeseed cake/meal (Model 2). To illustrate the impact of different iodine concentrations in milk on iodine intake, we simulated the iodine contribution from dairy products in different population groups based on food intake data in the most recent dietary surveys in Norway. Results The models developed could predict iodine concentration in milk. Cross-validation showed good fit and confirmed the explanatory power of the models. Our calculations showed that dairy products with current iodine level in milk (200 µg/kg) cover 68, 49, 108 and 56% of the daily iodine requirements for men, women, 2-year-old children, and pregnant women, respectively. Conclusions Securing a stable level of iodine in milk by adjusting iodine concentration in different cow feeds is thus important for preventing excess intake in small children and iodine deficiency in pregnant and non-pregnant women. PMID:26689316

  15. Research needs for assessing iodine intake, iodine status, and the effects of maternal iodine supplementation.

    PubMed

    Ershow, Abby G; Goodman, Gay; Coates, Paul M; Swanson, Christine A

    2016-09-01

    The Office of Dietary Supplements of the NIH convened 3 workshops on iodine nutrition in Rockville, Maryland, in 2014. The purpose of the current article is to summarize and briefly discuss a list of research and resource needs developed with the input of workshop participants. This list is composed of the basic, clinical, translational, and population studies required for characterizing the benefits and risks of iodine supplementation, along with related data, analyses, evaluations, methods development, and supporting activities. Ancillary studies designed to use the participant, biological sample, and data resources of ongoing and completed studies (including those not originally concerned with iodine) may provide an efficient, cost-effective means to address some of these research and resource needs. In the United States, the foremost question is whether neurobehavioral development in the offspring of mildly to moderately iodine-deficient women is improved by maternal iodine supplementation during pregnancy. It is important to identify the benefits and risks of iodine supplementation in all population subgroups so that supplementation can be targeted, if necessary, to avoid increasing the risk of thyroid dysfunction and related adverse health effects in those with high iodine intakes. Ultimately, there will be a need for well-designed trials and other studies to assess the impact of maternal supplementation on neurodevelopmental outcomes in the offspring. However, 2 basic information gaps loom ahead of such a study: the development of robust, valid, and convenient biomarkers of individual iodine status and the identification of infant and toddler neurobehavioral development endpoints that are sensitive to mild maternal iodine deficiency during pregnancy and its reversal by supplementation. PMID:27534640

  16. Computer-controlled multi-parameter mapping of 3D compressible flowfields using planar laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Donohue, James M.; Victor, Kenneth G.; Mcdaniel, James C., Jr.

    1993-01-01

    A computer-controlled technique, using planar laser-induced iodine fluorescence, for measuring complex compressible flowfields is presented. A new laser permits the use of a planar two-line temperature technique so that all parameters can be measured with the laser operated narrowband. Pressure and temperature measurements in a step flowfield show agreement within 10 percent of a CFD model except in regions close to walls. Deviation of near wall temperature measurements from the model was decreased from 21 percent to 12 percent compared to broadband planar temperature measurements. Computer-control of the experiment has been implemented, except for the frequency tuning of the laser. Image data storage and processing has been improved by integrating a workstation into the experimental setup reducing the data reduction time by a factor of 50.

  17. Alterations of rat hepatoma cell genomes induced by copper deficiency.

    PubMed

    Renault, E; Deschatrette, J

    1997-01-01

    Copper deficiency imposed on a variant rat hepatoma cell line inhibits cell growth and results in genesis of stable well-differentiated, tumorigenic revertants. The treatment caused a substantial increase in DNA content (up to 20%) of G1 and G2/M cells and inhibition of cell proliferation. This phenomenon was correlated with an enhancement of DNA replication. The excess DNA was unstable and rapidly lost with reinitiation of cell growth and mitosis. Minute and double-minute extrachromosomal material was detected by metaphase analysis, suggesting widespread DNA amplification in copper-deficient conditions. Although transitory, these genetic events were associated with genesis of drug-resistant cells and induction of tumorigenicity of the variant hepatoma cells. The data reveal a novel aspect of the consequences of trace element deficiency.

  18. Thyroid iodine content and serum thyroglobulin: cues to the natural history of destruction-induced thyroiditis

    SciTech Connect

    Smallridge, R.C.; De Keyser, F.M.; Van Herle, A.J.; Butkus, N.E.; Wartofsky, L.

    1986-06-01

    Twenty-eight patients with destructive thyroiditis were followed to study the natural history of healing of thyroid gland injury. All had sequential measurements of thyroidal iodine (/sup 127/I) content by fluorescent scanning (normal mean, 10.1 mg), 17 had serial serum thyroglobulin (Tg) measurements (normal, less than 21 ng/ml), and 13 had perchlorate discharge studies during the recovery phase. Seventeen patients had painful subacute thyroiditis (SAT), 9 had painless thyroiditis with thyrotoxicosis (PTT), and 2 had postpartum thyroiditis with thyrotoxicosis (PPT). Thyroidal iodine content decreased from a mean of 9.8 to a nadir of 3.8 mg in patients with SAT and from 8.5 to a nadir of 3.5 mg in patients with PTT. Mean serum Tg concentrations were highest (approximately 165 ng/ml) in both groups 1-3 months after the onset of symptoms. Abnormalities in both /sup 127/I content and Tg levels persisted for 2 or more yr in some individuals. No patient had detectable Tg antibodies by hemagglutination, but low titers were detected intermittently by sensitive RIA in 5 PTT patients. Microsomal antibodies were positive in only 1 of 16 SAT patients, but in 4 of 7 PTT patients and in both PPT patients. Three patients had positive perchlorate discharge tests (2 of 8 with SAT, 0 of 4 with PTT, and 1 of 1 with PPT). Permanent hypothyroidism occurred in 3 patients (2 with PTT; 1 with SAT and positive antibodies), but did not correlate with perchlorate results. HLA typing and serum immunoglobulin measurements were not useful for predicting the clinical course. These data indicate that several years may be necessary for complete resolution of destructive thyroiditis; many patients have evidence of thyroid injury persisting long after serum thyroid hormone and TSH levels become normal.

  19. [Application of iodine metabolism analysis methods in thyroid diseases].

    PubMed

    Han, Jian-hua; Qiu, Ling

    2013-08-01

    The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases.

  20. [Application of iodine metabolism analysis methods in thyroid diseases].

    PubMed

    Han, Jian-hua; Qiu, Ling

    2013-08-01

    The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases. PMID:23987480

  1. Nutrition: Breast milk--a gateway to iodine-dependent brain development.

    PubMed

    Laurberg, Peter; Andersen, Stine Linding

    2014-03-01

    Iodine from the diet is fundamental for brain development. Via milk, infants receive 40-45% of the iodine in their mother's diet during breastfeeding; however, it is unclear to what extent depot iodine supplements (that is, iodized oil) given to iodine-deficient breastfeeding mothers compares with direct supplementation of the infants.

  2. A novel concept to derive iodine status of human populations from frequency distribution properties of a hair iodine concentration.

    PubMed

    Prejac, J; Višnjević, V; Drmić, S; Skalny, A A; Mimica, N; Momčilović, B

    2014-04-01

    Today, human iodine deficiency is next to iron the most common nutritional deficiency in developed European and underdeveloped third world countries, respectively. A current biological indicator of iodine status is urinary iodine that reflects the very recent iodine exposure, whereas some long term indicator of iodine status remains to be identified. We analyzed hair iodine in a prospective, observational, cross-sectional, and exploratory study involving 870 apparently healthy Croatians (270 men and 600 women). Hair iodine was analyzed with the inductively coupled plasma mass spectrometry (ICP MS). Population (n870) hair iodine (IH) respective median was 0.499μgg(-1) (0.482 and 0.508μgg(-1)) for men and women, respectively, suggesting no sex related difference. We studied the hair iodine uptake by the logistic sigmoid saturation curve of the median derivatives to assess iodine deficiency, adequacy and excess. We estimated the overt iodine deficiency to occur when hair iodine concentration is below 0.15μgg(-1). Then there was a saturation range interval of about 0.15-2.0μgg(-1) (r(2)=0.994). Eventually, the sigmoid curve became saturated at about 2.0μgg(-1) and upward, suggesting excessive iodine exposure. Hair appears to be a valuable and robust long term biological indicator tissue for assessing the iodine body status. We propose adequate iodine status to correspond with the hair iodine (IH) uptake saturation of 0.565-0.739μgg(-1) (55-65%).

  3. Discovery and Early Uses of Iodine

    NASA Astrophysics Data System (ADS)

    Rosenfeld, Louis

    2000-08-01

    The ancient Chinese recognized goiter and the therapeutic effects of burnt sponge and seaweed in reducing its size or causing its disappearance. The modern use of iodine in the prevention of goiter dates from 1830, when it was proposed that goiter is an iodine deficiency disease due to lack of iodine in the water supply. But unfavorable symptoms of iodism were frequent owing to overenthusiastic use and overdose of iodine. Consequently, iodide prophylaxis was discredited and abandoned. The presence of iodine in organic combination as a normal constituent of the thyroid was established in 1896 and the use of iodine in treatment and prevention of goiter was revived. In 1917 the general use of iodized salt in goitrous areas was shown to be effective in preventing simple endemic goiter.

  4. Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis.

    PubMed

    Romualdo, Guilherme Ribeiro; Goto, Renata Leme; Henrique Fernandes, Ana Angélica; Cogliati, Bruno; Barbisan, Luis Fernando

    2016-10-01

    Although there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect.

  5. Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis.

    PubMed

    Romualdo, Guilherme Ribeiro; Goto, Renata Leme; Henrique Fernandes, Ana Angélica; Cogliati, Bruno; Barbisan, Luis Fernando

    2016-10-01

    Although there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect. PMID:27544374

  6. Genetic AVP deficiency abolishes cold-induced diuresis but does not attenuate cold-induced hypertension.

    PubMed

    Sun, Zhongjie

    2006-06-01

    Chronic cold exposure causes hypertension and diuresis. The aim of this study was to determine whether vasopressin (AVP) plays a role in cold-induced hypertension and diuresis. Two groups of Long-Evans (LE) and two groups of homozygous AVP-deficient Brattleboro (VD) rats were used. Blood pressure (BP) was not different among the four groups during a 2-wk control period at room temperature (25 degrees C, warm). After the control period, one LE group and one VD group were exposed to cold (5 degrees C); the remaining groups were kept at room temperature. BP and body weight were measured weekly during exposure to cold. Food intake, water intake, urine output, and urine osmolality were measured during weeks 1, 3, and 5 of cold exposure. At the end of week 5, all animals were killed and blood was collected for measurement of plasma AVP. Kidneys were removed for measurement of renal medulla V2 receptor mRNA and aquaporin-2 (AQP-2) protein expression. BP of LE and VD rats increased significantly by week 2 of cold exposure and reached a high level by week 5. BP elevations developed at approximately the same rate and to the same degree in LE and VD rats. AVP deficiency significantly increased urine output and solute-free water clearance and decreased urine osmolality. Chronic cold exposure increased urine output and solute-free water clearance and decreased urine osmolality in LE rats, indicating that cold exposure caused diuresis in LE rats. Cold exposure failed to affect these parameters in VD rats, suggesting that the AVP system is responsible for cold-induced diuresis. Cold exposure did not alter plasma AVP in LE rats. Renal medulla V2 receptor mRNA and AQP-2 protein expression levels were decreased significantly in the cold-exposed LE rats, suggesting that cold exposure inhibited renal V2 receptors and AVP-inducible AQP-2 water channels. We conclude that 1) AVP may not be involved in the pathogenesis of cold-induced hypertension, 2) the AVP system plays a critical role

  7. Chronic Pseudomonas aeruginosa infection-induced chronic bronchitis and emphysematous changes in CCSP-deficient mice

    PubMed Central

    Matsumoto, Takemasa; Fujita, Masaki; Hirano, Ryosuke; Uchino, Junji; Tajiri, Yukari; Fukuyama, Satoru; Morimoto, Yasuo; Watanabe, Kentaro

    2016-01-01

    The club cell secretory protein (CCSP) is a regulator of lung inflammation following acute respiratory infection or lung injury. Recently, the relationship between CCSP and COPD has been reported. Since COPD results from an abnormal inflammatory response, we hypothesized that CCSP could have a protective role against chronic inflammation-induced lung damage. To address this issue, the pathophysiology of chronic lung inflammation induced by Pseudomonas aeruginosa in CCSP-deficient mice was determined. A tube of 5 mm in length was soaked in a fluid containing P. aeruginosa (PAO01 strain) for 1 week and inserted into the trachea of CCSP-deficient mice. One week later, P. aeruginosa was administered into the trachea. Five weeks after insertion of tube, the mice were sacrificed. Bronchoalveolar lavage fluids were collected to determine the bacterial growth, and the lung histology and physiology were also examined. P. aeruginosa was continuously detected in bronchoalveolar lavage fluids during the study. Neutrophils were increased in the bronchoalveolar lavage fluids from the CCSP-deficient mice in comparison to wild-type mice. A histological study demonstrated chronic inflammation around bronchus, serious bronchial stenosis, and alveolar enlargement in the CCSP-deficient mice. The lung physiology study demonstrated an increase in the lung compliance of the CCSP-deficient mice. Chronic P. aeruginosa inflammation resulted in chronic bronchitis and emphysematous changes in the CCSP-deficient mice. CCSP could play an important role in protecting the host from the chronic inflammation-induced lung damage. PMID:27703342

  8. [Pathology of placenta of rats induced by fatty acid deficiency].

    PubMed

    Glocker, T M

    2000-01-01

    Lipids are important cell components, both from the structural and the functional point of view. Besides, they intervene in transporting functions, cell recognition and immunity. Essential Fatty Acids (EFA) are important for the functional and structural maintenance of animal organisms. In our laboratory, it was demonstrated that one group of pregnant rats fed on an EFA deficient diet, and other group of rats fed on the same diet but with 5% of corn oil (rich in linoleic acid) showed alterations on the development of the metrial gland. In the present work, 57 female rats of a Wistar strain were fed since weaning with one of the following diets: EFAD: deficient in essential fatty acids, COD: EFAD + 5% corn oil (linoleic acid sufficient but alpha-linoleic acid deficient); SAD: EFAD + 5% soy oil (both EFA sufficient) and CD: commercial diet. After 3 months the animals were sacrificed on the 13 th. day of gestation. Uteru's horns were dissected and the implantation sities were fixed on formol and embebbed in parafin. The observations were carried out with H/E coloured cross-sections and the corialantoidea placenta, the cities of implantations and the sitios of reabsortions were studied. The metrial gland of DAGE and DAM rats presented structural modifications compared to DC rats. The most relevant findings were: indifferentiation of the granulated metrial gland cells and an increase in the amount of connective tissue. In DAS rats, on the contrary, the aspect of the metrial gland was similar to the observed in the DC group. In the DAGE and the DAM groups Labyrinthium was enlarged with vascular septum group. Mean while DAS was similar to group DC (thin and vascular). Differences in the cities of implantations and reabsortions were not detected. The present results suggest that alpha-linolenico acid is essential for the rat placenta to reach normal development.

  9. Dietary zinc deficiency exaggerates ethanol-induced liver injury in mice: involvement of intrahepatic and extrahepatic factors.

    PubMed

    Zhong, Wei; Zhao, Yantao; Sun, Xinguo; Song, Zhenyuan; McClain, Craig J; Zhou, Zhanxiang

    2013-01-01

    Clinical studies have demonstrated that alcoholics have a lower dietary zinc intake compared to health controls. The present study was undertaken to determine the interaction between dietary zinc deficiency and ethanol consumption in the pathogenesis of alcoholic liver disease. C57BL/6N mice were subjected to 8-week feeding of 4 experimental liquid diets: (1) zinc adequate diet, (2) zinc adequate diet plus ethanol, (3) zinc deficient diet, and (4) zinc deficient diet plus ethanol. Ethanol exposure with adequate dietary zinc resulted in liver damage as indicated by elevated plasma alanine aminotransferase level and increased hepatic lipid accumulation and inflammatory cell infiltration. Dietary zinc deficiency alone increased hepatic lipid contents, but did not induce hepatic inflammation. Dietary zinc deficiency showed synergistic effects on ethanol-induced liver damage. Dietary zinc deficiency exaggerated ethanol effects on hepatic genes related to lipid metabolism and inflammatory response. Dietary zinc deficiency worsened ethanol-induced imbalance between hepatic pro-oxidant and antioxidant enzymes and hepatic expression of cell death receptors. Dietary zinc deficiency exaggerated ethanol-induced reduction of plasma leptin, although it did not affect ethanol-induced reduction of white adipose tissue mass. Dietary zinc deficiency also deteriorated ethanol-induced gut permeability increase and plasma endotoxin elevation. These results demonstrate, for the first time, that dietary zinc deficiency is a risk factor in alcoholic liver disease, and multiple intrahepatic and extrahepatic factors may mediate the detrimental effects of zinc deficiency.

  10. Metformin administration induces hepatotoxic effects in paraoxonase-1-deficient mice.

    PubMed

    García-Heredia, Anabel; Riera-Borrull, Marta; Fort-Gallifa, Isabel; Luciano-Mateo, Fedra; Cabré, Noemí; Hernández-Aguilera, Anna; Joven, Jorge; Camps, Jordi

    2016-04-01

    Metformin is the first-line pharmacological treatment of diabetes. In these patients, metformin reduces body weight and decreases the risk of diabetes-related complications such as cardiovascular disease. However, whether metformin elicits beneficial effects on liver histology is a controversial issue and, as yet, there is no consensus. Paraoxonase-1 (PON1), an enzyme synthesized mainly by the liver, degrades lipid peroxides and reduces oxidative stress. PON1 activities are decreased in chronic liver diseases. We evaluated the effects of metformin in the liver of PON1-deficient mice which, untreated, present a mild degree of liver steatosis. Metformin administration aggravated inflammation in animals given a standard mouse chow and in those fed a high-fat diet. Also, it was associated with a higher degree of steatosis in animals fed a standard chow diet. This report is a cautionary note regarding the prescription of metformin for the treatment of diabetes in patients with concomitant liver impairment.

  11. FDA regulations regarding iodine addition to foods and labeling of foods containing added iodine.

    PubMed

    Trumbo, Paula R

    2016-09-01

    The US Food and Drug Administration (FDA) regulates the addition of iodine to infant formulas, the iodization of salt, and the addition of salt and iodine to foods. The required amount of iodine in infant formulas is based on caloric content, and the label must provide the iodine content per 100 kcal. Cuprous iodide and potassium iodide may be added to table salt as a source of dietary iodine at a maximum amount of 0.01%; if added, the label must indicate that the salt is iodized. Table salt to which iodine has not been added must bear the statement, "This salt does not supply iodide, a necessary nutrient." If a nutrient is to be appropriately added to a food for the purpose of correcting a dietary insufficiency, there should be sufficient scientific information available to demonstrate a nutritional deficiency and/or identify a public health problem. Furthermore, the population groups that would benefit from the proposed fortification should be identified. If iodine is added to a food, the percent Daily Value of iodine must be listed. There are no FDA regulations governing ingredient standards for dietary supplements. As a result, some dietary supplements include iodine and others do not. If a supplement contains iodine, the Supplement Facts label must list iodine as a nutrient ingredient. If iodine is not listed on the Supplement Facts label, then it has not been added. There are similarities between the FDA, which establishes US food regulations and policies, and the Codex Alimentarius (Codex), which develops international food standards and guidelines under the aegis of the FAO and the WHO. Both the FDA and Codex call for the labeling of table salt to indicate fortification with iodine, voluntary labeling of iodine on foods, and a Daily Value (called a Nutrient Reference Value by Codex) of 150 μg for iodine. PMID:27534626

  12. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status.

    PubMed

    Pearce, Elizabeth N; Caldwell, Kathleen L

    2016-09-01

    The accurate assessment of population iodine status is necessary to inform public health policies and clinical research on iodine nutrition, particularly the role of iodine adequacy in normal neurodevelopment. Urinary iodine concentration (UIC) directly reflects dietary iodine intake and is the most common indicator used worldwide to assess population iodine status. The CDC established the Ensuring the Quality of Iodine Procedures program in 2001 to provide laboratories that measure urinary iodine with an independent assessment of their analytic performance; this program fosters improvement in the assessment of UIC. Clinical laboratory tests of thyroid function (including serum concentrations of the pituitary hormone thyrotropin and the thyroid hormones thyroxine and triiodothyronine) are sometimes used as indicators of iodine status, although such use is often problematic. Even in severely iodine-deficient regions, there is a great deal of intraindividual variation in the ability of the thyroid to adapt. In most settings and in most population subgroups other than newborns, thyroid function tests are not considered sensitive indicators of population iodine status. However, the thyroid-derived protein thyroglobulin is increasingly being used for this purpose. Thyroglobulin can be measured in either serum or dried blood spot (DBS) samples. The use of DBS samples is advantageous in resource-poor regions. Improved methodologies for ascertaining maternal iodine status are needed to facilitate research on developmental correlates of iodine status. Thyroglobulin may prove to be a useful biomarker for both maternal and neonatal iodine status, but validated assay-specific reference ranges are needed for the determination of iodine sufficiency in both pregnant women and neonates, and trimester-specific ranges are possibly needed for pregnant women. UIC is currently a well-validated population biomarker, but individual biomarkers that could be used for research, patient care

  13. Amniotic fluid iodine concentrations do not vary in pregnant women with varying iodine intake.

    PubMed

    García-Fuentes, Eduardo; Gallo, Manuel; García, Laureano; Prieto, Stephanie; Alcaide-Torres, Javier; Santiago, Piedad; Velasco, Inés; Soriguer, Federico

    2008-06-01

    Iodine deficiency is an important clinical and public health problem. Its prevention begins with an adequate intake of iodine during pregnancy. International agencies recommend at least 200 microg iodine per d for pregnant women. We assessed whether iodine concentrations in the amniotic fluid of healthy pregnant women are independent of iodine intake. This cross-sectional, non-interventional study included 365 consecutive women who underwent amniocentesis to determine the fetal karyotype. The amniocentesis was performed with abdominal antisepsis using chlorhexidine. The iodine concentration was measured in urine and amniotic fluid. The study variables were the intake of iodized salt and multivitamin supplements or the prescription of a KI supplement. The mean level of urinary iodine was 139.0 (SD 94.5) microg/l and of amniotic fluid 15.81 (SD 7.09) microg/l. The women who consumed iodized salt and those who took a KI supplement had significantly higher levels of urinary iodine than those who did not (P = 0.01 and P = 0.004, respectively). The urinary iodine levels were not significantly different in the women who took a multivitamin supplement compared with those who did not take this supplement, independently of iodine concentration or multivitamin supplement. The concentrations of iodine in the amniotic fluid were similar, independent of the dietary iodine intake. Urine and amniotic fluid iodine concentrations were weakly correlated, although the amniotic fluid values were no higher in those women taking a KI supplement. KI prescription at recommended doses increases the iodine levels in the mother without influencing the iodine levels in the amniotic fluid.

  14. EURRECA-Estimating iodine requirements for deriving dietary reference values.

    PubMed

    Ristić-Medić, Danijela; Novaković, Romana; Glibetić, Maria; Gurinović, Mirjana

    2013-01-01

    Iodine is an essential component of thyroid hormones, and current recommendations for intake are based on urinary iodine excretion, assessment of thyroid size, thyroidal iodine accumulation and turnover, radioactive iodine uptake, balance studies, and epidemiological studies. Dietary iodine is rapidly and almost completely absorbed. The prevalence of inadequate iodine intake is high: 29% of the world's population lives in iodine-deficient areas and 44% of Europe remains mildly iodine deficient. To assess current data and update evidence for setting dietary recommendations for iodine, the EURRECA Network of Excellence has undertaken systematic review and evaluation of (i) the usefulness of iodine status biomarkers (ii) the relationship between iodine status biomarkers and dietary iodine intake, and (iii) the relationship between iodine intake and health outcomes (endemic goiter, hypothyroidism, and cognitive function). This review summarizes the main research outputs: the key findings of the literature review, results of the meta-analyses, and discussion of the main conclusions. Currently, data for relevant intake-status-health relationships for iodine are limited, particularly for population groups such as children under two years, pregnant women, and the elderly. The EURRECA Network developed best practice guidelines for the identification of pertinent iodine studies based on a systematic review approach. This approach aimed to identify comparable data, suitable for meta-analysis, for different countries and across all age ranges. When new data are available, the EURRECA Network best practice guidelines will provide a better understanding of iodine requirements for different health outcomes which could be used to set evidence-based dietary iodine recommendations for optimal health. PMID:23952087

  15. A study of myocardial muscarinic receptors in streptozotocin-induced diabetic rats using iodine-123 N-methyl-4-iododexetimide.

    PubMed

    Mardon, K; Kassiou, M; Katsifis, A; Najdovski, L

    1999-07-01

    In previous studies we have shown that iodine-123 N-methyl-4-iododexetimide ([123I]MIDEX) is a suitable single-photon emission tomography radiotracer for the characterisation of myocardial muscarinic acetylcholine receptors (m-AChR) in the normal state. It has been demonstrated that m-AChR are altered as a consequence of diabetes. The aim of the present study was to examine myocardial m-AChR density using [123I]MIDEX in streptozotocin (STZ)-induced diabetic rats. In vitro binding experiments were conducted on left and right ventricle and atrium homogenate membranes of 1-week, 5-week and 10-week STZ-induced diabetic and aged-matched normal rats. The m-AChR densities (Bmax values), as determined by saturation experiments with [123I]MIDEX, revealed no difference in left and right ventricles or atrium in 1-week and 5-week STZ-diabetic rats when compared with normal rats. However, the 10-week STZ-diabetic group revealed a 39% (P<0.001) decrease in m-AChR density in atrium with no change in left and right ventricles. The equilibrium dissociation constant (Kd values) was similar in all groups. In vitro binding autoradiography revealed a 40% decrease in m-AChR density in atrium in the same 10-week diabetic rats. No statistically significant difference was found in 1-week and 5-week diabetic rats compared with normals. Ex vivo autoradiography showed a 50% decrease in [123I]MIDEX uptake in atrium in 5-week diabetic rats and a 60% decrease in 10-week diabetic rats. These results demonstrate the ability of the single-photon agent [123I]MIDEX to measure in vitro and ex vivo alterations in myocardial m-AChR density observed in STZ-induced diabetic rats. PMID:10398822

  16. Delayed auditory conduction in diabetes: is metformin-induced vitamin B12 deficiency responsible?

    PubMed Central

    Khattar, Deepti; Khaliq, Farah; Vaney, Neelam; Madhu, Sri Venkata

    2016-01-01

    Summary The present study aims to evaluate the functional integrity of the auditory pathway in patients with diabetes taking metformin. A further aim is to assess its association with vitamin B12 deficiency induced by metformin. Thirty diabetics taking metformin and 30 age-matched non-diabetic controls were enrolled. Stimulus-related potentials and vitamin B12 levels were evaluated in all the subjects. The diabetics showed deficient vitamin B12 levels and delayed wave III latency and III–V interpeak latency in the right ear and delayed Na and Pa wave latencies in the left ear compared with the controls. The dose and duration of metformin showed no association with the stimulus-related potentials. Therefore, although vitamin B12 levels were deficient and auditory conduction impairment was present in the diabetics on metformin, this impairment cannot be attributed to the vitamin B12 deficiency. PMID:27358222

  17. Iodine Satellite

    NASA Technical Reports Server (NTRS)

    Kamhawi, Hani; Dankanich, John; Martinez, Andres; Petro, Andrew

    2015-01-01

    The Iodine Satellite (iSat) spacecraft will be the first CubeSat to demonstrate high change in velocity from a primary propulsion system by using Hall thruster technology and iodine as a propellant. The mission will demonstrate CubeSat maneuverability, including plane change, altitude change and change in its closest approach to Earth to ensure atmospheric reentry in less than 90 days. The mission is planned for launch in fall 2017. Hall thruster technology is a type of electric propulsion. Electric propulsion uses electricity, typically from solar panels, to accelerate the propellant. Electric propulsion can accelerate propellant to 10 times higher velocities than traditional chemical propulsion systems, which significantly increases fuel efficiency. To enable the success of the propulsion subsystem, iSat will also demonstrate power management and thermal control capabilities well beyond the current state-of-the-art for spacecraft of its size. This technology is a viable primary propulsion system that can be used on small satellites ranging from about 22 pounds (10 kilograms) to more than 1,000 pounds (450 kilograms). iSat's fuel efficiency is ten times greater and its propulsion per volume is 100 times greater than current cold-gas systems and three times better than the same system operating on xenon. iSat's iodine propulsion system consists of a 200 watt (W) Hall thruster, a cathode, a tank to store solid iodine, a power processing unit (PPU) and the feed system to supply the iodine. This propulsion system is based on a 200 W Hall thruster developed by Busek Co. Inc., which was previously flown using xenon as the propellant. Several improvements have been made to the original system to include a compact PPU, targeting greater than 80 percent reduction in mass and volume of conventional PPU designs. The cathode technology is planned to enable heaterless cathode conditioning, significantly increasing total system efficiency. The feed system has been designed to

  18. Phosphate Deficiency Induces the Jasmonate Pathway and Enhances Resistance to Insect Herbivory1[OPEN

    PubMed Central

    Glauser, Gaétan

    2016-01-01

    During their life cycle, plants are typically confronted by simultaneous biotic and abiotic stresses. Low inorganic phosphate (Pi) is one of the most common nutrient deficiencies limiting plant growth in natural and agricultural ecosystems, while insect herbivory accounts for major losses in plant productivity and impacts ecological and evolutionary changes in plant populations. Here, we report that plants experiencing Pi deficiency induce the jasmonic acid (JA) pathway and enhance their defense against insect herbivory. Pi-deficient Arabidopsis (Arabidopsis thaliana) showed enhanced synthesis of JA and the bioactive conjugate JA-isoleucine, as well as activation of the JA signaling pathway, in both shoots and roots of wild-type plants and in shoots of the Pi-deficient mutant pho1. The kinetics of the induction of the JA signaling pathway by Pi deficiency was influenced by PHOSPHATE STARVATION RESPONSE1, the main transcription factor regulating the expression of Pi starvation-induced genes. Phenotypes of the pho1 mutant typically associated with Pi deficiency, such as high shoot anthocyanin levels and poor shoot growth, were significantly attenuated by blocking the JA biosynthesis or signaling pathway. Wounded pho1 leaves hyperaccumulated JA/JA-isoleucine in comparison with the wild type. The pho1 mutant also showed an increased resistance against the generalist herbivore Spodoptera littoralis that was attenuated in JA biosynthesis and signaling mutants. Pi deficiency also triggered increased resistance to S. littoralis in wild-type Arabidopsis as well as tomato (Solanum lycopersicum) and Nicotiana benthamiana, revealing that the link between Pi deficiency and enhanced herbivory resistance is conserved in a diversity of plants, including crops. PMID:27016448

  19. Folate Deficiency Induces Neurodegeneration and Brain Dysfunction in Mice Lacking Uracil DNA Glycosylase

    PubMed Central

    Kronenberg, Golo; Harms, Christoph; Sobol, Robert W.; Cardozo-Pelaez, Fernando; Linhart, Heinz; Winter, Benjamin; Balkaya, Mustafa; Gertz, Karen; Gay, Shanna B.; Cox, David; Eckart, Sarah; Ahmadi, Michael; Juckel, Georg; Kempermann, Gerd; Hellweg, Rainer; Sohr, Reinhard; Hörtnagl, Heide; Wilson, Samuel H.; Jaenisch, Rudolf

    2008-01-01

    Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung−/−) versus wild-type controls. Folate depletion increased nuclear mutation rates in Ung−/− embryonic fibroblasts, and conferred death of cultured Ung−/− hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons in Ung−/− but not Ung+/+ mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated in Ung−/− mice. Independent of Ung genotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency. PMID:18614692

  20. Iodine concentration of milk in a dose-response study with dairy cows and implications for consumer iodine intake.

    PubMed

    Schöne, Friedrich; Leiterer, Matthias; Lebzien, Peter; Bemmann, Doreen; Spolders, Markus; Flachowsky, Gerhard

    2009-01-01

    Most feed is poor in iodine and iodine supplementation of cow's diets must guarantee milk iodine concentrations for humans that contribute to prevention of the deficiency and minimize the risk of exceeding an upper limit of iodine intake. Five Holstein cows were fed four iodine doses (via Ca(Iota O(3))(2).6H(2)O). In four sequential 14-d periods, doses of 0.2 (basal diet), 1.3, 5.1, and 10.1 mg iodine kg(-1) diet dry matter (DM) were administered. Samples of milk were collected during each period; blood was also sampled from each cow for each iodine dosage. In an 18-d depletion period, a non-supplemented diet was provided. Iodine was determined by inductively coupled plasma-mass spectrometry. The iodine content of milk and serum reflected the iodine dosages in feed significantly. The levels for the four doses tested in milk were 101+/-32, 343+/-109, 1215+/-222, and 2762+/-852 microg iodine kg(-1). The total amount of iodine in milk per day was 30-40% of ingested supplemental iodine. Omitting additional iodine resulted in a short-term reduction of serum and milk iodine following an exponential decay function. The iodine supplementation of 0.5-1.5 mg kg(-1) diet DM represents the requirement of the cow, resulting in 100-300 microg iodine L(-1) milk, which optimally contributes to human supply. The maximum dietary levels of former and present EU legislations (10 and 5 mg iodine kg(-1) cow feed) increase the risk of iodine excess in humans.

  1. Iodine supplementation and the prevention of cretinism.

    PubMed

    Dunn, J T

    1993-03-15

    Normal development of the CNS requires adequate thyroid hormone exposure. Since iodine is an essential component of the thyroid hormone molecule, its deficiency during fetal development can cause hypothyroidism and irreversible mental retardation. The full-blown syndrome, called cretinism, includes deaf-mutism, short stature, spasticity, and profound mental retardation. The clinical spectrum can vary in degree and combination of these features. Screening programs in iodine-deficient countries show that up to 10% of neonates have elevated serum TSH levels, putting them at theoretical risk for permanent brain damage. About one billion people worldwide risk the consequences of iodine deficiency, all of which can be prevented by adequate maternal and infant iodine nutrition. Iodized salt is usually the preferred prophylactic vehicle, but iodized vegetable oil, iodized water, and iodine tablets are also occasionally used. The United Nations and the heads of state of most countries have pledged the virtual elimination of iodine deficiency by the year 2000. This goal is technically feasible if pursued with sufficient vigor and resources. PMID:8494259

  2. Selenium deficiency induced by zinc deprivation in a crustacean

    SciTech Connect

    Keating, K.I.; Caffrey, P.B. )

    1989-08-01

    For intact daphnids reared in circumstances of controlled trace element exposure, one consequence of insufficient zinc (Zn) is an increased demand on the animal's pool of available selenium (Se). This demand is manifested by the type of cuticle deterioration associated with Se deficiency and by a depression of reproduction. In the presence of 25 parts per billion (ppb) Zn, 1 ppb Se eliminates these symptoms. In the absence of detectable Zn, 5 ppb Se eliminates overt cuticle damage and substantially increases reproduction. A shortening of life span resulting from Zn deprivation is not ameliorated by Se addition. The authors suggest that the interplay between Zn and Se concentrations reflects an underlying interplay between interdependent, but distinct, metabolic pathways; i.e., (for Se) glutathione peroxidase and (for Zn) Cu,Zn-superoxide dismutase--each offering protection against free radical damage. Because they are not necessarily localized in a given tissue, the key to recognition of such subtle, complex trace nutrient interactions has been use of intact animals in circumstances of control previously attainable only in tissue cultures.

  3. Appropriate iodine nutrition in Iran: 20 years of success.

    PubMed

    Delshad, Hossein; Mehran, Ladan; Azizi, Fereidoun

    2010-01-01

    Iodine is a trace element in the human body, its only known function is the synthesis of thyroid hormones. Effects of iodine deficiency, termed iodine deficiency disorders (IDD), include endemic goiter, hypothyroidism, cretinism, decreased fertility rate, increased infant mortality and mental retardation. 2.2 billion people worldwide are at risk for IDD. Of these, 30-70% have goiter and 1-10% have cretinism. Two decades ago the I.R. Iran was among the countries most severely affected by iodine deficiency, but during the last two decades has made much progress in the development of universal salt iodization strategies and IDD prevention, and since 1996 meets all WHO/UNICEF/ICCIDD criteria for the sustainable elimination of iodine deficiency. PMID:21287473

  4. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    SciTech Connect

    Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali; Hemati, Simin

    2015-07-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.

  5. Evaluation of bromine and iodine content of milk whey proteins combining digestion by microwave-induced combustion and ICP-MS determination.

    PubMed

    da Silva, Sabrina Vieira; Picoloto, Rochele Sogari; Flores, Erico Marlon Moraes; Wagner, Roger; dos Santos Richards, Neila Silvia Pereira; Barin, Juliano Smanioto

    2016-01-01

    The bromine and iodine content of whey protein concentrate (WPC), hydrolysate (WPH), and isolate (WPI) was evaluated combining microwave-induced combustion (MIC) digestion with inductively coupled plasma mass spectrometry (ICP-MS) determination. MIC digestion allowed the decomposition of up to 500 mg of samples using diluted NH4OH solution (25 mmol L(-1)) for absorption of analytes, assuring the compatibility with ICP-MS determination. Accuracy was evaluated using milk powder certified reference material (NIST 8435) with good agreements for Br and I (102% and 105%, respectively). For Br and I, the limit of quantification obtained by ICP-MS was 7 and 281 times lower in comparison with ion chromatography determination, respectively. Iodine could be enriched in whey protein production and up to 70% of the tolerable upper intake level was found, thus revealing the need to monitor it in whey proteins. On the other hand, the concentration of Br was below its acceptable daily intake.

  6. Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation

    PubMed Central

    Wong, Carmen P.; Rinaldi, Nicole A.; Ho, Emily

    2015-01-01

    Scope Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age-related immune defects, including chronic inflammation, coincide with declining zinc status. Methods and results An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency up-regulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, that coincided with increased IL1β and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals. Conclusion Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation. PMID:25656040

  7. Discovering the role of mitochondria in the iron deficiency-induced metabolic responses of plants.

    PubMed

    Vigani, Gianpiero

    2012-01-01

    In plants, iron (Fe) deficiency-induced chlorosis is a major problem, affecting both yield and quality of crops. Plants have evolved multifaceted strategies, such as reductase activity, proton extrusion, and specialised storage proteins, to mobilise Fe from the environment and distribute it within the plant. Because of its fundamental role in plant productivity, several issues concerning Fe homeostasis in plants are currently intensively studied. The activation of Fe uptake reactions requires an overall adaptation of the primary metabolism because these activities need the constant supply of energetic substrates (i.e., NADPH and ATP). Several studies concerning the metabolism of Fe-deficient plants have been conducted, but research focused on mitochondrial implications in adaptive responses to nutritional stress has only begun in recent years. Mitochondria are the energetic centre of the root cell, and they are strongly affected by Fe deficiency. Nevertheless, they display a high level of functional flexibility, which allows them to maintain the viability of the cell. Mitochondria represent a crucial target of studies on plant homeostasis, and it might be of interest to concentrate future research on understanding how mitochondria orchestrate the reprogramming of root cell metabolism under Fe deficiency. In this review, I summarise what it is known about the effect of Fe deficiency on mitochondrial metabolism and morphology. Moreover, I present a detailed view of the possible roles of mitochondria in the development of plant responses to Fe deficiency, integrating old findings with new and discussing new hypotheses for future investigations.

  8. Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice

    PubMed Central

    McKinley, Laura; Kim, Jiyoun; Bolgos, Gerald L; Siddiqui, Javed; Remick, Daniel G

    2006-01-01

    Background Previous genetic analysis has shown that a deletion in the complement component 5 gene-coding region renders mice more susceptible to allergen-induced airway hyperresponsiveness (AHR) due to reduced IL-12 production. We investigated the role of complement in a murine model of asthma-like pulmonary inflammation. Methods In order to evaluate the role of complement B10 mice either sufficient or deficient in C5 were studied. Both groups of mice immunized and challenged with a house dust extract (HDE) containing high levels of cockroach allergens. Airways hyper-reactivity was determined with whole-body plesthysmography. Bronchoalveolar lavage (BAL) was performed to determine pulmonary cellular recruitment and measure inflammatory mediators. Lung homogenates were assayed for mediators and plasma levels of IgE determined. Pulmonary histology was also evaluated. Results C5-deficient mice showed enhanced AHR to methylcholine challenge, 474% and 91% increase above baseline Penh in C5-deficient and C5-sufficient mice respectively, p < 0.001. IL-12 levels in the lung homogenate (LH) were only slightly reduced and BAL IL-12 was comparable in C5-sufficient and C5-deficient mice. However, C5-deficient mice had significantly higher cysteinyl-leukotriene levels in the BAL fluid, 1913 +/- 246 pg/ml in C5d and 756 +/- 232 pg/ml in C5-sufficient, p = 0.003. Conclusion These data demonstrate that C5-deficient mice show enhanced AHR due to increased production of cysteinyl-leukotrienes. PMID:17044927

  9. Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.

    PubMed

    Grin'kina, Natalia M; Karnabi, Eddy E; Damania, Dushyant; Wadgaonkar, Sunil; Muslimov, Ilham A; Wadgaonkar, Raj

    2012-01-01

    The pathogenesis of inflammation in the central nervous system (CNS), which contributes to numerous neurodegenerative diseases and results in encephalopathy and neuroinflammation, is poorly understood. Sphingolipid metabolism plays a crucial role in maintaining cellular processes in the CNS, and thus mediates the various pathological consequences of inflammation. For a better understanding of the role of sphingosine kinase activation during neuroinflammation, we developed a bacterial lipopolysaccharide (LPS)-induced brain injury model. The onset of the inflammatory response was observed beginning 4 hours after intracerebral injection of LPS into the lateral ventricles of the brain. A comparison of established neuroinflammatory parameters such as white matter rarefactions, development of cytotoxic edema, astrogliosis, loss of oligodendrocytes, and major cytokines levels in wild type and knockout mice suggested that the neuroinflammatory response in SphK1-/- mice was significantly upregulated. At 6 hours after intracerebroventricular injection of LPS in SphK1-/- mice, the immunoreactivity of the microglia markers and astrocyte marker glial fibrillary acidic protein (GFAP) were significantly increased, while the oligodendrocyte marker O4 was decreased compared to WT mice. Furthermore, western blotting data showed increased levels of GFAP. These results suggest that SphK1 activation is involved in the regulation of LPS induced brain injury. RESEARCH HIGHLIGHTS: • Lipopolysaccharide (LPS) intracerebral injection induces severe neuroinflammation. • Sphingosine kinase 1 deletion worsens the effect of the LPS. • Overexpression of SphK1 might be a potential new treatment approach to neuroinflammation.

  10. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    PubMed

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

  11. TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

    PubMed

    An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

    2012-11-01

    Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

  12. Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production

    NASA Astrophysics Data System (ADS)

    Sugita, Kazunari; Ikenouchi-Sugita, Atsuko; Nakayama, Yasuko; Yoshioka, Haruna; Nomura, Takashi; Sakabe, Jun-Ichi; Nakahigashi, Kyoko; Kuroda, Etsushi; Uematsu, Satoshi; Nakamura, Jun; Akira, Shizuo; Nakamura, Motonobu; Narumiya, Shuh; Miyachi, Yoshiki; Tokura, Yoshiki; Kabashima, Kenji

    2013-10-01

    Pellagra is a photosensitivity syndrome characterized by three ``D's'': diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE2 production via induction of ROS formation.

  13. Iodine Supplementation in Pregnancy and the Dilemma of Ambiguous Recommendations

    PubMed Central

    Andersen, Stine Linding; Laurberg, Peter

    2016-01-01

    Iodine requirements are increased during pregnancy, predominantly caused by an increase in renal iodide clearance and in the use of iodine for thyroid hormone production. Because iodine deficiency (ID) in pregnancy may be associated with neurodevelopmental deficits in the offspring, a pertinent question is at what level of iodine intake pregnant women should be advised to take iodine-containing supplements. The consensus reached by the WHO/UNICEF/ICCIDD in 2007 was that pregnant women should not be recommended to take iodine-containing supplements if the population in general had been iodine sufficient for at least 2 years. However, guidance on this differs between scientific societies. This review discusses iodine supplementation in pregnancy. Based on current evidence, the recommendations given by WHO/UNICEF/ICCIDD in 2007 provide a valid guidance on the use of iodine supplements in pregnant women. Women living in a population with a median urinary iodine concentration (UIC) at or above 100 µg/l are not in need of iodine supplementation in pregnancy. On the other hand, if the population median UIC is below 100 µg/l, pregnant women should take iodine-containing supplements until the population in general has been iodine sufficient for at least 2 years by way of universal salt iodization. PMID:27099837

  14. Iodine Supplementation in Pregnancy and the Dilemma of Ambiguous Recommendations.

    PubMed

    Andersen, Stine Linding; Laurberg, Peter

    2016-03-01

    Iodine requirements are increased during pregnancy, predominantly caused by an increase in renal iodide clearance and in the use of iodine for thyroid hormone production. Because iodine deficiency (ID) in pregnancy may be associated with neurodevelopmental deficits in the offspring, a pertinent question is at what level of iodine intake pregnant women should be advised to take iodine-containing supplements. The consensus reached by the WHO/UNICEF/ICCIDD in 2007 was that pregnant women should not be recommended to take iodine-containing supplements if the population in general had been iodine sufficient for at least 2 years. However, guidance on this differs between scientific societies. This review discusses iodine supplementation in pregnancy. Based on current evidence, the recommendations given by WHO/UNICEF/ICCIDD in 2007 provide a valid guidance on the use of iodine supplements in pregnant women. Women living in a population with a median urinary iodine concentration (UIC) at or above 100 µg/l are not in need of iodine supplementation in pregnancy. On the other hand, if the population median UIC is below 100 µg/l, pregnant women should take iodine-containing supplements until the population in general has been iodine sufficient for at least 2 years by way of universal salt iodization. PMID:27099837

  15. Early iron-deficiency-induced transcriptional changes in Arabidopsis roots as revealed by microarray analyses

    PubMed Central

    Buckhout, Thomas J; Yang, Thomas JW; Schmidt, Wolfgang

    2009-01-01

    Background Iron (Fe) is an essential nutrient in plants and animals, and Fe deficiency results in decreased vitality and performance. Due to limited bio-availability of Fe, plants have evolved sophisticated adaptive alterations in development, biochemistry and metabolism that are mainly regulated at the transcriptional level. We have investigated the early transcriptional response to Fe deficiency in roots of the model plant Arabidopsis, using a hydroponic system that permitted removal of Fe from the nutrient solution within seconds and transferring large numbers of plants with little or no mechanical damage to the root systems. We feel that this experimental approach offers significant advantages over previous and recent DNA microarray investigations of the Fe-deficiency response by increasing the resolution of the temporal response and by decreasing non-Fe deficiency-induced transcriptional changes, which are common in microarray analyses. Results The expression of sixty genes were changed after 6 h of Fe deficiency and 65% of these were found to overlap with a group of seventy-nine genes that were altered after 24 h. A disproportionally high number of transcripts encoding ion transport proteins were found, which function to increase the Fe concentration and decrease the zinc (Zn) concentration in the cytosol. Analysis of global changes in gene expression revealed that changes in Fe availability were associated with the differential expression of genes that encode transporters with presumed function in uptake and distribution of transition metals other than Fe. It appeared that under conditions of Fe deficiency, the capacity for Zn uptake increased, most probably the result of low specificity of the Fe transporter IRT1 that was induced upon Fe deficiency. The transcriptional regulation of several Zn transports under Fe deficiency led presumably to the homeostatic regulation of the cytosolic concentration of Zn and of other transition metal ions such as Mn to

  16. Stereocontrolled synthesis of rosuvastatin calcium via iodine chloride-induced intramolecular cyclization.

    PubMed

    Xiong, Fangjun; Wang, Haifeng; Yan, Lingjie; Han, Sheng; Tao, Yuan; Wu, Yan; Chen, Fener

    2016-01-28

    A novel, stereoselective approach towards rosuvastatin calcium from the known (S)-homoallylic alcohol has been developed. The synthesis is highlighted by a regio- and stereocontrolled ICl-induced intramolecular cyclization of chiral homoallylic carbonate to deliver the C6-formyl statin side chain with a syn-1,3-diol moiety. An improved synthesis of the rosuvastatin pyrimidine core moiety is also included. Moreover, this methodology is useful in the asymmetric synthesis of structural variants of statins such as pitavastatin calcium and atorvastatin calcium and their related analogs.

  17. Caspase 1 deficiency reduces inflammation-induced brain transcription

    PubMed Central

    Mastronardi, Claudio; Whelan, Fiona; Yildiz, Ozlem A.; Hannestad, Jonas; Elashoff, David; McCann, Samuel M.; Licinio, Julio; Wong, Ma-Li

    2007-01-01

    The systemic inflammatory response syndrome (SIRS) is a life-threatening medical condition characterized by a severe and generalized inflammatory state that can lead to multiple organ failure and shock. The CNS regulates many features of SIRS such as fever, cardiovascular, and neuroendocrine responses. Central and systemic manifestations of SIRS can be induced by LPS or IL-1β administration. The crucial role of IL-1β in inflammation has been further highlighted by studies of mice lacking caspase 1 (casp1, also known as IL-1β convertase), a protease that cleaves pro-IL-1β into mature IL-1β. Indeed, casp1 knockout (casp1−/−) mice survive lethal doses of LPS. The key role of IL-1β in sickness behavior and its de novo expression in the CNS during inflammation led us to test the hypothesis that IL-1β plays a major role modulating the brain transcriptome during SIRS. We show a gene–environment effect caused by LPS administration in casp1−/− mice. During SIRS, the expression of several genes, such as chemokines, GTPases, the metalloprotease ADAMTS1, IL-1RA, the inducible nitric oxide synthase, and cyclooxygenase-2, was differentially increased in casp1−/− mice. Our findings may contribute to the understanding of the molecular changes that take place within the CNS during sepsis and SIRS and the development of new therapies for these serious conditions. Our results indicate that those genes may also play a role in several neuropsychiatric conditions in which inflammation has been implicated and indicate that casp1 might be a potential therapeutic target for such disorders. PMID:17409187

  18. KLHDC10 Deficiency Protects Mice against TNFα-Induced Systemic Inflammation

    PubMed Central

    Yamaguchi, Namiko; Sekine, Shiori; Naguro, Isao; Sekine, Yusuke; Ichijo, Hidenori

    2016-01-01

    Systemic inflammatory response syndrome (SIRS) is a form of fatal acute inflammation for which there is no effective treatment. Here, we revealed that the ablation of Kelch domain containing 10 (KLHDC10), which we had originally identified as an activator of Apoptosis Signal-regulating Kinase 1 (ASK1), protects mice against TNFα-induced SIRS. The disease development of SIRS is mainly divided into two stages. The early stage is characterized by TNFα-induced systemic necroptosis, a regulated form of necrosis mediated by Receptor-interacting protein (RIP) 1/3 kinases. The later stage presents with an over-production of inflammatory cytokines induced by damage-associated molecular patterns (DAMPs), which are immunogenic cellular contents released from cells that underwent necroptosis. Analysis of TNFα-challenged mice revealed that KLHDC10-deficient mice show a reduction in the inflammatory response, but not in early systemic necroptosis. In vitro analysis suggested that the reduced inflammatory response observed in KLHDC10-deficient mice might be caused, in part, by enhanced necroptosis of inflammatory cells encountering DAMPs. Interestingly, the enhancement of necroptosis induced by KLHDC10 deficiency was selectively observed in inflammatory cells. Our results suggest that KLHDC10 is a cell-type specific regulator of necroptosis that ultimately contributes to the development of TNFα-induced SIRS. PMID:27631783

  19. A Polyamine-Deficient Diet Prevents Oxaliplatin-Induced Acute Cold and Mechanical Hypersensitivity in Rats

    PubMed Central

    Ferrier, Jérémy; Bayet-Robert, Mathilde; Pereira, Bruno; Daulhac, Laurence; Eschalier, Alain; Pezet, Denis; Moulinoux, Jacques-Philippe; Balayssac, David

    2013-01-01

    Background Oxaliplatin is an anticancer drug used for the treatment of advanced colorectal cancer, but it can also cause painful peripheral neuropathies. The pathophysiology of these neuropathies has not been yet fully elucidated, but may involve spinal N-methyl-D-aspartate (NMDA) receptors, particularly the NR2B subunit. As polyamines are positive modulators of NMDA-NR2B receptors and mainly originate from dietary intake, the modulation of polyamines intake could represent an interesting way to prevent/modulate neuropathic pain symptoms by opposing glutamate neurotransmission. Methods The effect of a polyamine deficient diet was investigated in an animal model of oxaliplatin-induced acute pain hypersensitivity using behavioral tests (mechanical and cold hypersensitivity). The involvement of spinal glutamate neurotransmission was monitored by using a proton nuclear magnetic resonance spectroscopy based metabolomic approach and by assessing the expression and phosphorylation of the NR2B subunit of the NMDA receptor. Results A 7-day polyamine deficient diet totally prevented oxaliplatin-induced acute cold hypersensitivity and mechanical allodynia. Oxaliplatin-induced pain hypersensitivity was not associated with an increase in NR2B subunit expression or phosphorylation, but with an increase of glutamate level in the spinal dorsal horn which was completely prevented by a polyamine deficient diet. As a validation that the oxaliplatin-induced hypersensitivity could be due to an increased activity of the spinal glutamate system, an intrathecal administration of the specific NR2B antagonist, ifenprodil, totally reversed oxaliplatin-induced mechanical and cold hypersensitivity. Conclusion A polyamine deficient diet could represent a promising and valuable nutritional therapy to prevent oxaliplatin-induced acute pain hypersensitivity. PMID:24204988

  20. Is Metformin-Induced Vitamin B12 Deficiency Responsible for Cognitive Decline in Type 2 Diabetes?

    PubMed Central

    Khattar, Deepti; Khaliq, Farah; Vaney, Neelam; Madhu, S. V.

    2016-01-01

    Introduction: Diabetes mellitus has its deleterious effects on various aspects of cognition such as memory function, executive function, and information-processing speed. The present study aims to assess cognition in diabetes patients and also tries to find its association with Vitamin B12 deficiency induced by metformin. Materials and Methods: Thirty diabetics taking metformin and thirty nondiabetic controls were enrolled. Event-related potentials (ERPs) and serum Vitamin B12 levels were evaluated in them. Results: Vitamin B12 levels were found to be deficient, and latencies of waves P200 and P300 were prolonged in the diabetics as compared to the controls. The dose and duration of metformin had no association with the ERPs. Conclusions: Although the Vitamin B12 levels were deficient in diabetics on metformin, this is not the reason behind the cognitive impairment found in them. PMID:27570337

  1. Exercise-induced cramp, myoglobinuria, and tubular aggregates in phosphoglycerate mutase deficiency.

    PubMed

    Oh, Shin J; Park, Kyung-Seok; Ryan, Hewitt F; Danon, Moris J; Lu, Jiesheng; Naini, Ali B; DiMauro, Salvatore

    2006-11-01

    We report two patients in whom phosphoglycerate mutase (PGAM) deficiency was associated with the triad of exercise-induced cramps, recurrent myoglobinuria, and tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels were elevated between attacks of myoglobinuria. Forearm ischemic exercise tests produced subnormal increases of venous lactate. Muscle biopsies showed subsarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM activities were markedly decreased (3% of the normal mean) and molecular genetic studies showed that both patients were homozygous for a described missense mutation (W78X). A review of 15 cases with tubular aggregates in the muscle biopsies from our laboratory and 15 cases with PGAM deficiency described in the literature showed that this clinicopathological triad is highly suggestive of PGAM deficiency. PMID:16881065

  2. Combined Tlr2 and Tlr4 Deficiency Increases Radiation-Induced Pulmonary Fibrosis in Mice

    SciTech Connect

    Paun, Alexandra; Fox, Jessica; Balloy, Viviane; Chignard, Michel; Qureshi, Salman T.; Haston, Christina K.

    2010-07-15

    Purpose: To determine whether Toll-like receptor 2 or 4 genotype alters the lung response to irradiation in C57BL/6 mice using a model developing a phenotype that resembles radiotherapy-induced fibrosis in both histological characteristics and onset post-treatment. Methods and Materials: The pulmonary phenotype of C57BL/6 mice deficient in each or both of these genes was assessed after an 18-Gy single dose to the thoracic cavity by survival time postirradiation, bronchoalveolar lavage cell differential, histological evidence of alveolitis and fibrosis, and gene expression levels, and compared with that of wild-type mice. Results: The lung phenotype of Tlr4-deficient and Tlr2-deficient mice did not differ from that of wild-type mice in terms of survival time postirradiation, or by histological evidence of alveolitis or fibrosis. In contrast, mice deficient in both receptors developed respiratory distress at an earlier time than did wild-type mice and presented an enhanced fibrotic response (13.5% vs. 5.8% of the lung by image analysis of histological sections, p < 0.001). No differences in bronchoalveolar cell differential counts, nor in numbers of apoptotic cells in the lung as detected through active caspase-3 staining, were evident among the irradiated mice grouped by Tlr genotype. Gene expression analysis of lung tissue revealed that Tlr2,4-deficient mice have increased levels of hyaluronidase 2 compared with both wild-type mice and mice lacking either Tlr2 or Tlr4. Conclusion: We conclude that a combined deficiency in both Tlr2 and Tlr4, but not Tlr2 or Tlr4 alone, leads to enhanced radiation-induced fibrosis in the C57BL/6 mouse model.

  3. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

    SciTech Connect

    Yasuda-Yamahara, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi; Koya, Daisuke; Haneda, Masakzu; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2015-09-18

    Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

  4. Planar Laser-Induced Iodine Fluorescence Measurements in Rarefied Hypersonic Flow

    NASA Technical Reports Server (NTRS)

    Cecil, Eric; McDaniel, James C.

    2005-01-01

    A planar laser-induced fluorescence (PLIF) technique is discussed and applied to measurement of time-averaged values of velocity and temperature in an I(sub 2)-seeded N(sub 2) hypersonic free jet facility. Using this technique, a low temperature, non-reacting, hypersonic flow over a simplified model of a reaction control system (RCS) was investigated. Data are presented of rarefied Mach 12 flow over a sharp leading edge flat plate at zero incidence, both with and without an interacting jet issuing from a nozzle built into the plate. The velocity profile in the boundary layer on the plate was resolved. The slip velocity along the plate, extrapolated from the velocity profile data, varied from nearly 100% down to 10% of the freestream value. These measurements are compared with results of a DSMC solution. The velocity variation along the centerline of a jet issuing from the plate was measured and found to match closely with the correlation of Ashkenas and Sherman. The velocity variation in the oblique shock terminating the jet was resolved sufficiently to measure the shock wave thickness.

  5. Deficiency in adiponectin exaggerates cigarette smoking exposure-induced cardiac contractile dysfunction: Role of autophagy.

    PubMed

    Hu, Nan; Yang, Lifang; Dong, Maolong; Ren, Jun; Zhang, Yingmei

    2015-10-01

    Second hand smoke is an independent risk factor for cardiovascular disease. Adiponectin (APN), an adipose-derived adipokine, has been shown to offer cardioprotective effect through an AMPK-dependent manner. This study was designed to evaluate the impact of adiponectin deficiency on second hand smoke-induced cardiac pathology and underlying mechanisms using a mouse model of side-stream smoke exposure. Adult wild-type (WT) and adiponectin knockout (APNKO) mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte function, and intracellular Ca2+ handling were evaluated. Autophagy and apoptosis were examined using western blot. 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) staining was used to evaluate reactive oxygen species (ROS) generation. Masson trichrome staining was employed to measure interstitial fibrosis. Our data revealed that adiponectin deficiency provoked smoke exposure-induced cardiomyopathy (compromised fractional shortening, disrupted cardiomyocyte function and intracellular Ca2+ homeostasis, apoptosis and ROS generation). In addition, these detrimental effects of side-stream smoke were accompanied by defective autophagolysosome formation, the effect of which was exacerbated by adiponectin deficiency. Blocking autophagolysosome formation using bafilomycin A1 (BafA1) negated the cardioprotective effect of rapamycin against smoke extract. Induction of autophagy using rapamycin and AMPKα activation using AICAR rescued against smoke extract-induced myopathic anomalies in APNKO mice. Our data suggest that adiponectin serves as an indispensable cardioprotective factor against side-stream smoke exposure-induced myopathic changes possibly through facilitating autophagolysosome formation. PMID:26276084

  6. Protease Activated Receptor-1 Deficiency Diminishes Bleomycin-Induced Skin Fibrosis

    PubMed Central

    Duitman, JanWillem; Ruela-de-Sousa, Roberta R; Shi, Kun; de Boer, Onno J; Borensztajn, Keren S; Florquin, Sandrine; Peppelenbosch, Maikel P; Spek, C Arnold

    2014-01-01

    Accumulating evidence shows that protease-activated receptor-1 (PAR-1) plays an important role in the development of fibrosis, including lung fibrosis. However, whether PAR-1 also plays a role in the development of skin fibrosis remains elusive. The aim of this study was to determine the role of PAR-1 in the development of skin fibrosis. To explore possible mechanisms by which PAR-1 could play a role, human dermal fibroblasts and keratinocytes were stimulated with specific PAR-1 agonists or antagonists. To investigate the role of PAR-1 in skin fibrosis, we subjected wild-type and PAR-1-deficient mice to a model of bleomycin-induced skin fibrosis. PAR-1 activation leads to increased proliferation and extra cellular matrix (ECM) production, but not migration of human dermal fibroblasts (HDF) in vitro. Moreover, transforming growth factor (TGF)-β production was increased in keratinocytes upon PAR-1 activation, but not in HDF. The loss of PAR-1 in vivo significantly attenuated bleomycin-induced skin fibrosis. The bleomycin-induced increase in dermal thickness and ECM production was reduced significantly in PAR-1-deficient mice compared with wild-type mice. Moreover, TGF-β expression and the number of proliferating fibroblasts were reduced in PAR-1-deficient mice although the difference did not reach statistical significance. This study demonstrates that PAR-1 contributes to the development of skin fibrosis and we suggest that PAR-1 potentiates the fibrotic response mainly by inducing fibroblast proliferation and ECM production. PMID:24842054

  7. Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

    PubMed

    Razvi, Shehla S; Richards, Jeremy B; Malik, Farhan; Cromar, Kevin R; Price, Roger E; Bell, Cynthia S; Weng, Tingting; Atkins, Constance L; Spencer, Chantal Y; Cockerill, Katherine J; Alexander, Amy L; Blackburn, Michael R; Alcorn, Joseph L; Haque, Ikram U; Johnston, Richard A

    2015-11-15

    Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology. PMID:26386120

  8. A quantitative model of the biogeochemical transport of iodine

    NASA Astrophysics Data System (ADS)

    Weng, H.; Ji, Z.; Weng, J.

    2010-12-01

    Iodine deficiency disorders (IDD) are among the world’s most prevalent public health problems yet preventable by dietary iodine supplements. To better understand the biogeochemical behavior of iodine and to explore safer and more efficient ways of iodine supplementation as alternatives to iodized salt, we studied the behavior of iodine as it is absorbed, accumulated and released by plants. Using Chinese cabbage as a model system and the 125I tracing technique, we established that plants uptake exogenous iodine from soil, most of which are transported to the stem and leaf tissue. The level of absorption of iodine by plants is dependent on the iodine concentration in soil, as well as the soil types that have different iodine-adsorption capacity. The leaching experiment showed that the remainder soil content of iodine after leaching is determined by the iodine-adsorption ability of the soil and the pH of the leaching solution, but not the volume of leaching solution. Iodine in soil and plants can also be released to the air via vaporization in a concentration-dependent manner. This study provides a scientific basis for developing new methods to prevent IDD through iodized vegetable production.

  9. [Overall child development: beyond pharmacological iodine supplementation].

    PubMed

    Gavilán, Enrique; Jiménez de Gracia, Laura

    2013-12-01

    Iodine deficiency is a factor that may compromise child development, but is not the only one. Other health determinants, some of them outside the healthcare system, are able to influence development. Fighting iodine deficiency may be a pragmatic and useful strategy if it is found to be not maleficent, beneficial to health, and cost-effective, and does not make us lose the notion that child development goes beyond psychomotor or cognitive performance. This article analyzes such constraints from a critical point of view. PMID:23916171

  10. [Overall child development: beyond pharmacological iodine supplementation].

    PubMed

    Gavilán, Enrique; Jiménez de Gracia, Laura

    2013-12-01

    Iodine deficiency is a factor that may compromise child development, but is not the only one. Other health determinants, some of them outside the healthcare system, are able to influence development. Fighting iodine deficiency may be a pragmatic and useful strategy if it is found to be not maleficent, beneficial to health, and cost-effective, and does not make us lose the notion that child development goes beyond psychomotor or cognitive performance. This article analyzes such constraints from a critical point of view.

  11. M1 Muscarinic Receptor Deficiency Attenuates Azoxymethane-Induced Chronic Liver Injury in Mice

    PubMed Central

    Rachakonda, Vikrant; Jadeja, Ravirajsinh N.; Urrunaga, Nathalie H.; Shah, Nirish; Ahmad, Daniel; Cheng, Kunrong; Twaddell, William S.; Raufman, Jean-Pierre; Khurana, Sandeep

    2015-01-01

    Cholinergic nervous system regulates liver injury. However, the role of M1 muscarinic receptors (M1R) in modulating chronic liver injury is uncertain. To address this gap in knowledge we treated M1R-deficient and WT mice with azoxymethane (AOM) for six weeks and assessed liver injury responses 14 weeks after the last dose of AOM. Compared to AOM-treated WT mice, M1R-deficient mice had attenuated liver nodularity, fibrosis and ductular proliferation, α-SMA staining, and expression of α1 collagen, Tgfβ-R, Pdgf-R, Mmp-2, Timp-1 and Timp-2. In hepatocytes, these findings were associated with reductions of cleaved caspase-3 staining and Tnf-α expression. In response to AOM treatment, M1R-deficient mice mounted a vigorous anti-oxidant response by upregulating Gclc and Nqo1 expression, and attenuating peroxynitrite generation. M1R-deficient mouse livers had increased expression of Trail-R2, a promotor of stellate cell apoptosis; dual staining for TUNNEL and α-SMA revealed increased stellate cells apoptosis in livers from M1R-deficient mice compared to those from WT. Finally, pharmacological inhibition of M1R reduced H2O2-induced hepatocyte apoptosis in vitro. These results indicate that following liver injury, anti-oxidant response in M1R-deficient mice attenuates hepatocyte apoptosis and reduces stellate cell activation, thereby diminishing fibrosis. Therefore, targeting M1R expression and activation in chronic liver injury may provide therapeutic benefit. PMID:26374068

  12. Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus.

    PubMed

    Tran, Phu V; Kennedy, Bruce C; Lien, Yu-Chin; Simmons, Rebecca A; Georgieff, Michael K

    2015-02-15

    Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency.

  13. Effect of copper deficiency on cocaine-induced seizures in rats

    SciTech Connect

    Kishore, V. )

    1991-03-11

    The objective of the present study was to study the effects of nutritional copper (Cu) deficiency on cocaine-induced seizures in rats. Following results were obtained when cocaine was given to 10 each of Cu-deficient (CUD) and Cu-sufficient (CUS) rats after 45 days on respective diets. For CUD and CUS groups of rats, respectively, (a) incidence of seizures was 60% and 40%; (b) time of onset for seizures was 8.42 {plus minus} 0.72 and 7.63 {plus minus} 1.00; (c) seizure severity was 2.5 {plus minus} 0.75 and 1.1 {plus minus} 0.45; and (d) 24 h mortality was 40% and none. Thus, except for time of onset, all other parameters for cocaine-induced seizures were significantly higher in CUD rats. These results clearly demonstrate that Cu deficiency enhances seizure-inducing effects of cocaine in rats. It is likely that the enhancement observed is due to a decrease in the hepatic metabolism of cocaine in CUD rats. This possibility is currently being investigated.

  14. Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice.

    PubMed

    Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, C Arnold

    2016-01-01

    Endogenously administered activated protein C ameliorates diabetic nephropathy (DN) in a protease-activated receptor-1 (PAR-1)-dependent manner, suggesting that PAR-1 activation limits the progression of DN. Activation of PAR-1 in fibroblast-like cells, however, induces proliferation and extracellular matrix production, thereby driving fibrotic disease. Considering the key role of mesangial proliferation and extracellular matrix production during DN, PAR-1 may in fact potentiate diabetes-induced kidney injury. To determine the net effect of PAR-1 in DN, streptozotocin-induced DN was studied in wild type and PAR-1 deficient mice. Subsequent mechanistic insight was obtained by assessing profibrotic responses of mesangial and tubular epithelial cells in vitro, following PAR-1 stimulation and inhibition. Despite having similar glucose levels, PAR-1 deficient mice developed less kidney damage after induction of diabetes, as evidenced by diminished proteinuria, plasma cystatin C levels, expansion of the mesangial area, and tubular atrophy. In vitro, PAR-1 signaling in mesangial cells led to increased proliferation and expression of matrix proteins fibronectin and collagen IV. Conversely, a reduction in both proliferation and fibronectin deposition was observed in diabetic PAR-1 deficient mice. Overall, we show that PAR-1 plays an important role in the development of DN and PAR-1 might therefore be an attractive therapeutic target to pursue in DN. PMID:27618774

  15. Deficiency of adiponectin protects against ovariectomy-induced osteoporosis in mice.

    PubMed

    Wang, Fang; Wang, Pei-xia; Wu, Xiao-lin; Dang, Su-ying; Chen, Yan; Ni, Ying-yin; Gao, Li-hong; Lu, Shun-yuan; Kuang, Ying; Huang, Lei; Fei, Jian; Wang, Zhu-gang; Pang, Xiao-fen

    2013-01-01

    Adipokine adiponectin (APN) has been recently reported to play a role in regulating bone mineral density (BMD). To explore the mechanism by which APN affects BMD, we investigated BMD and biomechanical strength properties of the femur and vertebra in sham-operated (Sham) and ovariectomized (OVX) APN knockout (KO) mice as compared to their operated wild-type (WT) littermates. The results show that APN deficiency has no effect on BMD but induces increased ALP activity and osteoclast cell number. While OVX indeed leads to significant bone loss in both femora and vertebras of WT mice with comparable osteogenic activity and a significant increase in osteoclast cell number when compared to that of sham control. However, no differences in BMD, ALP activity and osteoclast cell number were found between Sham and OVX mice deficient for APN. Further studies using bone marrow derived mesenchymal stem cells (MSCs) demonstrate an enhanced osteogenic differentiation and extracellular matrix calcification in APN KO mice. The possible mechanism for APN deletion induced acceleration of osteogenesis could involve increased proliferation of MSCs and higher expression of Runx2 and Osterix genes. These findings indicate that APN deficiency can protect against OVX-induced osteoporosis in mice, suggesting a potential role of APN in regulating the balance of bone formation and bone resorption, especially in the development of post-menopausal osteoporosis. PMID:23844209

  16. Probucol-Induced α-Tocopherol Deficiency Protects Mice against Malaria Infection.

    PubMed

    Herbas, Maria Shirely; Shichiri, Mototada; Ishida, Noriko; Kume, Aiko; Hagihara, Yoshihisa; Yoshida, Yasukazu; Suzuki, Hiroshi

    2015-01-01

    The emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. Recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. However, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. Here, we report on a new strategy to potentially treat malaria by using probucol, a drug that can reduce the plasma α-tocopherol concentration. Probucol pre-treatment for 2 weeks and treatment throughout the infection rescued from death of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition, survival was extended when the treatment started immediately after parasite inoculation. The ratio of lipid peroxidation products to parent lipids increased in plasma after 2 weeks treatment of probucol. This indicates that the protective effect of probucol might be mediated by the oxidative stressful environment induced by α-tocopherol deficiency. Probucol in combination with dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results indicated that probucol might be a candidate for a drug against malaria infection by inducing α-tocopherol deficiency without dietary α-tocopherol restriction. PMID:26296197

  17. Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice

    PubMed Central

    Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, C. Arnold

    2016-01-01

    Endogenously administered activated protein C ameliorates diabetic nephropathy (DN) in a protease-activated receptor-1 (PAR-1)-dependent manner, suggesting that PAR-1 activation limits the progression of DN. Activation of PAR-1 in fibroblast-like cells, however, induces proliferation and extracellular matrix production, thereby driving fibrotic disease. Considering the key role of mesangial proliferation and extracellular matrix production during DN, PAR-1 may in fact potentiate diabetes-induced kidney injury. To determine the net effect of PAR-1 in DN, streptozotocin-induced DN was studied in wild type and PAR-1 deficient mice. Subsequent mechanistic insight was obtained by assessing profibrotic responses of mesangial and tubular epithelial cells in vitro, following PAR-1 stimulation and inhibition. Despite having similar glucose levels, PAR-1 deficient mice developed less kidney damage after induction of diabetes, as evidenced by diminished proteinuria, plasma cystatin C levels, expansion of the mesangial area, and tubular atrophy. In vitro, PAR-1 signaling in mesangial cells led to increased proliferation and expression of matrix proteins fibronectin and collagen IV. Conversely, a reduction in both proliferation and fibronectin deposition was observed in diabetic PAR-1 deficient mice. Overall, we show that PAR-1 plays an important role in the development of DN and PAR-1 might therefore be an attractive therapeutic target to pursue in DN. PMID:27618774

  18. Involvement of oxidative stress in hydroquinone-induced cytotoxicity in catalase-deficient Escherichia coli mutants.

    PubMed

    Horita, Masako; Wang, Da-Hong; Tsutsui, Ken; Sano, Kuniaki; Masuoka, Noriyoshi; Kira, Shohei

    2005-10-01

    Hydroquinone is a benzene-derived metabolite. To clarify whether the reactive oxygen species (ROS) are involved in hydroquinone-induced cytotoxicity, we constructed transformants of Escherichia coli (E. coli) strains that express mammalian catalase gene derived from catalase mutant mice (Cs(b), Cs(c)) and the wild-type (Cs(a)) using a catalase-deficient E. coli UM255 as a recipient. Specific catalase activities of these tester strains were in order of Cs(a) > Cs(c) > Cs(b) > UM255, and their susceptibility to hydrogen peroxide (H2O2) showed UM255 > Cs(b) > Cs(c) > Cs(a). We found that hydroquinone exposure reduced the survival of catalase-deficient E. coli mutants in a dose-dependent manner significantly, especially in the strains with lower catalase activities. Hydroquinone toxicity was also confirmed using zone of inhibition test, in which UM255 was the most susceptible, showing the largest zone of growth inhibition, followed by Cs(b), Cs(c) and Cs(a). Furthermore, we found that hydroquinone-induced cell damage was inhibited by the pretreatment of catalase, ascorbic acid, dimethyl sulfoxide (DMSO), and ethylenediaminetetraacetic acid (EDTA), and augmented by superoxide dismutase (both CuZnSOD and MnSOD). The present results suggest that H2O2 is probably involved in hydroquinone-induced cytotoxicity in catalase-deficient E. coli mutants and catalase plays an important role in protection of the cells against hydroquinone toxicity.

  19. Probucol-Induced α-Tocopherol Deficiency Protects Mice against Malaria Infection

    PubMed Central

    Ishida, Noriko; Kume, Aiko; Hagihara, Yoshihisa; Yoshida, Yasukazu; Suzuki, Hiroshi

    2015-01-01

    The emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. Recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. However, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. Here, we report on a new strategy to potentially treat malaria by using probucol, a drug that can reduce the plasma α-tocopherol concentration. Probucol pre-treatment for 2 weeks and treatment throughout the infection rescued from death of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition, survival was extended when the treatment started immediately after parasite inoculation. The ratio of lipid peroxidation products to parent lipids increased in plasma after 2 weeks treatment of probucol. This indicates that the protective effect of probucol might be mediated by the oxidative stressful environment induced by α-tocopherol deficiency. Probucol in combination with dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results indicated that probucol might be a candidate for a drug against malaria infection by inducing α-tocopherol deficiency without dietary α-tocopherol restriction. PMID:26296197

  20. [Correction of isoproterenol-induced myocardial injury with magnesium salts in magnesium-deficient rats].

    PubMed

    Kharitonova, M V; Zheltova, A A; Spasov, A A; Smirnov, A V; Pan'shin, N G; Iezhitsa, I N

    2013-01-01

    The effect of Mg L-asparaginate (Mg-L-Asp), Mg chloride (MgCl2) and Mg sulfate (MgSO4) on the severity of isoproterenol-induced myocardial injury in Mg-deficient rats has been evaluated. To induce Mg deficiency, twenty-eight rats were placed on a low Mg diet (Mg content < 15 mg/kg) and demineralized water for 10 weeks. Twelve control rats were fed a basal control diet (Mg content = 500 mg/kg) and water (with Mg content 20 mg/l) for equal duration. On day 49 of low Mg diet, Mg-deficient rats were randomly divided into four groups: 1) group that continued to receive low Mg diet; 2) low Mg diet plus oral MgSO4; 3) low Mg diet plus oral Mg-L-Asp and 4) low Mg diet plus oral MgCl2 (50 mg of Mg per kg of body weight). Isoproterenol was injected subcutaneously (30 mg/kg BW, twice, at an interval of 24 hours) on the day 70 of the study, when plasma and erythrocyte Mg level in rats fed a low Mg diet were significantly decreased by 47% and 45% compared to intact animals. Twenty-four hours after second injection of isoproterenol, tests for activities of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were run and histopathological study was carried out. Administration of isoproterenol to rats resulted in significantly elevated plasma CK, LDH and AST, however analyses in Mg deficient group demonstrated more dramatically increased activity of CK and AST compared to control rats (3,06 and 4,67 fold in Mg-deficient group vs. 1,91 and 3,92 fold in intact group). Increased leakage of cardiac injury markers was concomitant to increased volume of fuchsinophilic cardiomyocytes (54.2 +/- 1.7% in Mg-deficient group and 38.9 +/- 1.9% in intact group, p < 0.05). However, pretreatment with of MgCl2, MgSO4 and Mg-L-Asp during 21 days favorably decreased sensitivity of myocardium to isoproterenol-induced ischemic injury. All evaluated salts significantly decreased myocyte marker enzymes as well as protected myocardium against isoproterenol-induced

  1. Iodine and Pregnancy

    PubMed Central

    Yarrington, Christina; Pearce, Elizabeth N.

    2011-01-01

    Iodine is a necessary element for the production of thyroid hormone. We will review the impact of dietary iodine status on thyroid function in pregnancy. We will discuss iodine metabolism, homeostasis, and nutritional recommendations for pregnancy. We will also discuss the possible effects of environmental contaminants on iodine utilization in pregnant women. PMID:21765996

  2. Evaluation of Accessibility of Iodinated Salt and Nutritional Iodine Status during Pregnancy

    PubMed Central

    Rostami, R; Beiranvand, A; Khakhali, HR; Salary, S; Aghasi, MR; Nourooz-Zadeh, J

    2012-01-01

    Background: To assess accessibility of iodinated salt and urinary iodine concentrations (UIC) during pregnancy. This cross-sectional study was carried out between October and December, 2009 in Urmia County, West Azerbaijan (WA), Iran. Methods: Data on demographic characteristics and iodinated salt accessibility were gathered through a questionnaire at 1st trimester. Household salt samples and urine samples (1st –and 3rd trimesters) were analyzed for iodine content. Pregnant women (n=490) at 1st trimester were interviewed. Of these, 490 subjects (12 prenatal care centers) were enrolled. Results: All participants declared that they were exclusive users of iodinated salt. Segregation of the household salt samples according to iodine content (0, 8, 15 and 30 ppm) revealed that the respective distributions were 3.3%, 1.4%, 23.7% and 71.6%. Median UIC levels at 1st and 3rd trimesters were 73.5 μg/L and 114μg/L respectively. Accordingly, 86% and 70% of participants exhibited UIC < 150 μg/L. Conclusion: Median UIC during pregnancy in WA is markedly lower than those previously reported for regions with adequate iodine status in the country. Thus, extra iodine is needed to maintain adequate iodine store during gestation. In addition, this preliminary study reveals that a significant proportion (28%) of the household salt samples had low iodine content (≤ 15 ppm) although a level (>20 and <40 ppm) is mandatory in Iran. Further studies are deemed necessary to elucidate the cause(s) for manifestation iodine deficiency among pregnant women despite 20 years after iodine fortification strategy. PMID:23113225

  3. Iodine volatility. [PWR; BWR

    SciTech Connect

    Beahm, E.C.; Shockley, W.E.

    1984-01-01

    The ultimate aim of this program is to couple experimental aqueous iodine volatilities to a fission product release model. Iodine partition coefficients, for inorganic iodine, have been measured during hydrolysis and radiolysis. The hydrolysis experiments have illustrated the importance of reaction time on iodine volatility. However, radiolysis effects can override hydrolysis in determining iodine volatility. In addition, silver metal in radiolysis samples can react to form silver iodide accompanied by a decrease in iodine volatility. Experimental data are now being coupled to an iodine transport and release model that was developed in the Federal Republic of Germany.

  4. The Impact of Carrot Enriched in Iodine through Soil Fertilization on Iodine Concentration and Selected Biochemical Parameters in Wistar Rats.

    PubMed

    Piątkowska, Ewa; Kopeć, Aneta; Bieżanowska-Kopeć, Renata; Pysz, Mirosław; Kapusta-Duch, Joanna; Koronowicz, Aneta Agnieszka; Smoleń, Sylwester; Skoczylas, Łukasz; Ledwożyw-Smoleń, Iwona; Rakoczy, Roksana; Maślak, Edyta

    2016-01-01

    Iodine is one of the trace elements which are essential for mammalian life. The major objective of iodine biofortification of plants is to obtain food rich in this trace element, which may increase its consumption by various populations. Additionally, it may reduce the risk of iodine deficiency diseases. In this research for the first time we have assessed the bioavailability of iodine from raw or cooked carrot biofortified with this trace element on iodine concentration in selected tissues and various biochemical parameters as well as mRNA expression of some genes involved in iodine metabolism in Wistar rats. Statistically, a significantly higher iodine level was determined in urine, faeces and selected tissues of rats fed a diet containing biofortified raw carrot as compared to a diet without iodine and a diet containing control cooked carrot. Biofortified raw carrot significantly increased triiodothyronine concentration as compared to animals from other experimental groups. The highest thyroid stimulating hormone level was determined in rats fed control cooked carrots. mRNA expression of selected genes was affected by different dietary treatment in rats' hearts. Biofortified raw and cooked carrot could be taken into account as a potential source of iodine in daily diets to prevent iodine deficiency in various populations. PMID:27043135

  5. The Impact of Carrot Enriched in Iodine through Soil Fertilization on Iodine Concentration and Selected Biochemical Parameters in Wistar Rats

    PubMed Central

    Piątkowska, Ewa; Kopeć, Aneta; Bieżanowska-Kopeć, Renata; Pysz, Mirosław; Kapusta-Duch, Joanna; Koronowicz, Aneta Agnieszka; Smoleń, Sylwester; Skoczylas, Łukasz; Ledwożyw-Smoleń, Iwona; Rakoczy, Roksana; Maślak, Edyta

    2016-01-01

    Iodine is one of the trace elements which are essential for mammalian life. The major objective of iodine biofortification of plants is to obtain food rich in this trace element, which may increase its consumption by various populations. Additionally, it may reduce the risk of iodine deficiency diseases. In this research for the first time we have assessed the bioavailability of iodine from raw or cooked carrot biofortified with this trace element on iodine concentration in selected tissues and various biochemical parameters as well as mRNA expression of some genes involved in iodine metabolism in Wistar rats. Statistically, a significantly higher iodine level was determined in urine, faeces and selected tissues of rats fed a diet containing biofortified raw carrot as compared to a diet without iodine and a diet containing control cooked carrot. Biofortified raw carrot significantly increased triiodothyronine concentration as compared to animals from other experimental groups. The highest thyroid stimulating hormone level was determined in rats fed control cooked carrots. mRNA expression of selected genes was affected by different dietary treatment in rats’ hearts. Biofortified raw and cooked carrot could be taken into account as a potential source of iodine in daily diets to prevent iodine deficiency in various populations. PMID:27043135

  6. The Impact of Carrot Enriched in Iodine through Soil Fertilization on Iodine Concentration and Selected Biochemical Parameters in Wistar Rats.

    PubMed

    Piątkowska, Ewa; Kopeć, Aneta; Bieżanowska-Kopeć, Renata; Pysz, Mirosław; Kapusta-Duch, Joanna; Koronowicz, Aneta Agnieszka; Smoleń, Sylwester; Skoczylas, Łukasz; Ledwożyw-Smoleń, Iwona; Rakoczy, Roksana; Maślak, Edyta

    2016-01-01

    Iodine is one of the trace elements which are essential for mammalian life. The major objective of iodine biofortification of plants is to obtain food rich in this trace element, which may increase its consumption by various populations. Additionally, it may reduce the risk of iodine deficiency diseases. In this research for the first time we have assessed the bioavailability of iodine from raw or cooked carrot biofortified with this trace element on iodine concentration in selected tissues and various biochemical parameters as well as mRNA expression of some genes involved in iodine metabolism in Wistar rats. Statistically, a significantly higher iodine level was determined in urine, faeces and selected tissues of rats fed a diet containing biofortified raw carrot as compared to a diet without iodine and a diet containing control cooked carrot. Biofortified raw carrot significantly increased triiodothyronine concentration as compared to animals from other experimental groups. The highest thyroid stimulating hormone level was determined in rats fed control cooked carrots. mRNA expression of selected genes was affected by different dietary treatment in rats' hearts. Biofortified raw and cooked carrot could be taken into account as a potential source of iodine in daily diets to prevent iodine deficiency in various populations.

  7. Genotypic variability within Tunisian grapevine varieties (Vitis vinifera L.) facing bicarbonate-induced iron deficiency.

    PubMed

    Ksouri, Riadh; Debez, Ahmed; Mahmoudi, Henda; Ouerghi, Zeineb; Gharsalli, Mohamed; Lachaâl, Mokhtar

    2007-05-01

    Morpho-physiological responses to bicarbonate-induced Fe deficiency were investigated in five Vitis vinifera L. Tunisian varieties (Khamri, Blanc3, Arich Dressé, Beldi, and Balta4). One-month-old woody cuttings were cultivated for 85days on a free calcareous soil irrigated with tap water containing increasing bicarbonate levels (0, 4, 8, 12, and 16mM NaHCO(3)). After this screening, a second experiment compared root biochemical responses of two contrasting genotypes (tolerant-sensitive) dealing with bicarbonate-induced iron deprivation (20microM Fe+/-10mM HCO(3)(-)) for 75days. Using morpho-physiological criteria, grapevine tolerance to HCO(3)(-)-induced Fe shortage appeared to be genotype-dependent: Balta4 and Beldi varieties showed the highest leaf-chlorosis score (especially at the extreme HCO(3)(-) levels), in contrast to Khamri variety. Growth parameters (shoot height, total leaf area, leaf number, and biomass production) as well as juvenile leaf chlorophyll content were also differently affected depending on both genotype and bicarbonate dose. At 16mM HCO(3)(-), Khamri was the less sensitive variety, contrasting with Balta4. On the other hand, chlorophyll content correlated positively with HCl-extractible Fe content of the juvenile leaves, suggesting that the grapevine response to iron deficiency may partly depend on to the plant ability to adequately supply young leaves with this element. Root biochemical responses revealed a relatively higher root acidification capacity in Khamri (tolerant) under Fe-deficiency while no significant changes occurred in Balta4 (sensitive). In addition, Fe(III)-reductase and phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) activities were strongly stimulated by Fe-deficiency in Khamri, while remaining constant in Balta4. These findings suggest that biochemical parameters may constitute reliable criteria for the selection of tolerant grapevine genotypes to iron chlorosis. PMID:17468003

  8. A New Fungal Diterpene Induces VDAC1-dependent Apoptosis in Bax/Bak-deficient Cells.

    PubMed

    Huang, Li; Han, Junjie; Ben-Hail, Danya; He, Luwei; Li, Baowei; Chen, Ziheng; Wang, Yueying; Yang, Yanlei; Liu, Lei; Zhu, Yushan; Shoshan-Barmatz, Varda; Liu, Hongwei; Chen, Quan

    2015-09-25

    The pro-apoptotic Bax and Bak proteins are considered central to apoptosis, yet apoptosis occurs in their absence. Here, we asked whether the mitochondrial protein VDAC1 mediates apoptosis independently of Bax/Bak. Upon screening a fungal secondary metabolite library for compounds inducing apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts, we identified cyathin-R, a new cyathane diterpenoid compound able to activate apoptosis in the absence of Bax/Bak via promotion of the VDAC1 oligomerization that mediates cytochrome c release. Diphenylamine-2-carboxilic acid, an inhibitor of VDAC1 conductance and oligomerization, inhibited cyathin-R-induced VDAC1 oligomerization and apoptosis. Similarly, Bcl-2 overexpression conferred resistance to cyathin-R-induced apoptosis and VDAC1 oligomerization. Silencing of VDAC1 expression prevented cyathin-R-induced apoptosis. Finally, cyathin-R effectively attenuated tumor growth and induced apoptosis in Bax/Bak-deficient cells implanted into a xenograft mouse model. Hence, this study identified a new compound promoting VDAC1-dependent apoptosis as a potential therapeutic option for cancerous cells lacking or presenting inactivated Bax/Bak.

  9. A New Fungal Diterpene Induces VDAC1-dependent Apoptosis in Bax/Bak-deficient Cells*

    PubMed Central

    Huang, Li; Han, Junjie; Ben-Hail, Danya; He, Luwei; Li, Baowei; Chen, Ziheng; Wang, Yueying; Yang, Yanlei; Liu, Lei; Zhu, Yushan; Shoshan-Barmatz, Varda; Liu, Hongwei; Chen, Quan

    2015-01-01

    The pro-apoptotic Bax and Bak proteins are considered central to apoptosis, yet apoptosis occurs in their absence. Here, we asked whether the mitochondrial protein VDAC1 mediates apoptosis independently of Bax/Bak. Upon screening a fungal secondary metabolite library for compounds inducing apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts, we identified cyathin-R, a new cyathane diterpenoid compound able to activate apoptosis in the absence of Bax/Bak via promotion of the VDAC1 oligomerization that mediates cytochrome c release. Diphenylamine-2-carboxilic acid, an inhibitor of VDAC1 conductance and oligomerization, inhibited cyathin-R-induced VDAC1 oligomerization and apoptosis. Similarly, Bcl-2 overexpression conferred resistance to cyathin-R-induced apoptosis and VDAC1 oligomerization. Silencing of VDAC1 expression prevented cyathin-R-induced apoptosis. Finally, cyathin-R effectively attenuated tumor growth and induced apoptosis in Bax/Bak-deficient cells implanted into a xenograft mouse model. Hence, this study identified a new compound promoting VDAC1-dependent apoptosis as a potential therapeutic option for cancerous cells lacking or presenting inactivated Bax/Bak. PMID:26253170

  10. Effect of expectoration on inflammation in induced sputum in alpha-1-antitrypsin deficiency.

    PubMed

    Gompertz, Simon; Hill, Adam T; Bayley, Darren L; Stockley, Robert A

    2006-06-01

    It is unclear how chronic expectoration influences airway inflammation in patients with chronic lung disease. The aim of this study was to investigate factors influencing inflammation in induced sputum samples, including, in particular, chronic sputum production. Myeloperoxidase, interleukin-8, leukotriene B4 (LTB4), neutrophil elastase, secretory leukoprotease inhibitor (SLPI) and protein leakage were compared in induced sputum samples from 48 patients (36 with chronic expectoration) with COPD (with and without alpha-1-antitrypsin deficiency; AATD), 9 individuals with AATD but without lung disease and 14 healthy controls. There were no differences in inflammation in induced sputum samples from healthy control subjects and from AATD deficient patients with normal lung function but without chronic expectoration (P>0.05). Inflammation in induced sputum from AATD patients with airflow obstruction and chronic sputum expectoration was significantly greater than for similar patients who did not expectorate: Interleukin-8 (P<0.01), elastase activity (P=0.01), and protein leakage (P<0.01). The presence of spontaneous sputum expectoration in AATD patients with airflow obstruction was associated with increased neutrophilic airway inflammation in induced sputum samples. The presence of chronic expectoration in some patients will clearly complicate interpretation of studies employing sputum induction where this feature has not been identified.

  11. The collision-induced non-adiabatic transitions from the f0 g+ state of the iodine ion-pair second tier

    NASA Astrophysics Data System (ADS)

    Akopyan, M. E.; Chinkova, I. Yu.; Fedorova, T. V.; Poretsky, S. A.; Pravilov, A. M.

    2004-07-01

    Non-adiabatic transitions from the f0 g+ state of the iodine ion-pair (IP) second tier induced by collision with iodine ground state molecules have been studied for the first time. The only I 2( f0g+,v f,J f limit→I2( X) F0u+,v F,J F) transition has been observed. No transitions between the states of the first and second tiers have been found. The dependences of the I 2( f0g+,v f,J f limit→I2( X) F0u+,v F,J F) transition rate constants on the vibrational vf=8-19, vF, rotational Jf≈55,85,105, JF quantum numbers, energy gaps, as well as their correlations with Franck-Condon factors (FCFs) of the initial and final levels have been studied. The principal features of the collision-induced non-adiabatic transitions in the first and second tiers are very similar.

  12. Zinc deficiency impairs neuronal precursor cell proliferation and induces apoptosis via p53-mediated mechanisms.

    PubMed

    Corniola, Rikki S; Tassabehji, Nadine M; Hare, Joan; Sharma, Girdhari; Levenson, Cathy W

    2008-10-27

    The potential importance of stem cells in the adult central nervous system (CNS) that cannot only divide, but also participate in neurogenesis, is now widely appreciated. While we know that the trace element zinc is needed for brain development, the role of this essential nutrient in adult stem cell proliferation and neurogenesis has not been investigated. Adult male rats fed a zinc-restricted diet had approximately 50% fewer Ki67-positive stem cells in the subgranular zone (SGZ) and granular cell layer of the dentate gyrus compared to both zinc-adequate and pair-fed controls (p<0.05). Zinc-deficient rats also had a significant increase the number of TUNEL-labeled cells in the SGZ compared to pair-fed rats (p<0.05). To explore the mechanisms responsible for the effects of zinc deficiency, cultured human Ntera-2 (NT2) neuronal precursor cells were deprived of zinc using the chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Consistent with the effects of deficiency in vivo, TPEN treatment resulted in a significant decrease in cellular proliferation, as measured by bromodeoxyuridine (BrdU) uptake, and an increase in caspase3/7-dependent apoptosis. These changes were accompanied by increases in nuclear p53. Oligonucleotide arrays, coupled with use of a dominant-negative p53 construct in NT2 cells, identified 14 differentially regulated p53 target genes. In the early phases zinc deficiency, p53 targets responsible for cell cycle arrest were induced. Continuation of deficiency resulted in the induction of a variety of pro-apoptotic genes such as transforming growth factor-beta (TGF-beta) and retinoblastoma-1 (Rb-1), as well as cellular protection genes such as glutathione peroxidase (GPx). These data suggest that zinc plays a role in neurogenesis by regulating p53-dependent molecular mechanisms that control neuronal precursor cell proliferation and survival.

  13. Vitamin A deficiency increases protein catabolism and induces urea cycle enzymes in rats.

    PubMed

    Esteban-Pretel, Guillermo; Marín, M Pilar; Cabezuelo, Francisco; Moreno, Verónica; Renau-Piqueras, Jaime; Timoneda, Joaquín; Barber, Teresa

    2010-04-01

    Chronic vitamin A deficiency induces a substantial delay in the rates of weight and height gain in both humans and experimental animals. This effect has been associated with an impaired nutrient metabolism and loss of body protein. Therefore, we analyzed the effect of vitamin A deficiency on endogenous proteolysis and nitrogen metabolism and its reversibility with all-trans retinoic acid (RA). Male weanling rats, housed in pairs, were pair-fed a vitamin A-deficient (VAD) or control diet until they were 60 d old. A group of deficient rats were further treated with daily intraperitoneal injections of all-trans RA for 10 d. Final body and tissue (i.e. liver and heart) weights were significantly lower and tissue:body weight ratios were similar in VAD rats and in controls. Conversely, the epididymal white fat:body weight ratio and the plasma concentrations of alanine aminotransferase and adiponectin were significantly higher in VAD rats, which also had hepatic macrovesicular lipid accumulations. Plasma and gastrocnemius muscle 3-methylhistidine, urine nitrogen, and plasma and urine urea concentrations were all significantly higher in the VAD group. The expression of the genes encoding urea cycle enzymes and their activities increased in VAD livers. These changes were partially reverted by all-trans RA. We propose that fuel partitioning in vitamin A deficiency may shift from fatty acids to protein catabolism as an energy source. Our results emphasize the importance of vitamin A on the energy balance control system and they provide an explanation for the role of vitamin A in protein turnover, development, and growth.

  14. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.

    PubMed

    Dubois, Vanessa; Laurent, Michaël R; Jardi, Ferran; Antonio, Leen; Lemaire, Katleen; Goyvaerts, Lotte; Deldicque, Louise; Carmeliet, Geert; Decallonne, Brigitte; Vanderschueren, Dirk; Claessens, Frank

    2016-02-01

    Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and β-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men.

  15. Low Iodine Content in the Diets of Hospitalized Preterm Infants

    PubMed Central

    Pearce, Elizabeth N.; Braverman, Lewis E.; He, Xuemei; Brown, Rosalind S.

    2012-01-01

    Context: Iodine is critical for normal thyroid hormone synthesis and brain development during infancy, and preterm infants are particularly vulnerable to the effects of both iodine deficiency and excess. Use of iodine-containing skin antiseptics in intensive care nurseries has declined substantially in recent years, but whether the current dietary iodine intake meets the requirement for hospitalized preterm infants is unknown. Objective: The aim of the study was to measure the iodine content of enteral and parenteral nutrition products commonly used for hospitalized preterm infants and estimate the daily iodine intake for a hypothetical 1-kg infant. Methods: We used mass spectrometry to measure the iodine concentration of seven preterm infant formulas, 10 samples of pooled donor human milk, two human milk fortifiers (HMF) and other enteral supplements, and a parenteral amino acid solution and soy-based lipid emulsion. We calculated the iodine provided by typical diets based on 150 ml/kg · d of formula, donor human milk with or without HMF, and parenteral nutrition. Results: Preterm formula provided 16.4–28.5 μg/d of iodine, whereas unfortified donor human milk provided only 5.0–17.6 μg/d. Adding two servings (six packets) of Similac HMF to human milk increased iodine intake by 11.7 μg/d, whereas adding two servings of Enfamil HMF increased iodine intake by only 0.9 μg/d. The other enteral supplements contained almost no iodine, nor did a parenteral nutrition-based diet. Conclusions: Typical enteral diets for hospitalized preterm infants, particularly those based on donor human milk, provide less than the recommended 30 μg/d of iodine, and parenteral nutrition provides almost no iodine. Additional iodine fortification should be considered. PMID:22337912

  16. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity

    PubMed Central

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian

    2015-01-01

    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity. PMID:26530337

  17. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity.

    PubMed

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian

    2015-01-01

    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

  18. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity.

    PubMed

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian

    2015-01-01

    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity. PMID:26530337

  19. Low molybdenum state induced by tungsten as a model of molybdenum deficiency in rats.

    PubMed

    Yoshida, Munehiro; Nakagawa, Mikihito; Hosomi, Ryota; Nishiyama, Toshimasa; Fukunaga, Kenji

    2015-05-01

    Organ molybdenum (Mo) concentration and the activity of hepatic sulfite oxidase and xanthine oxidase were compared in tungsten-administered rats as well as rats fed with a low Mo diet to evaluate the use of tungsten-administered rats as a model of Mo deficiency. Twenty-four male 6-week-old Wistar rats were divided into four groups according to diet (AIN93G diet (control diet) or the control diet minus ammonium molybdate (low Mo diet)) and drinking water (deionized water or deionized water containing 200 μg/mL tungsten in the form of sodium tungstate). Mo content in the control and low Mo diets were 196 and 42 ng/g, respectively. Intake of the low Mo diet significantly reduced the Mo content of several organs and serum. Decrease in hepatic sulfite oxidase activity was also induced by the low Mo diet. The administration of tungsten induced marked decreases in organ Mo content and the activity of hepatic sulfite oxidase and xanthine oxidase. These decreases induced by tungsten administration were more pronounced than those induced by just a low Mo diet. Serum uric acid was also reduced by tungsten administration irrespective of Mo intake. Although a comparatively high accumulation of tungsten (3 to 9 μg/g) was observed in the kidneys and liver, adverse effects of tungsten accumulation on liver and kidney function were not observed in serum biochemical tests. These results indicate that tungsten-administered animals may be used as a model of Mo deficiency.

  20. Urokinase plasminogen activator receptor-deficient mice demonstrate reduced hyperoxia-induced lung injury.

    PubMed

    van Zoelen, Marieke A D; Florquin, Sandrine; de Beer, Regina; Pater, Jennie M; Verstege, Marleen I; Meijers, Joost C M; van der Poll, Tom

    2009-06-01

    Patients with respiratory failure often require supplemental oxygen therapy and mechanical ventilation. Although both supportive measures are necessary to guarantee adequate oxygen uptake, they can also cause or worsen lung inflammation and injury. Hyperoxia-induced lung injury is characterized by neutrophil infiltration into the lungs. The urokinase plasminogen activator receptor (uPAR) has been deemed important for leukocyte trafficking. To determine the expression and function of neutrophil uPAR during hyperoxia-induced lung injury, uPAR expression was determined on pulmonary neutrophils of mice exposed to hyperoxia. Hyperoxia exposure (O2>80%) for 4 days elicited a pulmonary inflammatory response as reflected by a profound rise in the number of neutrophils that were recovered from bronchoalveolar lavage fluid and lung cell suspensions, as well as increased bronchoalveolar keratinocyte-derived chemokine, interleukin-6, total protein, and alkaline phosphatase levels. In addition, hyperoxia induced the migration of uPAR-positive granulocytes into lungs from wild-type mice compared with healthy control mice (exposed to room air). uPAR deficiency was associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, which was accompanied by a strong reduction in lung injury. Furthermore, in uPAR(-/-) mice, activation of coagulation was diminished. These data suggest that uPAR plays a detrimental role in hyperoxia-induced lung injury and that uPAR deficiency is associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, accompanied by decreased pulmonary injury. PMID:19435793

  1. Thrombospondin 1 Deficiency Ameliorates the Development of Adriamycin-Induced Proteinuric Kidney Disease

    PubMed Central

    Maimaitiyiming, Hasiyeti; Zhou, Qi; Wang, Shuxia

    2016-01-01

    Accumulating evidence suggests that thrombospondin 1 (TSP1) is an important player in diabetic nephropathy. However, the role of TSP1 in podocyte injury and the development of non-diabetic proteinuric kidney disease is largely unknown. In the current study, by using a well-established podocyte injury model (adriamycin-induced nephropathy mouse model), we examined the contribution of TSP1 to the development of proteinuric kidney disease. We found that TSP1 was up-regulated in the glomeruli, notably in podocytes, in adriamycin injected mice before the onset of proteinuria. ADR treatment also stimulated TSP1 expression in cultured human podocytes in vitro. Moreover, increased TSP1 mediated ADR-induced podocyte apoptosis and actin cytoskeleton disorganization. This TSP1’s effect was through a CD36-dependent mechanism and involved in the stimulation of p38MAPK pathway. Importantly, in vivo data demonstrated that TSP1 deficiency protected mice from ADR induced podocyte loss and foot process effacement. ADR induced proteinuria, glomerulosclerosis, renal macrophage infiltration and inflammation was also attenuated in TSP1 deficient mice. Taken together, these studies provide new evidence that TSP1 contributes to the development of non-diabetic proteinuric kidney disease by stimulating podocyte injury and the progression of renal inflammation. PMID:27196103

  2. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, C. K.; Mazumder, B.; Fox, P. L.

    2000-01-01

    A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these

  3. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency.

    PubMed

    Mukhopadhyay, C K; Mazumder, B; Fox, P L

    2000-07-14

    A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these

  4. CCR5 deficiency increased susceptibility to lipopolysaccharide-induced acute renal injury.

    PubMed

    Lee, Dong Hun; Park, Mi Hee; Hwang, Chul Ju; Hwang, Jae Yeon; Yoon, Hae Suk; Yoon, Do Young; Hong, Jin Tae

    2016-05-01

    C-C chemokine receptor 5 (CCR5) regulates leukocyte chemotaxis and activation, and its deficiency exacerbates development of nephritis. Therefore, we investigated the role of CCR5 during lipopolysaccharide (LPS)-induced acute kidney injury. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice, both aged about 10 months, had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg). Compared with CCR5+/+ mice, CCR5-/- mice showed increased mortality and renal injury, including elevated creatinine and blood urea nitrogen levels, following LPS challenge. Compared to CCR5+/+ mice, CCR5-/- mice also exhibited greater increases in the serum concentrations of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β following LPS challenge. Furthermore, infiltration of macrophages and neutrophils, expression of intracellular adhesion molecule (ICAM)-1, and the number of apoptotic cells were more greatly increased by LPS treatment in CCR5-/- mice than in CCR5+/+ mice. The concentrations of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β were also significantly increased in the kidney of CCR5-/- mice after LPS challenge. Moreover, primary kidney cells from CCR5-/- mice showed greater increases in TNF-α production and p38 MAP kinase activation following treatment with LPS compared with that observed in the cells from CCR5+/+ mice. LPS-induced TNF-α production and apoptosis in the primary kidney cells from CCR5-/- mice were inhibited by treatment with p38 MAP kinase inhibitor. These results suggest that CCR5 deficiency increased the production of TNF-α following LPS treatment through increased activation of the p38 pathway in the kidney, resulting in renal apoptosis and leukocyte infiltration and led to exacerbation of LPS-induced acute kidney injury.

  5. Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice.

    PubMed

    Yiannikouris, Frederique; Gupte, Manisha; Putnam, Kelly; Thatcher, Sean; Charnigo, Richard; Rateri, Debra L; Daugherty, Alan; Cassis, Lisa A

    2012-12-01

    Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in Agt(fl/fl) and adipocyte angiotensinogen-deficient mice (Agt(aP2)). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed Agt(fl/fl) compared with Agt(aP2) mice (124 ± 3 versus 128 ± 3 mm Hg, respectively). In Agt(fl/fl) mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134 ± 2 mm Hg; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit an increase in systolic blood pressure (126 ± 2 mm Hg). Plasma angiotensin II concentrations were increased by high-fat feeding in Agt(fl/fl) mice (low fat, 32 ± 14; high fat, 219 ± 58 pg/mL; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18 ± 7 pg/mL). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat- and high fat-fed Agt(aP2) mice compared with controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity hypertension.

  6. Nutritional status of iodine in pregnant women in Catalonia (Spain): study on hygiene-dietetic habits and iodine in urine

    PubMed Central

    2011-01-01

    Background It is a priority to achieve an adequate nutritional status of iodine during pregnancy since iodine deficiency in this population may have repercussions on the mother during both gestation and post partum as well as on the foetus, the neonate and the child at different ages. According to the WHO, iodine deficiency is the most frequent cause of mental retardation and irrreversible cerebral lesions around the world. However, few studies have been published on the nutritional status of iodine in the pregnant population within the Primary Care setting, a health care level which plays an essential role in the education and control of pregnant women. Therefore, the aim of the present study is: 1.- To know the hygiene-dietetic habits related to the intake of foods rich in iodine and smoking during pregnancy. 2.- To determine the prevalence of iodine deficiency and the factors associated with its appearance during pregnancy. Methods/design We will perform a cluster randomised, controlled, multicentre trial. Randomisation unit: Primary Care Team. Study population: 898 pregnant women over the age of 17 years attending consultation to a midwife during the first trimester of pregnancy in the participating primary care centres. Outcome measures: consumption of iodine-rich foods and iodine deficiency. Points of assessment: each trimester of the gestation. Intervention: group education during the first trimester of gestation on healthy hygiene-dietetic habits and the importance of an adequate iodine nutritional status. Statistical analysis: descriptive analysis of all variables will be performed as well as multilevel logistic regression. All analyses will be done carried out on an intention to treat basis and will be fitted for potential confounding factors and variables of clinical importance. Discussion Evidence of generalised iodine deficiency during pregnancy could lead to the promotion of interventions of prevention such as how to improve and intensify health care

  7. Iodine status in the Nordic countries – past and present

    PubMed Central

    Nyström, Helena Filipsson; Brantsæter, Anne Lise; Erlund, Iris; Gunnarsdottir, Ingibjörg; Hulthén, Lena; Laurberg, Peter; Mattisson, Irene; Rasmussen, Lone Banke; Virtanen, Suvi; Meltzer, Helle Margrete

    2016-01-01

    Background Adequate iodine nutrition is dependent on ground water content, seafood, and, as many countries use iodized cow fodder, dairy products. In most countries, salt fortification programs are needed to assure adequate iodine intake. Objectives The objectives are threefold: 1) to describe the past and present iodine situation in the Nordic countries, 2) to identify important gaps of knowledge, and 3) to highlight differences among the Nordic countries’ iodine biomonitoring and fortification policies. Design Historical data are compared with the current situation. The Nordic countries’ strategies to achieve recommended intake and urine iodine levels and their respective success rates are evaluated. Results In the past, the iodine situation ranged from excellent in Iceland to widespread goiter and cretinism in large areas of Sweden. The situation was less severe in Norway and Finland. According to a 1960 World Health Organization (WHO) report, there were then no observations of iodine deficiency in Denmark. In Sweden and Finland, the fortification of table salt was introduced 50–75 years ago, and in Norway and Finland, the fortification of cow fodder starting in the 1950s helped improve the population's iodine status due to the high intake of milk. In Denmark, iodine has been added to household salt and salt in bread for the past 15 years. The Nordic countries differ with regard to regulations and degree of governmental involvement. There are indications that pregnant and lactating women, the two most vulnerable groups, are mildly deficient in iodine in several of the Nordic countries. Conclusion The Nordic countries employ different strategies to attain adequate iodine nutrition. The situation is not optimal and is in need of re-evaluation. Iodine researchers, Nordic national food administrations, and Nordic governmental institutions would benefit from collaboration to attain a broader approach and guarantee good iodine health for all. PMID:27283870

  8. Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review.

    PubMed

    O'Rourke, Timothy K; Wosnitzer, Matthew S

    2016-10-01

    Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes. Few studies have systematically investigated hormonal changes induced by long-term opioid administration or the effects of testosterone replacement therapy (TRT) in patients with OPIAD. Clomiphene citrate, a selective estrogen receptor modulator (SERM), is a testosterone enhancement treatment which upregulates endogenous hypothalamic function. This review will focus on the pathophysiology, diagnosis, and management of OPIAD, including summary of literature evaluating OPIAD treatment with TRT, and areas of future investigation. PMID:27586511

  9. Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMV-induced meningitis.

    PubMed

    Mundt, Sarah; Engelhardt, Britta; Kirk, Christopher J; Groettrup, Marcus; Basler, Michael

    2016-01-01

    In addition to antigen processing, immunoproteasomes were recently shown to exert functions influencing cytokine production by monocytes and T cells, T-helper cell differentiation, and T-cell survival. Moreover, selective inhibition of the immunoproteasome subunit LMP7 ameliorated symptoms of autoimmune diseases including CD4(+) T-cell mediated EAE. In this study, we show that LMP7 also plays a crucial role in the pathogenesis of lymphocytic choriomeningitis virus (LCMV)-induced meningitis mediated by CTLs. Mice lacking functional LMP7 display delayed and reduced clinical signs of disease accompanied by a strongly decreased inflammatory infiltration into the brain. Interestingly, we found that selective inhibition and genetic deficiency of LMP7 affect the pathogenesis of LCMV-induced meningitis in a distinct manner. Our findings support the important role of LMP7 in inflammatory disorders and suggest immunoproteasome inhibition as a novel strategy against inflammation-induced neuropathology in the CNS. PMID:26464284

  10. Effect of chronic douching with polyvinylpyrrolidone-iodine on iodine absorption and thyroid function

    SciTech Connect

    Safran, M.; Braverman, L.E.

    1982-07-01

    Daily vaginal douching with polyvinylpyrrolidone-iodine in 12 euthyroid volunteers for 14 days resulted in a significant increase in serum total iodine concentration and urine iodine excretion. The increase in serum total iodine was associated with a marked decrease in 24-hour /sup 123/I uptake by the thyroid and a small but significant increase in serum thyrotropin (TSH) concentration. However, values for serum TSH never rose above the normal range. No significant changes in serum thyroxine (T4), free T4 index (FTI), or triiodothyronine concentrations were observed, although serum T4 and FTI did decrease slightly during treatment. The findings suggest that iodine is absorbed across the vaginal mucosa and that the subsequent increase in serum total iodine does induce subtle increases in serum TSH concentration. There was no evidence, however, of overt hypothyroidism in these euthyroid women.

  11. Costs and trade-offs of grazer-induced defenses in Scenedesmus under deficient resource

    PubMed Central

    Zhu, Xuexia; Wang, Jun; Chen, Qinwen; Chen, Ge; Huang, Yuan; Yang, Zhou

    2016-01-01

    The green alga Scenedesmus obliquus can form inducible defensive morphs under grazing threat. Costs and trade-offs of inducible defense are expected to accompany the benefits of defensive morphs, but are hard to detect under nutrient-sufficient experimental conditions. To test the existence of costs associated with inducible defense, we cultured S. obliquus along resource availability gradients in the presence or absence of infochemical cues from Daphnia, and measured the strength of defensive colony formation and fitness characters. Under the lowest phosphorous concentration, the expression of inducible defensive colony resulted in decreased growth rate, which provides direct evidence for physiological costs. Along the gradient reduction of phosphorous concentration or light intensity, inducible defense in S. obliquus showed a decreasing trend. However, the photosynthetic efficiency of S. obliquus was barely affected by its defense responses, suggesting that the negative correlations between resource availability and colony formation of this alga may be due to resource-based trade-offs in the allocation of limited resources. Thus, our results indicated that expression of inducible defense of S. obliquus was impaired under insufficient phosphorus or light. Furthermore, under severe phosphate deficiency, obvious physiological costs of inducible defense could be detected even though defensive colony formation also decreased significantly. PMID:26932369

  12. Myeloid Mineralocorticoid Receptor Deficiency Inhibits Aortic Constriction-Induced Cardiac Hypertrophy in Mice

    PubMed Central

    Zheng, Xiao Jun; Zhang, Wu Chang; Sun, Xue Nan; Yang, Qing Zhen; Ma, Shu Min; Huang, Baozhuan; Berger, Stefan; Wang, Wang; Wu, Yong; Yu, Ying; Duan, Sheng Zhong; Mortensen, Richard M.

    2014-01-01

    Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims to determine whether MR deficiency in myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid MR knockout (MMRKO) mice and littermate control mice were subjected to abdominal aortic constriction (AAC) or sham operation. We found that AAC-induced cardiac hypertrophy and fibrosis were significantly attenuated in MMRKO mice. Expression of genes important in generating reactive oxygen species was decreased in MMRKO mice, while that of manganese superoxide dismutase increased. Furthermore, expression of genes important in cardiac metabolism was increased in MMRKO hearts. Macrophage infiltration in the heart was inhibited and expression of inflammatory genes was decreased in MMRKO mice. In addition, aortic fibrosis and inflammation were attenuated in MMRKO mice. Taken together, our data indicated that MR deficiency in myeloid cells effectively attenuated aortic constriction-induced cardiac hypertrophy and fibrosis, as well as aortic fibrosis and inflammation. PMID:25354087

  13. ALDH2 Deficiency Promotes Ethanol-Induced Gut Barrier Dysfunction and Fatty Liver in Mice

    PubMed Central

    Chaudhry, Kamljit K.; Samak, Geetha; Shukla, Pradeep K.; Mir, Hina; Gangwar, Ruchika; Manda, Bhargavi; Isse, Toyohi; Kawamoto, Toshihiro; Salaspuro, Mikko; Kaihovaara, Pertti; Dietrich, Paula; Dragatsis, Ioannis; Nagy, Laura E.; Rao, RadhaKrishna

    2015-01-01

    Background Acetaldehyde, the toxic ethanol metabolite, disrupts intestinal epithelial barrier function. Aldehyde dehydrogenase (ALDH) detoxifies acetaldehyde into acetate. Sub populations of Asians and Native Americans show polymorphism with loss of function mutations in ALDH2. We evaluated the effect of ALDH2 deficiency on ethanol-induced disruption of intestinal epithelial tight junctions and adherens junctions, gut barrier dysfunction and liver injury. Methods Wild type and ALDH2 deficient mice were fed (1–6%) in Lieber-DeCarli diet for 4 weeks. Gut permeability in vivo measured by plasma-to-luminal flux of FITC-inulin, tight junction and adherens junction integrity analyzed by confocal microscopy and liver injury was assessed by analysis of plasma transaminase activity, histopathology and liver triglyceride. Results Ethanol feeding elevated colonic mucosal acetaldehyde, which was significantly greater in ALDH2 deficient mice. ALDH2−/− mice showed a drastic reduction in the ethanol diet intake. Therefore, this study was continued only in wild type and ALDH2+/− mice. Ethanol feeding elevated mucosal inulin permeability in distal colon, but not in proximal colon, ileum or jejunum of wild type mice. In ALDH2+/− mice, ethanol-induced inulin permeability in distal colon was not only higher than that in wild type mice, but inulin permeability was also elevated in the proximal colon, ileum and jejunum. Greater inulin permeability in distal colon of ALDH2+/− mice was associated with a more severe redistribution of tight junction and adherens junction proteins from the intercellular junctions. In ALDH2+/− mice, but not in wild type mice, ethanol feeding caused a loss of junctional distribution of tight junction and adherens junction proteins in the ileum. Histopathology, plasma transaminases and liver triglyceride analyses showed that ethanol-induced liver damage was significantly greater in ALDH2+/− mice compared to wild type mice. Conclusion These data

  14. Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance

    PubMed Central

    Xiong, Dingding; He, Huamei; James, Jeanne; Tokunaga, Chonan; Powers, Corey; Huang, Yan; Osinska, Hanna; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Balschi, James A.; Javadov, Sabzali; McGowan, Francis X.; Strauss, Arnold W.

    2013-01-01

    The very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first step of mitochondrial β-oxidation. Patients with VLCAD deficiency present with hypoketotic hypoglycemia and cardiomyopathy, which can be exacerbated by fasting and/or cold stress. Global VLCAD knockout mice recapitulate these phenotypes: mice develop cardiomyopathy, and cold exposure leads to rapid hypothermia and death. However, the contribution of different tissues to development of these phenotypes has not been studied. We generated cardiac-specific VLCAD-deficient (cVLCAD−/−) mice by Cre-mediated ablation of the VLCAD in cardiomyocytes. By 6 mo of age, cVLCAD−/− mice demonstrated increased end-diastolic and end-systolic left ventricular dimensions and decreased fractional shortening. Surprisingly, selective VLCAD gene ablation in cardiomyocytes was sufficient to evoke severe cold intolerance in mice who rapidly developed severe hypothermia, bradycardia, and markedly depressed cardiac function in response to fasting and cold exposure (+5°C). We conclude that cardiac-specific VLCAD deficiency is sufficient to induce cold intolerance and cardiomyopathy and is associated with reduced ATP production. These results provide strong evidence that fatty acid oxidation in myocardium is essential for maintaining normal cardiac function under these stress conditions. PMID:24285112

  15. Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance.

    PubMed

    Xiong, Dingding; He, Huamei; James, Jeanne; Tokunaga, Chonan; Powers, Corey; Huang, Yan; Osinska, Hanna; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Balschi, James A; Javadov, Sabzali; McGowan, Francis X; Strauss, Arnold W; Khuchua, Zaza

    2014-02-01

    The very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first step of mitochondrial β-oxidation. Patients with VLCAD deficiency present with hypoketotic hypoglycemia and cardiomyopathy, which can be exacerbated by fasting and/or cold stress. Global VLCAD knockout mice recapitulate these phenotypes: mice develop cardiomyopathy, and cold exposure leads to rapid hypothermia and death. However, the contribution of different tissues to development of these phenotypes has not been studied. We generated cardiac-specific VLCAD-deficient (cVLCAD(-/-)) mice by Cre-mediated ablation of the VLCAD in cardiomyocytes. By 6 mo of age, cVLCAD(-/-) mice demonstrated increased end-diastolic and end-systolic left ventricular dimensions and decreased fractional shortening. Surprisingly, selective VLCAD gene ablation in cardiomyocytes was sufficient to evoke severe cold intolerance in mice who rapidly developed severe hypothermia, bradycardia, and markedly depressed cardiac function in response to fasting and cold exposure (+5°C). We conclude that cardiac-specific VLCAD deficiency is sufficient to induce cold intolerance and cardiomyopathy and is associated with reduced ATP production. These results provide strong evidence that fatty acid oxidation in myocardium is essential for maintaining normal cardiac function under these stress conditions.

  16. Root antioxidant responses of two Pisum sativum cultivars to direct and induced Fe deficiency.

    PubMed

    Jelali, N; Donnini, S; Dell'Orto, M; Abdelly, C; Gharsalli, M; Zocchi, G

    2014-05-01

    The contribution of antioxidant defence systems in different tolerance to direct and bicarbonate-induced Fe deficiency was evaluated in two pea cultivars (Kelvedon, tolerant and Lincoln, susceptible). Fe deficiency enhanced lipid peroxidation and H2 O2 concentration in roots of both cultivars, particularly in the sensitive one grown under bicarbonate supply. The results obtained on antioxidant activities (SOD, CAT, POD) suggest that H2 O2 accumulation could be due to an overproduction of this ROS and, at the same time, to a poor capacity to detoxify it. Moreover, under bicarbonate supply the activity of POD isoforms was reduced only in the sensitive cultivar, while in the tolerant one a new isoform was detected, suggesting that POD activity might be an important contributor to pea tolerance to Fe deficiency. The presence of bicarbonate also resulted in stimulation of GR, MDHAR and DHAR activities, part of the ASC-GSH pathway, which was higher in the tolerant cultivar than in the sensitive one. Overall, while in the absence of Fe only slight differences were reported between the two cultivars, the adaptation of Kelvedon to the presence of bicarbonate seems to be related to its greater ability to enhance the antioxidant response at the root level.

  17. Nuclear Lamin A/C Deficiency Induces Defects in Cell Mechanics, Polarization, and Migration

    PubMed Central

    Lee, Jerry S. H.; Hale, Christopher M.; Panorchan, Porntula; Khatau, Shyam B.; George, Jerry P.; Tseng, Yiider; Stewart, Colin L.; Hodzic, Didier; Wirtz, Denis

    2007-01-01

    Lamin A/C is a major constituent of the nuclear lamina, a thin filamentous protein layer that lies beneath the nuclear envelope. Here we show that lamin A/C deficiency in mouse embryonic fibroblasts (Lmna−/− MEFs) diminishes the ability of these cells to polarize at the edge of a wound and significantly reduces cell migration speed into the wound. Moreover, lamin A/C deficiency induces significant separation of the microtubule organizing center (MTOC) from the nuclear envelope. Investigations using ballistic intracellular nanorheology reveal that lamin A/C deficiency also dramatically affects the micromechanical properties of the cytoplasm. Both the elasticity (stretchiness) and the viscosity (propensity of a material to flow) of the cytoplasm in Lmna−/− MEFs are significantly reduced. Disassembly of either the actin filament or microtubule networks in Lmna+/+ MEFs results in decrease of cytoplasmic elasticity and viscosity down to levels found in Lmna−/− MEFs. Together these results show that both the mechanical properties of the cytoskeleton and cytoskeleton-based processes, including cell motility, coupled MTOC and nucleus dynamics, and cell polarization, depend critically on the integrity of the nuclear lamina, which suggest the existence of a functional mechanical connection between the nucleus and the cytoskeleton. These results also suggest that cell polarization during cell migration requires tight mechanical coupling between MTOC and nucleus, which is mediated by lamin A/C. PMID:17631533

  18. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury.

    PubMed

    Martens, Lauren Herl; Zhang, Jiasheng; Barmada, Sami J; Zhou, Ping; Kamiya, Sherry; Sun, Binggui; Min, Sang-Won; Gan, Li; Finkbeiner, Steven; Huang, Eric J; Farese, Robert V

    2012-11-01

    Progranulin (PGRN) is a widely expressed secreted protein that is linked to inflammation. In humans, PGRN haploinsufficiency is a major inherited cause of frontotemporal dementia (FTD), but how PGRN deficiency causes neurodegeneration is unknown. Here we show that loss of PGRN results in increased neuron loss in response to injury in the CNS. When exposed acutely to 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydrophine (MPTP), mice lacking PGRN (Grn⁻/⁻) showed more neuron loss and increased microgliosis compared with wild-type mice. The exacerbated neuron loss was due not to selective vulnerability of Grn⁻/⁻ neurons to MPTP, but rather to an increased microglial inflammatory response. Consistent with this, conditional mutants lacking PGRN in microglia exhibited MPTP-induced phenotypes similar to Grn⁻/⁻ mice. Selective depletion of PGRN from microglia in mixed cortical cultures resulted in increased death of wild-type neurons in the absence of injury. Furthermore, Grn⁻/⁻ microglia treated with LPS/IFN-γ exhibited an amplified inflammatory response, and conditioned media from these microglia promoted death of cultured neurons. Our results indicate that PGRN deficiency leads to dysregulated microglial activation and thereby contributes to increased neuron loss with injury. These findings suggest that PGRN deficiency may cause increased neuron loss in other forms of CNS injury accompanied by neuroinflammation.

  19. FOXO1 Mediates Vitamin D Deficiency-induced Insulin Resistance in Skeletal Muscle

    PubMed Central

    Chen, Songcang; Villalta, Armando; Agrawal, Devendra K.

    2015-01-01

    Prospective epidemiological studies have consistently shown a relationship between vitamin D deficiency, insulin resistance, and type 2 diabetes mellitus (DM2). This is supported by recent trials showing that vitamin D supplementation in prediabetic or insulin-resistant patients with inadequate vitamin D levels improves insulin sensitivity. However, the molecular mechanisms underlying vitamin D deficiency-induced insulin resistance and DM2 remain unknown. Skeletal muscle insulin resistance is a primary defect in the majority of patients with DM2. While sustained activation of forkhead box O1 (FOXO1) in skeletal muscle causes insulin resistance, a relationship between vitamin D deficiency and FOXO1 activation in muscle is unknown. We generated skeletal muscle-specific vitamin D receptor (VDR)-null mice and discovered that these mice developed insulin resistance and glucose intolerance accompanied by increased expression and activity of FOXO1. We also found sustained FOXO1 activation in the skeletal muscle of global VDR-null mice. Treatment of C2C12 muscle cells with 1,25-dihydroxyvitamin D (VD3) reduced FOXO1 expression, nuclear translocation, and activity. The VD3-dependent suppression of FOXO1 activation disappeared by knockdown of VDR, indicating that it is VDR-dependent. Taken together, these results suggest that FOXO1 is a critical target mediating VDR-null signaling in skeletal muscle. The novel findings provide the conceptual support that persistent FOXO1 activation may be responsible for insulin resistance and impaired glucose metabolism in vitamin D signaling-deficient mice, as well as evidence for the utility of vitamin D supplementation for intervention in DM2. PMID:26462119

  20. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.

  1. Attenuated progression of diet-induced steatohepatitis in glutathione-deficient mice.

    PubMed

    Haque, Jamil A; McMahan, Ryan S; Campbell, Jean S; Shimizu-Albergine, Masami; Wilson, Angela M; Botta, Dianne; Bammler, Theo K; Beyer, Richard P; Montine, Thomas J; Yeh, Matthew M; Kavanagh, Terrance J; Fausto, Nelson

    2010-12-01

    In nonalcoholic fatty liver disease (NAFLD), depletion of hepatic antioxidants may contribute to the progression of steatosis to nonalcoholic steatohepatitis (NASH) by increasing oxidative stress that produces lipid peroxidation, inflammation, and fibrosis. We investigated whether depletion of glutathione (GSH) increases NASH-associated hepatic pathology in mice fed a diet deficient in methionine and choline (MCD diet). Wild-type (wt) mice and genetically GSH-deficient mice lacking the modifier subunit of glutamate cysteine ligase (Gclm null mice), the rate-limiting enzyme for de novo synthesis of GSH, were fed the MCD diet, a methionine/choline-sufficient diet, or standard chow for 21 days. We assessed NASH-associated hepatic pathology, including steatosis, fibrosis, inflammation, and hepatocyte ballooning, and used the NAFLD Scoring System to evaluate the extent of changes. We measured triglyceride levels, determined the level of lipid peroxidation products, and measured by qPCR the expression of mRNAs for several proteins associated with lipid metabolism, oxidative stress, and fibrosis. MCD-fed GSH-deficient Gclm null mice were to a large extent protected from MCD diet-induced excessive fat accumulation, hepatocyte injury, inflammation, and fibrosis. Compared with wt animals, MCD-fed Gclm null mice had much lower levels of F₂-isoprostanes, lower expression of acyl-CoA oxidase, carnitine palmitoyltransferase 1a, uncoupling protein-2, stearoyl-coenzyme A desaturase-1, transforming growth factor-β, and plasminogen activator inhibitor-1 mRNAs, and higher activity of catalase, indicative of low oxidative stress, inhibition of triglyceride synthesis, and lower expression of profibrotic proteins. Global gene analysis of hepatic RNA showed that compared with wt mice, the livers of Gclm null mice have a high capacity to metabolize endogenous and exogenous compounds, have lower levels of lipogenic proteins, and increased antioxidant activity. Thus, metabolic

  2. N-Nitrosocarbaryl-induced mutagenesis in Haemophilus influenzae strains deficient in repair and recombination.

    PubMed

    Beattie, K L

    1975-02-01

    Mutagenesis was studied in repair- and recombination-deficient strains of Haemophilus influenzae after treatment with N-nitrosocarbaryl (NC). Three different strains of H. influenzae carrying mutations affecting excision-repair of UV-induced pyrimidine dimers exhibited normal repair of premutational lesions (as detected by decreased mutation yield resulting from post-treatment DNA synthesis delay) and normal nonreplicative mutation fixation. This indicated that neither of these phenomena are caused by the smae repair mechanism that removes UV-induced pyrimidine dimers from the DNA. The recombination-deficient mutant recI is apparently deficient in the replication-dependent mode of NC-induced mutation fixation. This conclusion is based on the following results: (I) NC-induced mutagenesis is lower in the recI strain than in rec+ cells. (2) Repair of premutational lesions (which depends on the existence of replication-dependent mutation fixation for its detection) was not detected in the recI strain. (3) When nonreplicative mutation fixation and final mutation frequency were measured in the same experiment, about I/4 to I/3 of the final mutation yield could be accounted for by nonreplicative mutation fixation in the rec+ strain, whereas all of the mutation could be accounted for in the recI strain by the nonreplicative mutation fixation. (4) When mutation fixation in strain dna9 recI was followed at the permissive (36 degrees) and nonpermissive (41 degrees) temperatures, it became apparent that in the recI strain replication-dependent mutation fixation occurs at early times, but these newly fixed mutations are unstable and disappear at later times, leaving only the mutations fixed by the nonreplicative process. The recI strain exhibits normal repair of NC-induced single-strand breaks or alkali-labile bonds in the DNA labeled before treatment, but is slow in joining discontinuties present in DNA synthesized after treatment. The results are consistent with the idea that

  3. Effect of insulin deficiency on the rewarding properties of methamphetamine in streptozotocin-induced diabetic rats.

    PubMed

    Bayat, Amir-Hossein; Haghparast, Abbas

    2015-01-01

    The reward is a positive behavioural response to the pleasant stimuli that can be induced by drugs, such as psychostimulants. Furthermore, diabetes mellitus is a chronic disease that many people throughout the world suffer from. Methamphetamine (METH), as a psychostimulant, engages the dopaminergic system in the reward circuitry and the synapses of dopaminergic terminals can be modified by insulin. In this study, in order to assess the effect of insulin deficiency on reward, streptozotocin (STZ)-induced diabetic animals were used as an appropriate model. One hundred and thirty-two adult male rats were divided into nine groups (three non-diabetic and six diabetic groups) to determine the most effective dose of METH (0.25, 0.5, 1 and 2mg/kg ip), and insulin replacement (10U/kg; ip) during the acquisition period in a conditioned place preference (CPP) paradigm. The diabetes model was induced by a single injection of STZ (60mg/kg; ip). The conditioning score was considered to be the difference in time spent in drug- and saline-paired compartments. The results demonstrated that the most effective doses of METH were 1 and 2mg/kg in non-diabetic animals. Although the place preference was not shown in non-diabetic animals at the dose of 0.5mg/kg, this dose significantly induced place preference to METH in STZ-diabetic rats. Additionally, insulin replacement could reverse the METH-induced CPP in diabetic animals. Our findings suggest that the positive effect of insulin deficiency on METH rewarding properties is dependent on insulin level in part, and the replacement of the insulin in diabetic rats as a treatment can improve the rewarding properties of METH.

  4. ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12) Interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) Linking Iron Deficiency and Oxidative Stress Responses.

    PubMed

    Le, Cham Thi Tuyet; Brumbarova, Tzvetina; Ivanov, Rumen; Stoof, Claudia; Weber, Eva; Mohrbacher, Julia; Fink-Straube, Claudia; Bauer, Petra

    2016-01-01

    Plants grown under iron (Fe)-deficient conditions induce a set of genes that enhance the efficiency of Fe uptake by the roots. In Arabidopsis (Arabidopsis thaliana), the central regulator of this response is the basic helix-loop-helix transcription factor FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT). FIT activity is regulated by protein-protein interactions, which also serve to integrate external signals that stimulate and possibly inhibit Fe uptake. In the search of signaling components regulating FIT function, we identified ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12), an abiotic stress-induced transcription factor. ZAT12 interacted with FIT, dependent on the presence of the ethylene-responsive element-binding factor-associated amphiphilic repression motif. ZAT12 protein was found expressed in the root early differentiation zone, where its abundance was modulated in a root layer-specific manner. In the absence of ZAT12, FIT expression was upregulated, suggesting a negative effect of ZAT12 on Fe uptake. Consistently, zat12 loss-of-function mutants had higher Fe content than the wild type at sufficient Fe. We found that under Fe deficiency, hydrogen peroxide (H2O2) levels were enhanced in a FIT-dependent manner. FIT protein, in turn, was stabilized by H2O2 but only in the presence of ZAT12, showing that H2O2 serves as a signal for Fe deficiency responses. We propose that oxidative stress-induced ZAT12 functions as a negative regulator of Fe acquisition. A model where H2O2 mediates the negative regulation of plant responses to prolonged stress might be applicable to a variety of stress conditions. PMID:26556796

  5. ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12) Interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) Linking Iron Deficiency and Oxidative Stress Responses.

    PubMed

    Le, Cham Thi Tuyet; Brumbarova, Tzvetina; Ivanov, Rumen; Stoof, Claudia; Weber, Eva; Mohrbacher, Julia; Fink-Straube, Claudia; Bauer, Petra

    2016-01-01

    Plants grown under iron (Fe)-deficient conditions induce a set of genes that enhance the efficiency of Fe uptake by the roots. In Arabidopsis (Arabidopsis thaliana), the central regulator of this response is the basic helix-loop-helix transcription factor FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT). FIT activity is regulated by protein-protein interactions, which also serve to integrate external signals that stimulate and possibly inhibit Fe uptake. In the search of signaling components regulating FIT function, we identified ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12), an abiotic stress-induced transcription factor. ZAT12 interacted with FIT, dependent on the presence of the ethylene-responsive element-binding factor-associated amphiphilic repression motif. ZAT12 protein was found expressed in the root early differentiation zone, where its abundance was modulated in a root layer-specific manner. In the absence of ZAT12, FIT expression was upregulated, suggesting a negative effect of ZAT12 on Fe uptake. Consistently, zat12 loss-of-function mutants had higher Fe content than the wild type at sufficient Fe. We found that under Fe deficiency, hydrogen peroxide (H2O2) levels were enhanced in a FIT-dependent manner. FIT protein, in turn, was stabilized by H2O2 but only in the presence of ZAT12, showing that H2O2 serves as a signal for Fe deficiency responses. We propose that oxidative stress-induced ZAT12 functions as a negative regulator of Fe acquisition. A model where H2O2 mediates the negative regulation of plant responses to prolonged stress might be applicable to a variety of stress conditions.

  6. Salt intake and iodine status of women in Samoa.

    PubMed

    Land, Mary-Anne; Webster, Jacqui L; Ma, Gary; Li, Mu; Su'a, Sarah Asi Faletoese; Ieremia, Merina; Viali, Satu; Faeamani, Gavin; Bell, A Colin; Quested, Christine; Neal, Bruce C; Eastman, Creswell J

    2016-01-01

    The objective of this study was to determine iodine nutrition status and whether iodine status differs across salt intake levels among a sample of women aged 18-45 years living in Samoa. A cross-sectional survey was completed and 24-hr urine samples were collected and assessed for iodine (n=152) and salt excretion (n=119). The median urinary iodine concentration (UIC) among the women was 88 μg/L (Interquartile range (IQR)=54-121 μg/L). 62% of the women had a UIC <100 μg/L. The crude estimated mean 24-hr urinary salt excretion was 6.6 (standard deviation 3.2) g/day. More than two-thirds (66%) of the women exceeded the World Health Organization recommended maximum level of 5 g/day. No association was found between median UIC and salt excretion (81 μg/L iodine where urinary salt excretion >=5 g/day versus 76 μg/L where urinary salt excretion <5 g/day; p=0.4). Iodine nutrition appears to be insufficient in this population and may be indicative of iodine deficiency disorders in Samoan women. A collaborative approach in monitoring iodine status and salt intake will strengthen both programs and greatly inform the level of iodine fortification required to ensure optimal iodine intake as population salt reduction programs take effect. PMID:26965773

  7. Salt intake and iodine status of women in Samoa.

    PubMed

    Land, Mary-Anne; Webster, Jacqui L; Ma, Gary; Li, Mu; Su'a, Sarah Asi Faletoese; Ieremia, Merina; Viali, Satu; Faeamani, Gavin; Bell, A Colin; Quested, Christine; Neal, Bruce C; Eastman, Creswell J

    2016-01-01

    The objective of this study was to determine iodine nutrition status and whether iodine status differs across salt intake levels among a sample of women aged 18-45 years living in Samoa. A cross-sectional survey was completed and 24-hr urine samples were collected and assessed for iodine (n=152) and salt excretion (n=119). The median urinary iodine concentration (UIC) among the women was 88 μg/L (Interquartile range (IQR)=54-121 μg/L). 62% of the women had a UIC <100 μg/L. The crude estimated mean 24-hr urinary salt excretion was 6.6 (standard deviation 3.2) g/day. More than two-thirds (66%) of the women exceeded the World Health Organization recommended maximum level of 5 g/day. No association was found between median UIC and salt excretion (81 μg/L iodine where urinary salt excretion >=5 g/day versus 76 μg/L where urinary salt excretion <5 g/day; p=0.4). Iodine nutrition appears to be insufficient in this population and may be indicative of iodine deficiency disorders in Samoan women. A collaborative approach in monitoring iodine status and salt intake will strengthen both programs and greatly inform the level of iodine fortification required to ensure optimal iodine intake as population salt reduction programs take effect.

  8. Paradoxical resistance to diet-induced obesity in UCP1-deficient mice

    PubMed Central

    Liu, Xiaotuan; Rossmeisl, Martin; McClaine, Jennifer; Kozak, Leslie P.

    2003-01-01

    The availability of mice lacking the mitochondrial uncoupling protein UCP1, has provided an opportunity to analyze the relationship between the capacity for energy expenditure and the development of obesity in response to a high-fat, high-sucrose diet. Congenic UCP1-deficient mice on a C57BL/6J genetic background show a temperature-dependent resistance to diet-induced obesity when compared with wild-type mice. This resistance, which occurs at 20°C, is quickly reversed when the ambient temperature is increased to 27°C. At 20°C, total oxygen consumption and physical activity of mutant and wild-type mice are indistinguishable; however, body temperature is higher in UCP1-deficient mice by 0.1–0.3°C, and respiratory quotient is slightly reduced. A reduced respiratory quotient, together with elevated β-hydroxybutyrate and reduced plasma fatty acid levels, suggests that the mutants oxidize a greater proportion of fat than wild-type mice, and that this possibly accounts for the resistance to diet-induced obesity. Although shivering is one alternative mechanism of thermogenesis that is probably used in UCP1-deficient mice, whether there are others remains to be determined. Nevertheless, our study underscores the paradox that elimination of the major thermogenic mechanism in the animal reduces rather than increases metabolic efficiency. We propose that in the absence of nonshivering thermogenesis, alternative, calorically more costly pathways of metabolism must be used to maintain body temperature. PMID:12569166

  9. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial.

    PubMed

    Basaria, Shehzad; Travison, Thomas G; Alford, Daniel; Knapp, Philip E; Teeter, Kjersten; Cahalan, Christine; Eder, Richard; Lakshman, Kishore; Bachman, Eric; Mensing, George; Martel, Marc O; Le, Dillon; Stroh, Helene; Bhasin, Shalender; Wasan, Ajay D; Edwards, Robert R

    2015-02-01

    Symptomatic androgen deficiency is common in patients taking opioid analgesics, as these drugs potently suppress the hypothalamic-pituitary-gonadal axis. However, the efficacy of testosterone replacement in this setting remains unclear. The objective of this trial was to evaluate the efficacy of testosterone replacement on pain perception and other androgen-dependent outcomes in men with opioid-induced androgen deficiency. We conducted a randomized, double-blind, parallel placebo-controlled trial at an outpatient academic research center. Participants were men aged 18 to 64 years on opioid analgesics for chronic noncancer pain, and total testosterone levels were <350 ng/dL. Participants were randomly assigned to 14 weeks of daily transdermal gel that contained 5 g of testosterone or placebo. Primary outcomes were changes in self-reported clinical pain and objectively assessed pain sensitivity. Sexual function, quality of life, and body composition were also assessed. The mean age was 49 years. The median total and free testosterone levels at baseline were 243 ng/dL and 47 pg/mL and 251 ng/dL and 43 pg/mL in the testosterone and placebo arm, respectively. Of the 84 randomized participants, 65 had follow-up data on efficacy outcomes. Compared with men assigned to the placebo arm, those assigned to testosterone replacement experienced greater improvements in pressure and mechanical hyperalgesia, sexual desire, and role limitation due to emotional problems. Testosterone administration was also associated with an improvement in body composition. There were no between-group differences in changes in self-reported pain. In conclusion, in men with opioid-induced androgen deficiency, testosterone administration improved pain sensitivity, sexual desire, body composition, and aspects of quality of life.

  10. Vitamin A Deficiency Promotes Inflammation by Induction of Type 2 Cytokines in Experimental Ovalbumin-Induced Asthma Murine Model.

    PubMed

    Cui, Weiwei; Zhang, Peng; Gu, Jingmin; Tian, Yuan; Gao, Xiuzhu; Liu, Yaqing; Jin, Zheng; Yan, Dongmei; Zhu, Xun; Li, Dong

    2016-10-01

    Vitamin A (VA) deficiency is one of the most common malnutrition conditions. Recent reports showed that VA plays an important role in the immune balance; lack of VA could result in enhanced type 2 immune response characterized by increased type 2 cytokine production and type 2 innate lymphoid cell infiltration and activation. Type 2 immune response plays protective role in anti-infection but plays pathological role in asthmatic disease. In order to investigate the role of VA in the asthmatic disease, we used ovalbumin-induced asthma murine model and observed the pathological changes between mouse-received VA-deficient and VA-sufficient diets. We also measured the type 2 cytokine expressions to reveal the potential mechanism. Our results showed that VA deficiency exacerbates ovalbumin-induced lung inflammation and type 2 cytokine productions. Thus, VA deficiency, or malnutrition in further extent, may contribute to the increasing prevalence of asthma. PMID:27525423

  11. Inhomogeneous width of oxygen-deficient centers induced by electron irradiation of silica

    SciTech Connect

    D'Amico, Michele; Leone, Maurizio; Messina, Fabrizio; Cannas, Marco; Boscaino, Roberto

    2009-02-01

    We report a study of the luminescence activity of oxygen-deficient centers stabilized in as-grown synthetic silica, as compared with the same defects induced by {beta} irradiation at increasing doses, ranging from 1.2x10{sup 3} to 5x10{sup 6} kGy. We experimentally observe a progressive broadening of the luminescence band with increasing total electron dose released on samples. By analyzing our data within a theoretical model capable of separating homogeneous and inhomogeneous contribution to the total luminescence linewidth, we observe that the increasing of the width is entirely ascribable to the inhomogeneous component which increases, in the most irradiated sample, of 60% with respect to the value in the as-grown sample. This effect can be due either to the progressive creation of new defects statistically exploring different sites of the matrix, or to a progressive structural transformation of silica host which affects the optical properties of induced point defects.

  12. Diet-Induced Obesity and Reduced Skin Cancer Susceptibility in Matrix Metalloproteinase 19-Deficient Mice

    PubMed Central

    Pendás, Alberto M.; Folgueras, Alicia R.; Llano, Elena; Caterina, John; Frerard, Françoise; Rodríguez, Francisco; Astudillo, Aurora; Noël, Agnès; Birkedal-Hansen, Henning; López-Otín, Carlos

    2004-01-01

    Matrix metalloproteinase 19 (MMP-19) is a member of the MMP family of endopeptidases that, in contrast to most MMPs, is widely expressed in human tissues under normal quiescent conditions. MMP-19 has been found to be associated with ovulation and angiogenic processes and is deregulated in diverse pathological conditions such as rheumatoid arthritis and cancer. To gain further insights into the in vivo functions of this protease, we have generated mutant mice deficient in Mmp19. These mice are viable and fertile and do not display any obvious abnormalities. However, Mmp19-null mice develop a diet-induced obesity due to adipocyte hypertrophy and exhibit decreased susceptibility to skin tumors induced by chemical carcinogens. Based on these results, we suggest that this enzyme plays an in vivo role in some of the tissue remodeling events associated with adipogenesis, as well as in pathological processes such as tumor progression. PMID:15169894

  13. Mice heterozygous for cathepsin D deficiency exhibit mania-related behavior and stress-induced depression.

    PubMed

    Zhou, Rui; Lu, Yi; Han, Yong; Li, Xia; Lou, Huifang; Zhu, Liya; Zhen, Xuechu; Duan, Shumin

    2015-12-01

    Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live into adulthood psychopathological symptoms have not been reported. Extensive neuropathology and altered neurotransmission have been reported in CTSD-deficient mice; however signs of neuropsychiatric behavior in these mice are not well characterized due to the severe movement disorder and premature death of the animal. In the present study, we show that heterozygous CTSD-deficient (CTSD HET) mice display an overall behavioral profile that is similar to human mania, including hyperlocomotion, d-amphetamine-induced hyperactivity, sleep-disturbance, and reduced anxiety-like behavior. However, under stressful conditions CTSD HET mice manifest depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities. In addition, CTSD HET mice display stress-induced hypersecretion of corticosterone. These findings suggest an important role for CTSD in the regulation of mood stabilization.

  14. Gibberellin deficiency pleiotropically induces culm bending in sorghum: an insight into sorghum semi-dwarf breeding

    PubMed Central

    Ordonio, Reynante L.; Ito, Yusuke; Hatakeyama, Asako; Ohmae-Shinohara, Kozue; Kasuga, Shigemitsu; Tokunaga, Tsuyoshi; Mizuno, Hiroshi; Kitano, Hidemi; Matsuoka, Makoto; Sazuka, Takashi

    2014-01-01

    Regulation of symmetrical cell growth in the culm is important for proper culm development. So far, the involvement of gibberellin (GA) in this process has not yet been demonstrated in sorghum. Here, we show that GA deficiency resulting from any loss-of-function mutation in four genes (SbCPS1, SbKS1, SbKO1, SbKAO1) involved in the early steps of GA biosynthesis, not only results in severe dwarfism but also in abnormal culm bending. Histological analysis of the bent culm revealed that the intrinsic bending was due to an uneven cell proliferation between the lower and upper sides of culm internodes. GA treatment alleviated the bending and dwarfism in mutants, whereas the GA biosynthesis inhibitor, uniconazole, induced such phenotypes in wild-type plants— both in a concentration-dependent manner, indicating an important role of GA in controlling erectness of the sorghum culm. Finally, we propose that because of the tight relationship between GA deficiency-induced dwarfism and culm bending in sorghum, GA-related mutations have unlikely been selected in the history of sorghum breeding, as could be inferred from previous QTL and association studies on sorghum plant height that did not pinpoint GA-related genes. PMID:24924234

  15. Gibberellin deficiency pleiotropically induces culm bending in sorghum: an insight into sorghum semi-dwarf breeding.

    PubMed

    Ordonio, Reynante L; Ito, Yusuke; Hatakeyama, Asako; Ohmae-Shinohara, Kozue; Kasuga, Shigemitsu; Tokunaga, Tsuyoshi; Mizuno, Hiroshi; Kitano, Hidemi; Matsuoka, Makoto; Sazuka, Takashi

    2014-06-13

    Regulation of symmetrical cell growth in the culm is important for proper culm development. So far, the involvement of gibberellin (GA) in this process has not yet been demonstrated in sorghum. Here, we show that GA deficiency resulting from any loss-of-function mutation in four genes (SbCPS1, SbKS1, SbKO1, SbKAO1) involved in the early steps of GA biosynthesis, not only results in severe dwarfism but also in abnormal culm bending. Histological analysis of the bent culm revealed that the intrinsic bending was due to an uneven cell proliferation between the lower and upper sides of culm internodes. GA treatment alleviated the bending and dwarfism in mutants, whereas the GA biosynthesis inhibitor, uniconazole, induced such phenotypes in wild-type plants--both in a concentration-dependent manner, indicating an important role of GA in controlling erectness of the sorghum culm. Finally, we propose that because of the tight relationship between GA deficiency-induced dwarfism and culm bending in sorghum, GA-related mutations have unlikely been selected in the history of sorghum breeding, as could be inferred from previous QTL and association studies on sorghum plant height that did not pinpoint GA-related genes.

  16. Deficiency in Apoptosis-Inducing Factor Recapitulates Chronic Kidney Disease via Aberrant Mitochondrial Homeostasis.

    PubMed

    Coughlan, Melinda T; Higgins, Gavin C; Nguyen, Tuong-Vi; Penfold, Sally A; Thallas-Bonke, Vicki; Tan, Sih Min; Ramm, Georg; Van Bergen, Nicole J; Henstridge, Darren C; Sourris, Karly C; Harcourt, Brooke E; Trounce, Ian A; Robb, Portia M; Laskowski, Adrienne; McGee, Sean L; Genders, Amanda J; Walder, Ken; Drew, Brian G; Gregorevic, Paul; Qian, Hongwei; Thomas, Merlin C; Jerums, George; Macisaac, Richard J; Skene, Alison; Power, David A; Ekinci, Elif I; Wijeyeratne, Xiaonan W; Gallo, Linda A; Herman-Edelstein, Michal; Ryan, Michael T; Cooper, Mark E; Thorburn, David R; Forbes, Josephine M

    2016-04-01

    Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency in AIF is known to result in defective oxidative phosphorylation (OXPHOS), via loss of complex I activity and assembly in other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that a decrease in AIF would result in chronic kidney disease (CKD). Here, we report that partial knockdown of Aif in mice recapitulates many features of CKD, in association with a compensatory increase in the mitochondrial ATP pool via a shift toward mitochondrial fusion, excess mitochondrial reactive oxygen species production, and Nox4 upregulation. However, despite a 50% lower AIF protein content in the kidney cortex, there was no loss of complex I activity or assembly. When diabetes was superimposed onto Aif knockdown, there were extensive changes in mitochondrial function and networking, which augmented the renal lesion. Studies in patients with diabetic nephropathy showed a decrease in AIF within the renal tubular compartment and lower AIFM1 renal cortical gene expression, which correlated with declining glomerular filtration rate. Lentiviral overexpression of Aif1m rescued glucose-induced disruption of mitochondrial respiration in human primary proximal tubule cells. These studies demonstrate that AIF deficiency is a risk factor for the development of diabetic kidney disease. PMID:26822084

  17. RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice.

    PubMed

    Delbridge, Alex R D; Pang, Swee Heng Milon; Vandenberg, Cassandra J; Grabow, Stephanie; Aubrey, Brandon J; Tai, Lin; Herold, Marco J; Strasser, Andreas

    2016-09-19

    Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53(-/-) mice. Thus, potentially oncogenic DNA lesions are likely to also trigger apoptosis through additional, p53-independent processes. We found that loss of the BH3-only protein BIM accelerated lymphoma development in p53-deficient mice. This process was negated by concomitant loss of RAG1/2-mediated antigen receptor gene rearrangement. This demonstrates that BIM is critical for the induction of apoptosis caused by potentially oncogenic DNA lesions elicited by RAG1/2-induced gene rearrangement. Furthermore, this highlights the role of a BIM-mediated tumor suppressor pathway that acts in parallel to the p53 pathway and remains active even in the absence of wild-type p53 function, suggesting this may be exploited in the treatment of p53-deficient cancers. PMID:27621418

  18. Role of iodine, selenium and other micronutrients in thyroid function and disorders.

    PubMed

    Triggiani, Vincenzo; Tafaro, Emilio; Giagulli, Vito Angelo; Sabbà, Carlo; Resta, Francesco; Licchelli, Brunella; Guastamacchia, Edoardo

    2009-09-01

    Micronutrients, mostly iodine and selenium, are required for thyroid hormone synthesis and function. Iodine is an essential component of thyroid hormones and its deficiency is considered as the most common cause of preventable brain damage in the world. Nowadays about 800 million people are affected by iodine deficiency disorders that include goiter, hypothyroidism, mental retardation, and a wide spectrum of other growth and developmental abnormalities. Iodine supplementation, under form of iodized salt and iodized vegetable oil, produced dramatic improvements in many areas, even though iodine deficiency is still a problem not only for developing countries. In fact, certain subpopulations like vegetarians may not reach an adequate iodine intake even in countries considered iodine-sufficient. A reduction in dietary iodine content could also be related to increased adherence to dietary recommendations to reduce salt intake for preventing hypertension. Furthermore, iodine intakes are declining in many countries where, after endemic goiter eradication, the lack of monitoring of iodine nutrition can lead to a reappearance of goiter and other iodine deficiency disorders. Three different selenium-dependent iodothyronine deiodinases (types I, II, and III) can both activate and inactivate thyroid hormones, making selenium an essential micronutrient for normal development, growth, and metabolism. Furthermore, selenium is found as selenocysteine in the catalytic center of enzymes protecting the thyroid from free radicals damage. In this way, selenium deficiency can exacerbate the effects of iodine deficiency and the same is true for vitamin A or iron deficiency. Substances introduced with food, such as thiocyanate and isoflavones or certain herbal preparations, can interfere with micronutrients and influence thyroid function. Aim of this paper is to review the role of micronutrients in thyroid function and diseases. PMID:19594417

  19. TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis

    PubMed Central

    Beyer, Katharina; Stollhof, Laura; Poetschke, Christian; von Bernstorff, Wolfram; Partecke, Lars Ivo; Diedrich, Stephan; Maier, Stefan; Bröker, Barbara M; Heidecke, Claus-Dieter

    2016-01-01

    Background Apart from inducing apoptosis in tumor cells, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) influences inflammatory reactions. Murine colon ascendens stent peritonitis (CASP) represents a model of diffuse peritonitis. Recently, it has been demonstrated that administration of exogenous TRAIL not only induces apoptosis in neutrophils but also enhances survival in this model. The aim of this study was to examine the impact of genetic TRAIL deficiency on the course of CASP. Methods Peritonitis was induced in 6- to 8-week-old female TRAIL−/− mice as well as in wild-type mice. The sepsis severity score and survival of mice were monitored. Bacterial loads in blood as well as in the lymphoid organs were examined. Additionally, the number of apoptotic cells within the lymphoid organs was determined. Results As early as 8 hours postinduction of CASP, TRAIL−/− mice were significantly more affected by sepsis than wild-type mice, as measured by the sepsis severity score. However, during the further course of sepsis, TRAIL deficiency led to significantly decreased sepsis severity scores, resulting in an enhanced overall survival in TRAIL−/− mice. The better survival of TRAIL−/− mice was accompanied by a decreased bacterial load within the blood. In marked contrast, the number of apoptotic cells within the lymphoid organs was highly increased in TRAIL−/− mice 20 hours after induction of CASP. Conclusion Hence, exogenous and endogenous TRAIL is protective during the early phase of sepsis, while endogenous TRAIL appears to be detrimental in the later course of this disease. PMID:27366100

  20. Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

    PubMed

    Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

    2016-03-01

    Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner.

  1. Low molybdenum state induced by tungsten as a model of molybdenum deficiency in rats.

    PubMed

    Yoshida, Munehiro; Nakagawa, Mikihito; Hosomi, Ryota; Nishiyama, Toshimasa; Fukunaga, Kenji

    2015-05-01

    Organ molybdenum (Mo) concentration and the activity of hepatic sulfite oxidase and xanthine oxidase were compared in tungsten-administered rats as well as rats fed with a low Mo diet to evaluate the use of tungsten-administered rats as a model of Mo deficiency. Twenty-four male 6-week-old Wistar rats were divided into four groups according to diet (AIN93G diet (control diet) or the control diet minus ammonium molybdate (low Mo diet)) and drinking water (deionized water or deionized water containing 200 μg/mL tungsten in the form of sodium tungstate). Mo content in the control and low Mo diets were 196 and 42 ng/g, respectively. Intake of the low Mo diet significantly reduced the Mo content of several organs and serum. Decrease in hepatic sulfite oxidase activity was also induced by the low Mo diet. The administration of tungsten induced marked decreases in organ Mo content and the activity of hepatic sulfite oxidase and xanthine oxidase. These decreases induced by tungsten administration were more pronounced than those induced by just a low Mo diet. Serum uric acid was also reduced by tungsten administration irrespective of Mo intake. Although a comparatively high accumulation of tungsten (3 to 9 μg/g) was observed in the kidneys and liver, adverse effects of tungsten accumulation on liver and kidney function were not observed in serum biochemical tests. These results indicate that tungsten-administered animals may be used as a model of Mo deficiency. PMID:25627419

  2. FAD-induced in vitro activation of glutathione reductase in the lens of B2 deficient rats.

    PubMed

    Ono, S; Hirano, H

    1984-04-01

    We studied the FAD-induced in vitro stimulation of lenticular glutathione reductase in riboflavin-deficient rats. The stimulatory effect of FAD on lenticular glutathione reductase in rats fed a B2-deficient diet for 4 weeks was remarkably higher than in paired control rats fed a B2-supplemented basal diet and control rats had ad libitum access to a B2-supplemented basal diet. The in vitro FAD stimulation effect on rat lenticular glutathione reductase represents a sensitive indicator of the B2 deficient status.

  3. Assessing iodine intake, iodine status, and the effects of maternal iodine supplementation: introduction to articles arising from 3 workshops held by the NIH Office of Dietary Supplements.

    PubMed

    Ershow, Abby G; Goodman, Gay; Coates, Paul M; Swanson, Christine A

    2016-09-01

    The NIH Office of Dietary Supplements (ODS) convened 3 workshops on iodine nutrition in 2014, each held in Rockville, Maryland. These workshops were part of the ongoing ODS Iodine Initiative, begun in 2011 in response to concerns that US pregnant women may be at risk of iodine deficiency and that a high fraction of prenatal dietary supplements do not contain the recommended amounts of iodine. The primary purpose of the workshops was to consider the data and resources necessary to evaluate the clinical and public health benefits and risks of maternal iodine supplementation in the United States. The first workshop focused on the assessment of iodine intake, the second focused on the assessment of iodine status, and the third focused on the design and interpretation of clinical trials of maternal iodine supplementation. Here we provide the background of the ODS Iodine Initiative, summarize the 3 workshops held in 2014, and introduce the articles that arose from the workshops and are published in this supplement issue. PMID:27534646

  4. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation.

    PubMed

    Bluett, R J; Gamble-George, J C; Hermanson, D J; Hartley, N D; Marnett, L J; Patel, S

    2014-07-08

    Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using the light-dark box assay and novelty-induced hypophagia test. Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. FAAH inhibition does not significantly affect anxiety-like behaviors in non-stressed mice. Moreover, whole brain anandamide levels are reduced 24 h after acute foot-shock stress and are negatively correlated with anxiety-like behavioral measures in the light-dark box test. These data indicate that central anandamide levels predict acute stress-induced anxiety, and that reversal of stress-induced anandamide deficiency is a key mechanism subserving the therapeutic effects of FAAH inhibition. These studies provide further support that eCB-augmentation is a viable pharmacological strategy for the treatment of stress-related neuropsychiatric disorders.

  5. Iodine insufficiency: a global health problem?

    PubMed

    Swanson, Christine A; Pearce, Elizabeth N

    2013-09-01

    As a result of collaborative efforts with international organizations and the salt industry, many developing and developed countries practice universal salt iodization (USI) or have mandatory salt fortification programs. As a consequence, the prevalence of iodine deficiency decreased dramatically. The United States and Canada are among the few developed countries that do not practice USI. Such an undertaking would require evidence of deficiency among vulnerable population groups, including pregnant women, newborns, and developing infants. Government agencies in the United States rely heavily on data from NHANES to assess the iodine status of the general population and pregnant women in particular. NHANES data suggest that pregnant women in the United States remain mildly deficient. This is important, because the developing fetus is dependent on maternal iodine intake for normal brain development throughout pregnancy. Professional societies have recommended that pregnant and lactating women, or those considering pregnancy, consume a supplement providing 150 μg iodine daily. The United States and Canada collaborate on the daily recommended intake and are also confronted with the challenge of identifying the studies needed to determine if USI is likely to be beneficial to vulnerable population groups without exposing them to harm.

  6. Iodine insufficiency: a global health problem?

    PubMed

    Swanson, Christine A; Pearce, Elizabeth N

    2013-01-01

    As a result of collaborative efforts with international organizations and the salt industry, many developing and developed countries practice universal salt iodization (USI) or have mandatory salt fortification programs. As a consequence, the prevalence of iodine deficiency decreased dramatically. The United States and Canada are among the few developed countries that do not practice USI. Such an undertaking would require evidence of deficiency among vulnerable population groups, including pregnant women, newborns, and developing infants. Government agencies in the United States rely heavily on data from NHANES to assess the iodine status of the general population and pregnant women in particular. NHANES data suggest that pregnant women in the United States remain mildly deficient. This is important, because the developing fetus is dependent on maternal iodine intake for normal brain development throughout pregnancy. Professional societies have recommended that pregnant and lactating women, or those considering pregnancy, consume a supplement providing 150 μg iodine daily. The United States and Canada collaborate on the daily recommended intake and are also confronted with the challenge of identifying the studies needed to determine if USI is likely to be beneficial to vulnerable population groups without exposing them to harm. PMID:24038248

  7. Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity.

    PubMed

    Bauer, Alison K; Faiola, Brenda; Abernethy, Diane J; Marchan, Rosemarie; Pluta, Linda J; Wong, Victoria A; Gonzalez, Frank J; Butterworth, Byron E; Borghoff, Susan J; Everitt, Jeffrey I; Recio, Leslie

    2003-04-01

    Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene-induced toxicity. Male and female mEH-deficient (mEH-/-) mice and background mice (129/Sv) were exposed to inhaled benzene (0, 10, 50, or 100 ppm) 5 days/week, 6 h/day, for a two-week duration. Total white blood cell counts and bone marrow cell counts were used to assess hematotoxicity and myelotoxicity. Micronucleated peripheral blood cells were counted to assess genotoxicity, and the p21 mRNA level in bone marrow cells was used as a determinant of the p53-regulated DNA damage response. Male mEH-/- mice did not have any significant hematotoxicity or myelotoxicity at the highest benzene exposure compared to the male 129/Sv mice. Significant hematotoxicity or myelotoxicity did not occur in the female mEH-/- or 129/Sv mice. Male mEH-/- mice were also unresponsive to benzene-induced genotoxicity compared to a significant induction in the male 129/Sv mice. The female mEH-/- and 129/Sv mice were virtually unresponsive to benzene-induced genotoxicity. While p21 mRNA expression was highly induced in male 129/Sv mice after exposure to 100-ppm benzene, no significant alteration was observed in male mEH-/- mice. Likewise, p21 mRNA expression in female mEH-/- mice was not significantly induced upon benzene exposure whereas a significant induction was observed in female 129/Sv mice. Thus mEH appears to be critical in benzene-induced toxicity in male, but not female, mice.

  8. Iodine nutrition among indigenous Tarahumara schoolchildren in Mexico.

    PubMed

    Monárrez-Espino, J; Greiner, T

    2005-10-01

    This paper adds iodine data to the nutritional survey recently published in the Eur J Clin Nutr (2004;58:532-540) to identify growth retardation and micronutrient deficiencies among Tarahumara children from five selected indigenous boarding schools in Mexico. Total goiter rate (TGR) (n=384), urinary iodine concentrations (UI) (n = 100), and iodine content of salt were measured. Overall, TGR was 7.0% (grade 1 = 6.8%, grade 2 = 0.2%). The median UI of the group was 125 microg/l, while the median UI across the schools ranged from 92.0-156.5 microg/l, with 32 and 6% of the children having UI between 50-99 microg/l and 20-49 microg/l, respectively. The iodine content in all the salt packages checked at the schools was above 25 parts per million. Based on TGR and UI, there is a marginal iodine deficiency in this sample of children, probably due to an insufficient iodine intake. These results add to existing evidence that iodine deficiency still constitutes a public health problem in certain populations living in the mountainous regions in Mexico.

  9. Myeloperoxidase deficiency induces MIP-2 production via ERK activation in zymosan-stimulated mouse neutrophils.

    PubMed

    Tateno, N; Matsumoto, N; Motowaki, T; Suzuki, K; Aratani, Y

    2013-05-01

    Myeloperoxidase (MPO), a major constituent of neutrophils, catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion. We have previously reported that MPO-deficient (MPO(-/-)) neutrophils produce greater amount of macrophage inflammatory protein-2 (MIP-2) in vitro than do wild type when stimulated with zymosan. In this study, we investigated the molecular mechanisms governing the up-regulation of MIP-2 production in the mutant neutrophils. Interestingly, we found that zymosan-induced production of MIP-2 was blocked by pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK), and with BAY11-7082, an inhibitor of nuclear factor (NF)-κB. Western blot analysis indicated that U0126 also inhibited the phosphorylation of p65 subunit of NF-κB (p65), indicating that MIP-2 was produced via the ERK/NF-κB pathway. Intriguingly, we found that ERK1/2, p65, and alpha subunit of inhibitor of κB (IκBα) in the MPO(-/-) neutrophils were phosphorylated more strongly than in the wild type when stimulated with zymosan. Exogenous H2O2 treatment in addition to zymosan stimulation enhanced the phosphorylation of ERK1/2 without affecting the zymosan-induced MIP-2 production. In contrast, exogenous HOCl inhibited the production of MIP-2 as well as IκBα phosphorylation without affecting ERK activity. The zymosan-induced production of MIP-2 in the wild-type neutrophils was enhanced by pre-treatment of the MPO inhibitor 4-aminobenzoic acid hydrazide. Collectively, these results strongly suggest that both lack of HOCl and accumulation of H2O2 due to MPO deficiency contribute to the up-regulation of MIP-2 production in mouse neutrophils stimulated with zymosan.

  10. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    SciTech Connect

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei

    2015-03-06

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

  11. Myeloperoxidase deficiency induces MIP-2 production via ERK activation in zymosan-stimulated mouse neutrophils.

    PubMed

    Tateno, N; Matsumoto, N; Motowaki, T; Suzuki, K; Aratani, Y

    2013-05-01

    Myeloperoxidase (MPO), a major constituent of neutrophils, catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion. We have previously reported that MPO-deficient (MPO(-/-)) neutrophils produce greater amount of macrophage inflammatory protein-2 (MIP-2) in vitro than do wild type when stimulated with zymosan. In this study, we investigated the molecular mechanisms governing the up-regulation of MIP-2 production in the mutant neutrophils. Interestingly, we found that zymosan-induced production of MIP-2 was blocked by pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK), and with BAY11-7082, an inhibitor of nuclear factor (NF)-κB. Western blot analysis indicated that U0126 also inhibited the phosphorylation of p65 subunit of NF-κB (p65), indicating that MIP-2 was produced via the ERK/NF-κB pathway. Intriguingly, we found that ERK1/2, p65, and alpha subunit of inhibitor of κB (IκBα) in the MPO(-/-) neutrophils were phosphorylated more strongly than in the wild type when stimulated with zymosan. Exogenous H2O2 treatment in addition to zymosan stimulation enhanced the phosphorylation of ERK1/2 without affecting the zymosan-induced MIP-2 production. In contrast, exogenous HOCl inhibited the production of MIP-2 as well as IκBα phosphorylation without affecting ERK activity. The zymosan-induced production of MIP-2 in the wild-type neutrophils was enhanced by pre-treatment of the MPO inhibitor 4-aminobenzoic acid hydrazide. Collectively, these results strongly suggest that both lack of HOCl and accumulation of H2O2 due to MPO deficiency contribute to the up-regulation of MIP-2 production in mouse neutrophils stimulated with zymosan. PMID:23438680

  12. Assessing infant cognitive development after prenatal iodine supplementation.

    PubMed

    Bell, Martha Ann; Ross, Alleyne P; Goodman, Gay

    2016-09-01

    Little information is available on infant behavioral development outcomes of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Studies performed to date, all of which relied on global developmental assessments, have yielded inconsistent findings with regard to psychomotor development, negative findings with regard to mental development, and no information as to the development of specific cognitive functions. Our review of these studies leads us to suspect that the use of global developmental assessments might partially explain the negative and inconsistent findings. To identify cognitive processes that might be sensitive to prenatal iodine supplementation, we examined the timing of thyroid hormone action on specific brain systems. The development of infant visual attention is sensitive to thyroid hormone during the early prenatal period, when the fetus is entirely dependent on maternal thyroid hormone. For this reason, infant visual attention has the potential to be a sensitive measure of infant outcomes in prenatal iodine supplementation studies. We suggest the assessment of infant visual attention, with follow-up examination of childhood executive functions, as a means of capturing the effects of maternal iodine deficiency and prenatal iodine supplementation on specific cognitive processes. In particular, we propose comparison of infant performance on global developmental tests and specialized tests of visual attention in pilot trials of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Only by comparing the 2 types of tests side by side will it be possible to establish whether the use of a sensitive measure of infant visual attention will increase the reliability of such supplementation studies. Recognizing that exposure misclassification may also provide a partial explanation for the inconsistent neurodevelopmental outcomes in previous studies, we suggest that urinary iodine concentration or

  13. Assessing infant cognitive development after prenatal iodine supplementation.

    PubMed

    Bell, Martha Ann; Ross, Alleyne P; Goodman, Gay

    2016-09-01

    Little information is available on infant behavioral development outcomes of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Studies performed to date, all of which relied on global developmental assessments, have yielded inconsistent findings with regard to psychomotor development, negative findings with regard to mental development, and no information as to the development of specific cognitive functions. Our review of these studies leads us to suspect that the use of global developmental assessments might partially explain the negative and inconsistent findings. To identify cognitive processes that might be sensitive to prenatal iodine supplementation, we examined the timing of thyroid hormone action on specific brain systems. The development of infant visual attention is sensitive to thyroid hormone during the early prenatal period, when the fetus is entirely dependent on maternal thyroid hormone. For this reason, infant visual attention has the potential to be a sensitive measure of infant outcomes in prenatal iodine supplementation studies. We suggest the assessment of infant visual attention, with follow-up examination of childhood executive functions, as a means of capturing the effects of maternal iodine deficiency and prenatal iodine supplementation on specific cognitive processes. In particular, we propose comparison of infant performance on global developmental tests and specialized tests of visual attention in pilot trials of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Only by comparing the 2 types of tests side by side will it be possible to establish whether the use of a sensitive measure of infant visual attention will increase the reliability of such supplementation studies. Recognizing that exposure misclassification may also provide a partial explanation for the inconsistent neurodevelopmental outcomes in previous studies, we suggest that urinary iodine concentration or

  14. Methionine sulfoxide reductase A deficiency exacerbates progression of kidney fibrosis induced by unilateral ureteral obstruction.

    PubMed

    Kim, Jee In; Noh, Mi Ra; Kim, Ki Young; Jang, Hee-Seong; Kim, Hwa-Young; Park, Kwon Moo

    2015-12-01

    Methionine sulfoxide reductase A (MsrA), which stereospecifically catalyzes the reduction of methionine-S-sulfoxide, is an important reactive oxygen species (ROS) scavenger. Tissue fibrosis is a maladaptive repair process following injury, associated with oxidative stress. In this study, we investigated the role of MsrA in unilateral ureteral obstruction (UUO)-induced kidney fibrosis and its underlying mechanisms by using MsrA gene-deleted mice (MsrA(-/-)). MsrA deletion increased collagen deposition in the interstitium and the expression of collagen III and α-smooth muscle actin in the UUO kidneys, indicating that MsrA deficiency exacerbated the progression of UUO-induced kidney fibrosis. UUO reduced the kidney expression of MsrA, MsrB1, and MsrB2, thereby decreasing MsrA and MsrB activity. UUO increased hydrogen peroxide and lipid peroxidation levels and the ratio of oxidized glutathione (GSSG) to total glutathione (GSH) in the kidneys. The UUO-induced elevations in the levels of these oxidative stress markers and leukocyte markers were much higher in the MsrA(-/-) than in the MsrA(+/+) kidneys, the latter suggesting that the exacerbated kidney fibrosis in MsrA(-/-) mice was associated with enhanced inflammatory responses. Collectively, our data suggest that MsrA plays a protective role in the progression of UUO-induced kidney fibrosis via suppression of fibrotic responses caused by oxidative stress and inflammation.

  15. Mitochondrial Contagion Induced by Parkin Deficiency in Drosophila Hearts and Its Containment by Suppressing Mitofusin

    PubMed Central

    Bhandari, Poonam; Song, Moshi; Chen, Yun; Burelle, Yan; Dorn, Gerald W.

    2015-01-01

    Rationale Dysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and a potential genetic mechanism of cardiomyopathy. Despite epidemiological associations between Parkinson disease and heart failure, the role of Parkin and mitophagic quality control in maintaining normal cardiac homeostasis is poorly understood. Objective We used germline mutants and cardiac-specific RNA interference to interrogate Parkin regulation of cardiomyocyte mitochondria and examine functional crosstalk between mitophagy and mitochondrial dynamics in Drosophila heart tubes. Methods and Results Transcriptional profiling of Parkin knockout mouse hearts revealed compensatory upregulation of multiple related E3 ubiquitin ligases. Because Drosophila lack most of these redundant genes, we examined heart tubes of parkin knockout flies and observed accumulation of enlarged hollow donut mitochondria with dilated cardiomyopathy, which could be rescued by cardiomyocyte-specific Parkin expression. Identical abnormalities were induced by cardiomyocyte-specific Parkin suppression using 2 different inhibitory RNAs. Parkin-deficient cardiomyocyte mitochondria exhibited dysmorphology, depolarization, and reactive oxygen species generation without calcium cycling abnormalities, pointing to a primary mitochondrial defect. Suppressing cardiomyocyte mitochondrial fusion in Parkin-deficient fly heart tubes completely prevented the cardiomyopathy and corrected mitochondrial dysfunction without normalizing mitochondrial dysmorphology, demonstrating a central role for mitochondrial fusion in the cardiomyopathy provoked by impaired mitophagy. Conclusions Parkin deficiency and resulting mitophagic disruption produces cardiomyopathy in part by contamination of the cardiomyocyte mitochondrial pool through fusion between improperly retained dysfunctional/senescent and normal mitochondria. Limiting mitochondrial contagion by

  16. A review of the iodine status of UK pregnant women and its implications for the offspring

    PubMed Central

    Bath, Sarah C.; Rayman, Margaret P.

    2015-01-01

    Iodine, as a component of the thyroid hormones, is crucial for brain development and is therefore especially important during pregnancy when the brain is developing most rapidly. While randomised controlled trials of pregnant women in regions of severe iodine deficiency have shown that prenatal iodine deficiency causes impaired cognition, less is known of the effects in regions of mild deficiency. This is relevant to the UK as the World Health Organisation now classifies the UK as mildly iodine deficient, based on a national study of 14-15 year old schoolgirls in 2011. We have previously published a study, using samples and data from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC) that found an association between low iodine status in early pregnancy (urinary iodine-to-creatinine ratio < 150 μg/g) and lower verbal IQ and reading scores in the offspring. Though the women in ALSPAC were recruited in the early 1990s, the results of the study are still relevant as their iodine status was similar to that reported in recent studies of UK pregnant women. This review discusses the evidence that mild-to-moderate iodine deficiency during pregnancy has deleterious effects on child neurodevelopment and relates that evidence to the data on iodine status in the UK. It has highlighted a need for nationwide data on iodine status of pregnant women and that a randomised controlled trial of iodine supplementation in pregnant women in a region of mild-to-moderate iodine deficiency with child outcomes as the primary endpoint is required. PMID:25663363

  17. A review of the iodine status of UK pregnant women and its implications for the offspring.

    PubMed

    Bath, Sarah C; Rayman, Margaret P

    2015-08-01

    Iodine, as a component of the thyroid hormones, is crucial for brain development and is therefore especially important during pregnancy when the brain is developing most rapidly. While randomised controlled trials of pregnant women in regions of severe iodine deficiency have shown that prenatal iodine deficiency causes impaired cognition, less is known of the effects in regions of mild deficiency. This is relevant to the UK as the World Health Organisation now classifies the UK as mildly iodine deficient, based on a national study of 14-15 year old schoolgirls in 2011. We have previously published a study using samples and data from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC) that found an association between low iodine status in early pregnancy (urinary iodine-to-creatinine ratio <150 μg/g) and lower verbal IQ and reading scores in the offspring. Though the women in ALSPAC were recruited in the early 1990s, the results of the study are still relevant as their iodine status was similar to that reported in recent studies of UK pregnant women. This review discusses the evidence that mild-to-moderate iodine deficiency during pregnancy has deleterious effects on child neurodevelopment and relates that evidence to the data on iodine status in the UK. It has highlighted a need for nationwide data on iodine status of pregnant women and that a randomised controlled trial of iodine supplementation in pregnant women in a region of mild-to-moderate iodine deficiency with child outcomes as the primary endpoint is required. PMID:25663363

  18. A review of the iodine status of UK pregnant women and its implications for the offspring.

    PubMed

    Bath, Sarah C; Rayman, Margaret P

    2015-08-01

    Iodine, as a component of the thyroid hormones, is crucial for brain development and is therefore especially important during pregnancy when the brain is developing most rapidly. While randomised controlled trials of pregnant women in regions of severe iodine deficiency have shown that prenatal iodine deficiency causes impaired cognition, less is known of the effects in regions of mild deficiency. This is relevant to the UK as the World Health Organisation now classifies the UK as mildly iodine deficient, based on a national study of 14-15 year old schoolgirls in 2011. We have previously published a study using samples and data from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC) that found an association between low iodine status in early pregnancy (urinary iodine-to-creatinine ratio <150 μg/g) and lower verbal IQ and reading scores in the offspring. Though the women in ALSPAC were recruited in the early 1990s, the results of the study are still relevant as their iodine status was similar to that reported in recent studies of UK pregnant women. This review discusses the evidence that mild-to-moderate iodine deficiency during pregnancy has deleterious effects on child neurodevelopment and relates that evidence to the data on iodine status in the UK. It has highlighted a need for nationwide data on iodine status of pregnant women and that a randomised controlled trial of iodine supplementation in pregnant women in a region of mild-to-moderate iodine deficiency with child outcomes as the primary endpoint is required.

  19. Diminished pheromone-induced sexual behavior in neurokinin-1 receptor deficient (TACR1(-/-)) mice.

    PubMed

    Berger, A; Tran, A H; Dida, J; Minkin, S; Gerard, N P; Yeomans, J; Paige, C J

    2012-07-01

    Studies in mice with targeted deletions of tachykinin genes suggest that tachykinins and their receptors influence emotional behaviors such as aggression, depression and anxiety. Here, we investigated whether TAC1- and TAC4-encoded peptides (substance P and hemokinin-1, respectively) and the neurokinin-1 receptor (NK-1R) are involved in the modulation of sexual behaviors. Male mice deficient for the NK-1R (TACR1 (-/-)) exhibited decreased exploration of female urine in contrast to C57BL/6 control mice and mice deficient for NK-1R ligands such as TAC1 (-/-), TAC4 (-/-) and the newly generated TAC1 (-/-) /TAC4 (-/-) mice. In comparison to C57BL/6 mice, mounting frequency and duration were decreased in male TACR1 (-/-) mice, while mounting latency was increased. Decreased preference for sexual pheromones was also seen in female TACR1 (-/-) mice. Furthermore, administration of the NK-1R-antagonist L-703,606 decreased investigation of female urine by male C57BL/6 mice, suggesting an involvement of NK-1R in urine sniffing behavior. Our results provide evidence for the NK-1R in facilitating sexual approach behavior, as male TACR1 (-/-) mice exhibited blunted approach behavior toward females following the initial interaction compared with C57BL/6 mice. NK-1R signaling may therefore play an important role in pheromone-induced sexual behavior.

  20. Inflammation and increased IDO in hippocampus contribute to depression-like behavior induced by estrogen deficiency.

    PubMed

    Xu, Yongjun; Sheng, Hui; Tang, Zhiping; Lu, Jianqiang; Ni, Xin

    2015-07-15

    Estrogen deficiency is involved in the development of depression. However, the mechanism underlying estrogen modulates depression-like behavior remains largely unknown. Inflammation and indoleamine-2,3-dioxygenase (IDO) have been shown to play pivotal roles in various depression models. The objective of the present study was to investigate whether estrogen deficiency-induced depression-like behavior is associated with inflammation and IDO activation in brain. The results showed that ovariectomy resulted in depression-like behavior in female rats and caused a decrease in 5-HT content and an increase in levels of IDO, IFN-γ, IL-6, toll like receptor (TLR)-4 and phosphorylated NF-κB (p65 subunit) in hippocampus but not in prefrontal cortex (PFC). 17β-Estradiol (E2) treatment ameliorated depression-like behavior and restored above neurochemical alternations in hippocampus in ovariectomized rats. Partial correlation analysis showed that the levels of phosphorylated p65, IFN-γ and IL-6 in hippocampus correlated to serum E2 level. Our study suggests that estrogen inhibits inflammation and activates of IDO and maintains 5-HT level in hippocampus, thereby ameliorating depression-like behavior.

  1. Induced polarized state in intentionally grown oxygen deficient KTaO{sub 3} thin films

    SciTech Connect

    Mota, D. A.; Romaguera-Barcelay, Y.; Tkach, A.; Agostinho Moreira, J.; Almeida, A.; Perez de la Cruz, J.; Vilarinho, P. M.; Tavares, P. B.

    2013-07-21

    Deliberately oxygen deficient potassium tantalate thin films were grown by RF magnetron sputtering on Si/SiO{sub 2}/Ti/Pt substrates. Once they were structurally characterized, the effect of oxygen vacancies on their electric properties was addressed by measuring leakage currents, dielectric constant, electric polarization, and thermally stimulated depolarization currents. By using K{sub 2}O rich KTaO{sub 3} targets and specific deposition conditions, KTaO{sub 3-{delta}} oxygen deficient thin films with a K/Ta = 1 ratio were obtained. Room temperature X-ray diffraction patterns show that KTaO{sub 3-{delta}} thin films are under a compressive strain of 2.3% relative to KTaO{sub 3} crystals. Leakage current results reveal the presence of a conductive mechanism, following the Poole-Frenkel formalism. Furthermore, dielectric, polarization, and depolarization current measurements yield the existence of a polarized state below T{sub pol} {approx} 367 Degree-Sign C. A Cole-Cole dipolar relaxation was also ascertained apparently due to oxygen vacancies induced dipoles. After thermal annealing the films in an oxygen atmosphere at a temperature above T{sub pol}, the aforementioned polarized state is suppressed, associated with a drastic oxygen vacancies reduction emerging from annealing process.

  2. Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells

    PubMed Central

    Schiavone, Davide; Guilbaud, Guillaume; Murat, Pierre; Papadopoulou, Charikleia; Sarkies, Peter; Prioleau, Marie-Noëlle; Balasubramanian, Shankar; Sale, Julian E

    2014-01-01

    REV1-deficient chicken DT40 cells are compromised in replicating G quadruplex (G4)-forming DNA. This results in localised, stochastic loss of parental chromatin marks and changes in gene expression. We previously proposed that this epigenetic instability arises from G4-induced replication fork stalls disrupting the accurate propagation of chromatin structure through replication. Here, we test this model by showing that a single G4 motif is responsible for the epigenetic instability of the BU-1 locus in REV1-deficient cells, despite its location 3.5 kb from the transcription start site (TSS). The effect of the G4 is dependent on it residing on the leading strand template, but is independent of its in vitro thermal stability. Moving the motif to more than 4 kb from the TSS stabilises expression of the gene. However, loss of histone modifications (H3K4me3 and H3K9/14ac) around the transcription start site correlates with the position of the G4 motif, expression being lost only when the promoter is affected. This supports the idea that processive replication is required to maintain the histone modification pattern and full transcription of this model locus. PMID:25190518

  3. Reduced inotropic heart response in selenium-deficient mice relates with inducible nitric oxide synthase.

    PubMed

    Gomez, Ricardo M; Levander, Orville A; Sterin-Borda, Leonor

    2003-02-01

    Atria from mice fed a selenium-deficient (Se(-)) diet have a diminished beta-adrenoceptor-inotropic cardiac response to isoproterenol or norepinephrine compared with atria from mice fed the same diet supplemented with 0.2 mg/kg Se as sodium selenite (Se(+)). This diminished response could be reversed by feeding Se(-) mice the Se(+) diet for 1 wk or by pretreatment with nitric oxide synthase (NOS) inhibitors such as N(G)-monomethyl-l-arginine or aminopyridine. Elevated serum concentrations of nitrite/nitrate as well as a threefold increase in the atrial NOS activity were seen in the Se(-) versus Se(+) mice. Western blotting and indirect immunofluorescence indicated an enhanced expression of inducible NOS in hearts from Se(-) mice. Increased expression and activity of NOS and increased nitrite/nitrate levels from Se(-) mice correlated with an impaired response to beta-adrenoceptor inotropic cardiac stimulation. Elevated nitric oxide levels may account for some of the pathophysiological effects of Se deficiency on the heart. PMID:12529255

  4. Triplex structures induce DNA double strand breaks via replication fork collapse in NER deficient cells

    PubMed Central

    Kaushik Tiwari, Meetu; Adaku, Nneoma; Peart, Natoya; Rogers, Faye A.

    2016-01-01

    Structural alterations in DNA can serve as natural impediments to replication fork stability and progression, resulting in DNA damage and genomic instability. Naturally occurring polypurine mirror repeat sequences in the human genome can create endogenous triplex structures evoking a robust DNA damage response. Failures to recognize or adequately process these genomic lesions can result in loss of genomic integrity. Nucleotide excision repair (NER) proteins have been found to play a prominent role in the recognition and repair of triplex structures. We demonstrate using triplex-forming oligonucleotides that chromosomal triplexes perturb DNA replication fork progression, eventually resulting in fork collapse and the induction of double strand breaks (DSBs). We find that cells deficient in the NER damage recognition proteins, XPA and XPC, accumulate more DSBs in response to chromosomal triplex formation than NER-proficient cells. Furthermore, we demonstrate that XPC-deficient cells are particularly prone to replication-associated DSBs in the presence of triplexes. In the absence of XPA or XPC, deleterious consequences of triplex-induced genomic instability may be averted by activating apoptosis via dual phosphorylation of the H2AX protein. Our results reveal that damage recognition by XPC and XPA is critical to maintaining replication fork integrity and preventing replication fork collapse in the presence of triplex structures. PMID:27298253

  5. Geographical distribution of drinking-water with high iodine level and association between high iodine level in drinking-water and goitre: a Chinese national investigation.

    PubMed

    Shen, Hongmei; Liu, Shoujun; Sun, Dianjun; Zhang, Shubin; Su, Xiaohui; Shen, Yanfeng; Han, Hepeng

    2011-07-01

    Excessive iodine intake can cause thyroid function disorders as can be caused by iodine deficiency. There are many people residing in areas with high iodine levels in drinking-water in China. The main aim of the present study was to map the geographical distribution of drinking-water with high iodine level in China and to determine the relationship between high iodine level in drinking-water and goitre prevalence. Iodine in drinking-water was measured in 1978 towns of eleven provinces in China, with a total of 28,857 water samples. We randomly selected children of 8-10 years old, examined the presence of goitre and measured their urinary iodine in 299 towns of nine provinces. Of the 1978 towns studied, 488 had iodine levels between 150 and 300 μg/l in drinking-water, and in 246 towns, the iodine level was >300 μg/l. These towns are mainly distributed along the original Yellow River flood areas, the second largest river in China. Of the 56 751 children examined, goitre prevalence was 6.3 % in the areas with drinking-water iodine levels of 150-300 μg/l and 11.0 % in the areas with drinking-water iodine >300 μg/l. Goitre prevalence increased with water and urinary iodine levels. For children with urinary iodine >1500 μg/l, goitre prevalence was 3.69 times higher than that for those with urinary iodine levels of 100-199 μg/l. The present study suggests that drinking-water with high iodine levels is distributed in eleven provinces of China. Goitre becomes more prevalent with the increase in iodine level in drinking-water. Therefore, it becomes important to prevent goitre through stopping the provision of iodised salt and providing normal drinking-water iodine through pipelines in these areas in China.

  6. Parameters of an electric-discharge generator of iodine atoms for a chemical oxygen-iodine laser

    SciTech Connect

    Azyazov, V N; Vorob'ev, M V; Voronov, A I; Kupryaev, Nikolai V; Mikheev, P A; Ufimtsev, N I

    2009-01-31

    Laser-induced fluorescence is used for measuring the concentration of iodine molecules at the output of an electric-discharge generator of atomic iodine. Methyl iodide CH{sub 3}I is used as the donor of atomic iodine. The fraction of iodine extracted from CH{sub 3}I in the generator is {approx}50%. The optimal operation regimes are found in which 80%-90% of iodine contained in the output flow of the generator was in the atomic state. This fraction decreased during the iodine transport due to recombination and was 20%-30% at the place where iodine was injected into the oxygen flow. The fraction of the discharge power spent for dissociation was {approx}3%. (elements of laser setups)

  7. Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis.

    PubMed

    Ryz, Natasha R; Lochner, Arion; Bhullar, Kirandeep; Ma, Caixia; Huang, Tina; Bhinder, Ganive; Bosman, Else; Wu, Xiujuan; Innis, Sheila M; Jacobson, Kevan; Vallance, Bruce A

    2015-11-01

    Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1β, IL-6, TGF-β, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.

  8. Trace element deficiencies and fertility in ruminants: a review.

    PubMed

    Hidiroglou, M

    1979-08-01

    Various minerals (copper, cobalt, selenium, manganese, iodine, zinc, and iron) can influence reproductive performance of ruminants. Reproductive failure may be induced by deficiencies of single or combined trace elements and by imbalances. This review is focused on maladjustments of trace elements leading to impaired breeding performance. Opinion is diverse as to the existence of various reproductive disturbances from either a severe copper depletion or a marginal dietary copper deficiency. Field experience suggests that administration of cobalt to ruminants on cobalt-deficient diets improves their impaired breeding performance. Selenium infertility in ewes is more prevalent in some areas and in some seasons, but the actual cause of this malady and the continuing role of additional factors are unknown. Manganese is necessary for normal fertility in ruminants, and feeding low-manganese rations depresses conception rates. Lack of iodine impairs thyroid activity and also ovarian function. Reproductive failure in the female and in spermatogenesis are manifestations of zinc deficiency. Despite forages rich in iron, low availability in certain instances could affect adversely ruminant reproduction. Knowledge of biochemical dysfunctions from trace element deficiencies is essential to determine the role which trace elements play in fertility of ruminant animals.

  9. Iodine intake and status of UK women of childbearing age recruited at the University of Surrey in the winter

    PubMed Central

    Bath, Sarah C.; Sleeth, Michelle L.; McKenna, Marianne; Walter, Alan; Taylor, Andrew; Rayman, Margaret P.

    2015-01-01

    As intra-thyroidal iodine stores should be maximised before conception to facilitate the increased thyroid-hormone production of pregnancy, women who may become pregnant should ideally consume 150 μg iodine/day [US Recommended Dietary Allowance (RDA)]. As few UK data exist in this population group, our aim was to assess iodine intake and status in women of childbearing age in a cross-sectional study at the University of Surrey. Total iodine excretion was measured from 24-h urine samples in 57 women; iodine intake was estimated by assuming that 90% of ingested iodine was excreted. Average iodine intake was also estimated from 48-h food diaries that the women completed. The median urinary-iodine concentration (63.1 μg/L) classified the group as mildly iodine deficient by WHO criteria. By contrast, the median 24-h iodine excretion (149.8 μg/24-h), suggested a relatively low risk of iodine deficiency. Median estimated iodine intake, extrapolated from urinary excretion, was 167 μg/day, whereas it was lower, at 123 μg/day, when estimated from the 48-h food-diaries. Iodine intake from food diaries and 24-h iodine excretion were strongly correlated (r=0.75, p<0.001). Intake of milk, eggs and dairy products was positively associated with iodine status. The iodine status of this UK cohort is probably a best-case scenario as the women were mostly nutrition students and were recruited in the winter when milk-iodine content is at its highest; further study in more representative cohorts of UK women is required. Our study highlights a need for revised cut-offs for iodine deficiency that are method- and age-group specific. PMID:25274294

  10. Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway

    PubMed Central

    Tongqiang, Liu; Shaopeng, Liu; Xiaofang, Yu; Nana, Song; Xialian, Xu; Jiachang, Hu; Ting, Zhang; Xiaoqiang, Ding

    2016-01-01

    Contrast-induced acute renal injury (CI-AKI) has become a common cause of hospital-acquired renal failure. However, the development of prophylaxis strategies and approved therapies for CI-AKI is limited. Salvianolic acid B (SB) can treat cardiovascular-related diseases. The aim of the present study was to assess the effect of SB on prevention of CI-AKI and explore its underlying mechanisms. We examined its effectiveness of preventing renal injury in a novel CI-AKI rat model. Compared with saline, intravenous SB pretreatment significantly attenuated elevations in serum creatinine and the histological changes of renal tubular injuries, reduced the number of apoptosis-positive tubular cells, activated Nrf2, and lowered the levels of renal oxidative stress induced by iodinated contrast media. The above renoprotection of SB was abolished by the PI3K inhibitor (wortmannin). In HK-2 cells, SB activated Nrf2 and decreased the levels of oxidative stress induced by hydrogen peroxide and subsequently improved cell viability. The above cytoprotection of SB was blocked by the PI3K inhibitor (wortmannin) or siNrf2. Thus, our results demonstrate that, due to its antioxidant properties, SB has the potential to effectively prevent CI-AKI via the PI3K/Akt/Nrf2 pathway. PMID:27382429

  11. Nitrous oxide-induced B₁₂ deficiency myelopathy: Perspectives on the clinical biochemistry of vitamin B₁₂.

    PubMed

    Hathout, Leith; El-Saden, Suzie

    2011-02-15

    Beginning with a case report of nitrous oxide (N₂O)-induced B₁₂ deficiency myelopathy, this article reviews the clinical biochemistry of vitamin B₁₂, and examines the pathogenetic mechanisms by which B₁₂ deficiency leads to neurologic damage, and how this damage is potentiated by N₂O exposure. The article systematically examines the available experimental data relating to the two main coenzyme mechanisms that are usually suggested in clinical articles, particularly the deficient methylation hypothesis. The article demonstrates that neither of these mechanisms is fully consistent with the available data. The article then presents a novel mechanism based on new data from the neuroimmunology basic science literature which suggests that the pathogenesis of B₁₂ deficiency myelopathy may not be related to its role as a coenzyme, but rather to newly discovered functions of B₁₂ in regulating cytokines and growth factors.

  12. Iodine and thyroid hormones during pregnancy and postpartum.

    PubMed

    Pérez-López, Faustino R

    2007-07-01

    Iodine is a trace element essential for synthesis of the thyroid hormones, triiodothyronine and thyroxine. These hormones play a vital role in the early growth and development stages of most organs, especially the brain. The World Health Organization (WHO) has declared that, after famine, iodine deficiency is the most avoidable cause of cerebral lesions including different degrees of mental retardation and cerebral paralysis. The main function of iodine in vertebrates is to interact with the thyroid hormones. During pregnancy sufficient quantities of iodine are required to prevent the appearance of hypothyroidism, trophoblastic and embryonic or fetal disorders, neonatal and maternal hypothyroidism, and permanent sequelae in infants. Thyroid hormone receptors and iodothyronine deiodinases are present in placenta and central nervous tissue of the fetus. A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake in a population have profound effects on the occurrence of thyroid abnormalities. The prevalence of disorders related to iodine deficit during pregnancy and postpartum has increased. Iodine supplementation is an effective measure in the case of pregnant and lactating women. However, it is not implemented and the problem is still present even in societies with theoretically advanced health systems. During pregnancy and postpartum, the WHO recommends iodine intake be increased to at least 200 microg/day. Side-effects provoked by iodine supplementation are rare during pregnancy at the recommended doses. PMID:17701774

  13. Mas receptor deficiency exacerbates lipopolysaccharide-induced cerebral and systemic inflammation in mice.

    PubMed

    Oliveira-Lima, Onésia C; Pinto, Mauro C X; Duchene, Johan; Qadri, Fatimunnisa; Souza, Laura L; Alenina, Natalia; Bader, Michael; Santos, Robson A S; Carvalho-Tavares, Juliana

    2015-12-01

    Beyond the classical actions of the renin-angiotensin system on the regulation of cardiovascular homeostasis, several studies have shown its involvement in acute and chronic inflammation. The G protein-coupled receptor Mas is a functional binding site for the angiotensin-(1-7); however, its role in the immune system has not been fully elucidated. In this study, we evaluated the effect of genetic deletion of Mas receptor in lipopolysaccharide (LPS)-induced systemic and cerebral inflammation in mice. Inflammatory response was triggered in Mas deficient (Mas(-/-)) and C57BL/6 wild-type (WT) mice (8-12 weeks-old) by intraperitoneal injection of LPS (5 mg/kg). Mas(-/-) mice presented more intense hypothermia compared to WT mice 24 h after LPS injection. Systemically, the bone marrow of Mas(-/-) mice contained a lower number of neutrophils and monocytes 3 h and 24 h after LPS injection, respectively. The plasma levels of inflammatory mediators KC, MCP-1 and IL-10 were higher in Mas(-/-) mice 24 h after LPS injection in comparison to WT. In the brain, Mas(-/-) animals had a significant increase in the number of adherent leukocytes to the brain microvasculature compared to WT mice, as well as, increased number of monocytes and neutrophils recruited to the pia-mater. The elevated number of adherent leukocytes on brain microvasculature in Mas(-/-) mice was associated with increased expression of CD11b - the alpha-subunit of the Mac-1 integrin - in bone marrow neutrophils 3h after LPS injection, and with increased brain levels of chemoattractants KC, MIP-2 and MCP-1, 24 h later. In conclusion, we demonstrated that Mas receptor deficiency results in exacerbated inflammation in LPS-challenged mice, which suggest a potential role for the Mas receptor as a regulator of systemic and brain inflammatory response induced by LPS.

  14. Mixed chimerism and transplant tolerance are not effectively induced in C3a-deficient mice.

    PubMed

    Baśkiewicz-Hałasa, Magdalena; Rogińska, Dorota; Piecyk, Katarzyna; Hałasa, Maciej; Lejkowska, Renata; Pius-Sadowska, Ewa; Machaliński, Bogusław

    2015-01-01

    Mixed chimerism, a phenomenon involved in the development of specific alloantigen tolerance, could be achieved through the transplantation of hematopoietic stem cells into properly prepared recipients. Because the C3a complement component modulates hematopoietic cell trafficking after transplantation, in the present study, we investigated the influence of the C3a deficiency on mixed chimerism and alloantigen tolerance induction. To induce mixed chimerism, C57BL/6J (wild-type strain; H-2K(b); I-E(-)) and B6.129S4-C3(tm1Crr)/J (C3a-deficient) mice were exposed to 3 G total body irradiation (day -1). Subsequently, these mice were treated with CD8-blocking (day -2) and CD40L-blocking (days 0 and 4) antibodies, followed by transplantation with 20 × 10(6) Balb/c (H-2K(d); I-E(+)) bone marrow cells (day 0). The degree of mixed chimerism in peripheral blood leukocytes was measured several times during the 20-week experiment. The tolerance to Balb/c mouse antigens was assessed based on the number of lymphocytes expressing Vβ5 and Vβ11 T-cell receptor and on skin-graft (day 0) acceptance. Applying our experimental model, mixed chimerism and alloantigen tolerance were effectively induced in C57BL/6J (wild-type) mice, but not in C3a(-/-) animals. The present study is, to our knowledge, the first to demonstrate that C3a is vital for achieving stable mixed chimerism and related to this induction of transplant tolerance.

  15. Deficiency of phospholipase A2 receptor exacerbates ovalbumin-induced lung inflammation.

    PubMed

    Tamaru, Shun; Mishina, Hideto; Watanabe, Yosuke; Watanabe, Kazuhiro; Fujioka, Daisuke; Takahashi, Soichiro; Suzuki, Koji; Nakamura, Takamitsu; Obata, Jun-Ei; Kawabata, Kenichi; Yokota, Yasunori; Murakami, Makoto; Hanasaki, Kohji; Kugiyama, Kiyotaka

    2013-08-01

    Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R(-/-)) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R(+/+)) mice, PLA2R(-/-) mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R(-/-) mice, intratracheally instilled [(125)I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R(+/+) mice. The degradation of the instilled [(125)I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R(-/-) mice than in PLA2R(+/+) mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.

  16. Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

    PubMed

    Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

    2015-08-01

    Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD). PMID:25592072

  17. Cnr2 deficiency confers resistance to inflammation-induced preterm birth in mice.

    PubMed

    Sun, Xiaofei; Cappelletti, Monica; Li, Yingju; Karp, Christopher L; Divanovic, Senad; Dey, Sudhansu K

    2014-10-01

    Infection-induced inflammation, frequently associated with increased production of proinflammatory cytokines, is considered a significant contributor to preterm birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is expressed in various immune cells and was shown to modulate immune responses. We show here that Cnr2, but not Cnr1, deficient mice are resistant to lipopolysaccharide (LPS)-driven preterm birth and suppression of serum progesterone levels. After LPS challenge, Cnr2(-/-) mice exhibited increased serum levels of IL-10 with decreased IL-6 levels. These changes were associated with reduced LPS-induced Ptgs2 expression at the maternal-conceptus interface on day 16 of pregnancy. LPS stimulation of Cnr2(-/-) dendritic cells in vitro resulted in increased IL-10 with reduced IL-6 production and correlated with increased cAMP accumulation. Collectively, our results suggest that increased IL-10 production occurring via augmented cAMP accumulation represents a potential mechanism for the resistance of Cnr2(-/-) mice to LPS-induced preterm birth. These results may have clinical relevance, because currently, there are limited options to prevent preterm birth. PMID:25051450

  18. dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development.

    PubMed

    Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-02-01

    Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis.

  19. Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity.

    PubMed

    Hartmann, Phillipp; Seebauer, Caroline T; Mazagova, Magdalena; Horvath, Angela; Wang, Lirui; Llorente, Cristina; Varki, Nissi M; Brandl, Katharina; Ho, Samuel B; Schnabl, Bernd

    2016-03-01

    Nonalcoholic fatty liver disease (NAFLD) and obesity are characterized by altered gut microbiota, inflammation, and gut barrier dysfunction. Here, we investigated the role of mucin-2 (Muc2) as the major component of the intestinal mucus layer in the development of fatty liver disease and obesity. We studied experimental fatty liver disease and obesity induced by feeding wild-type and Muc2-knockout mice a high-fat diet (HFD) for 16 wk. Muc2 deficiency protected mice from HFD-induced fatty liver disease and obesity. Compared with wild-type mice, after a 16-wk HFD, Muc2-knockout mice exhibited better glucose homeostasis, reduced inflammation, and upregulated expression of genes involved in lipolysis and fatty acid β-oxidation in white adipose tissue. Compared with wild-type mice that were fed the HFD as well, Muc2-knockout mice also displayed higher intestinal and plasma levels of IL-22 and higher intestinal levels of the IL-22 target genes Reg3b and Reg3g. Our findings indicate that absence of the intestinal mucus layer activates the mucosal immune system. Higher IL-22 levels protect mice from diet-induced features of the metabolic syndrome.

  20. Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

    PubMed

    Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

    2015-08-01

    Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD).

  1. Sphingosine Kinase 1 Deficiency Confers Protection against Hyperoxia-Induced Bronchopulmonary Dysplasia in a Murine Model

    PubMed Central

    Harijith, Anantha; Pendyala, Srikanth; Reddy, Narsa M.; Bai, Tao; Usatyuk, Peter V.; Berdyshev, Evgeny; Gorshkova, Irina; Huang, Long Shuang; Mohan, Vijay; Garzon, Steve; Kanteti, Prasad; Reddy, Sekhar P.; Raj, J. Usha; Natarajan, Viswanathan

    2014-01-01

    Bronchopulmonary dysplasia of the premature newborn is characterized by lung injury, resulting in alveolar simplification and reduced pulmonary function. Exposure of neonatal mice to hyperoxia enhanced sphingosine-1-phosphate (S1P) levels in lung tissues; however, the role of increased S1P in the pathobiological characteristics of bronchopulmonary dysplasia has not been investigated. We hypothesized that an altered S1P signaling axis, in part, is responsible for neonatal lung injury leading to bronchopulmonary dysplasia. To validate this hypothesis, newborn wild-type, sphingosine kinase1−/− (Sphk1−/−), sphingosine kinase 2−/− (Sphk2−/−), and S1P lyase+/− (Sgpl1+/−) mice were exposed to hyperoxia (75%) from postnatal day 1 to 7. Sphk1−/−, but not Sphk2−/− or Sgpl1+/−, mice offered protection against hyperoxia-induced lung injury, with improved alveolarization and alveolar integrity compared with wild type. Furthermore, SphK1 deficiency attenuated hyperoxia-induced accumulation of IL-6 in bronchoalveolar lavage fluids and NADPH oxidase (NOX) 2 and NOX4 protein expression in lung tissue. In vitro experiments using human lung microvascular endothelial cells showed that exogenous S1P stimulated intracellular reactive oxygen species (ROS) generation, whereas SphK1 siRNA, or inhibitor against SphK1, attenuated hyperoxia-induced S1P generation. Knockdown of NOX2 and NOX4, using specific siRNA, reduced both basal and S1P-induced ROS formation. These results suggest an important role for SphK1-mediated S1P signaling–regulated ROS in the development of hyperoxia-induced lung injury in a murine neonatal model of bronchopulmonary dysplasia. PMID:23933064

  2. Selenium and Iodine in Autoimmune Thyroiditis.

    PubMed

    Guastamacchia, Edoardo; Giagulli, Vito Angelo; Licchelli, Brunella; Triggiani, Vincenzo

    2015-01-01

    Selenium and iodine are essential for thyroid hormone synthesis and function. Selenium, in form of selenocysteine, is found either in the catalytic center of enzymes involved in the protection of the thyroid gland from free radicals originating during thyroid hormone synthesis, and in three different iodothyronine deiodinases catalyzing the activation and the inactivation of thyroid hormones. Iodine is an essential constituent of thyroid hormones and its deficiency causes different disorders that include goiter, hypothyroidism, reduced fertility and alteration in growth, physical and neurological development. These two micronutrients could be involved in the pathogenesis of autoimmune thyroid diseases, a spectrum of pathological conditions including Hashimoto's thryoiditis, post-partum thyroiditis, the so-called painless thyroiditis, Graves' disease and Graves' ophtalmopathy. Aim of this paper is to review the role played by selenium and iodine in autoimmune thyroiditis.

  3. Iodine intake and status during pregnancy and lactation before and after government initiatives to improve iodine status, in Palmerston North, New Zealand: a pilot study.

    PubMed

    Brough, Louise; Jin, Ying; Shukri, Nurul Husna; Wharemate, Zirsha Roimata; Weber, Janet L; Coad, Jane

    2015-10-01

    Iodine deficiency during pregnancy and lactation may adversely affect fetal and infant development. Two initiatives were introduced in New Zealand to prevent deficiency: (1) mandatory fortification of bread with iodised salt; and (2) provision of a subsidised iodine supplement (150 μg) for all pregnant and breastfeeding women. The aim of this study was to assess iodine intake and status among a self-selecting sample of pregnant and lactating women in Palmerston North, both before and after the two initiatives. Pregnant and breastfeeding women were recruited before (n = 25 and 32; 2009) and after (n = 34 and 36; 2011) the initiatives. Iodine concentration was determined in 24-h urine and breast milk samples using inductively-coupled plasma mass spectrometry. Use of supplements and salt, knowledge of iodine deficiency, and awareness of the initiatives were determined by questionnaire. Median urine iodine concentration (UIC) was higher in 2011 compared with 2009 for both pregnant (85 and 47 μg L(-1) ) and breastfeeding (74 and 34 μg L(-1) ) participants; median UIC were below the cut-offs for adequate iodine status. However, in 2011, the estimated daily iodine intake during pregnancy was 217 μg day(-1) ; 74% of women achieved the Estimated Average Requirement. Knowledge of the initiatives was low, only 28-56% were aware of the need for iodine supplements and only 15-22% were aware of the mandatory addition of iodised salt to bread. Despite initiatives, UIC of these women indicates iodine deficiency, however, dietary intakes appear adequate. Ongoing surveillance of supplement use and iodine status among pregnant and lactating women throughout New Zealand is needed to fully assess the efficacy of the initiatives. Alternative strategies may require evaluation to ensure all women have adequate iodine during pregnancy and breastfeeding.

  4. Selenium deficiency and thyroid fibrosis. A key role for macrophages and transforming growth factor beta (TGF-beta).

    PubMed

    Contempre, B; Le Moine, O; Dumont, J E; Denef, J F; Many, M C

    1996-11-29

    Free radical damage and fibrosis caused by selenium deficiency are thought to be involved in the pathogenesis of myxoedematous cretinism. So far, no pathway explains the link between selenium deficiency and tissue fibrosis. Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids. Necrosis is much increased if the glands are also selenium-deficient, which then evolve to fibrosis. This rat model was reproduced to explore the role of selenium deficiency in defective tissue repair. At first, proliferation indexes of epithelial cells and fibroblasts were comparable between selenium-deficient and control groups. Then, in selenium-deficient thyroids the inflammatory reaction was more marked being mainly composed of macrophages. The proliferation index of the epithelial cells decreased, while that of the fibroblasts increased. These thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the proliferation indexes, and blocked the evolution to fibrosis. In selenium deficiency, an active fibrotic process occurs in the thyroid, in which the inflammatory reaction and an excess of TGF-beta play a key role. PMID:9027319

  5. Quantitative mRNA expression analysis of selected genes in patients with early-stage hypothyroidism induced by treatment with iodine-131.

    PubMed

    Guo, Kun; Gao, Rui; Yu, Yan; Zhang, Weixiao; Yang, Yuxuan; Yang, Aimin

    2015-11-01

    The present study aimed to investigate the molecular markers indicative of early-stage hypothyroidism induced by treatment with iodine-131, in order to assist in further investigations of radio iodine‑induced hypothyroidism. A total of 59 patients diagnosed with hyperthyroidism (male/female, 16/43; median age, 46.4 years) and 27 healthy subjects (male/female, 7/21; median age, 44.6 years) were included in the present study. All patients were treated with appropriate doses of iodine‑131 and, three months following treatment, the patients were subdivided into two groups: A group with early‑stage hypothyroidism symptoms, and a group with non‑early‑stage hypothyroidism, including euthyroid patients and patients remaining with hyperthyroidism. Tissue samples from the patients and healthy subjects were collected by fine needle biopsies, and the mRNA expression levels of B-cell lymphoma 2 (Bcl‑2), nuclear factor (NF)‑κB, Ku70, epidermal growth factor receptor (EGFR), early growth response 1 (Egr‑1), TP53 and ataxia telangiectasia mutated were analyzed using reverse transcription‑quantitative polymerase chain reaction prior to iodine‑131 treatment. The association of the variation of target genes with susceptibility to early‑stage hypothyroidism was analyzed. Compared with normal subjects, the mRNA expression levels of Ku70 (0.768, vs. 3.304, respectively; P<0.001) and EGFR (0.859, vs. 1.752, respectively; P<0.05) were significantly higher, whereas those of NF‑κB (0.884, vs. 0.578, respectively; P<0.05) and Bcl‑2 (1.235, vs. 0.834, respectively; P<0.05) were lower in the hyperthyroid patients. Following treatment with iodine‑131, 30 of the 59 (50.8%) patients with hyperthyroidism were diagnosed with early‑stage hypothyroidism, and in the early‑stage hypothyroidism group, the mRNA expression levels of Bcl‑2 were significantly decreased (P<0.05), whereas those of Egr‑1 (P<0.05) were significantly increased, compared with the non

  6. Quantitative mRNA expression analysis of selected genes in patients with early-stage hypothyroidism induced by treatment with iodine-131.

    PubMed

    Guo, Kun; Gao, Rui; Yu, Yan; Zhang, Weixiao; Yang, Yuxuan; Yang, Aimin

    2015-11-01

    The present study aimed to investigate the molecular markers indicative of early-stage hypothyroidism induced by treatment with iodine-131, in order to assist in further investigations of radio iodine‑induced hypothyroidism. A total of 59 patients diagnosed with hyperthyroidism (male/female, 16/43; median age, 46.4 years) and 27 healthy subjects (male/female, 7/21; median age, 44.6 years) were included in the present study. All patients were treated with appropriate doses of iodine‑131 and, three months following treatment, the patients were subdivided into two groups: A group with early‑stage hypothyroidism symptoms, and a group with non‑early‑stage hypothyroidism, including euthyroid patients and patients remaining with hyperthyroidism. Tissue samples from the patients and healthy subjects were collected by fine needle biopsies, and the mRNA expression levels of B-cell lymphoma 2 (Bcl‑2), nuclear factor (NF)‑κB, Ku70, epidermal growth factor receptor (EGFR), early growth response 1 (Egr‑1), TP53 and ataxia telangiectasia mutated were analyzed using reverse transcription‑quantitative polymerase chain reaction prior to iodine‑131 treatment. The association of the variation of target genes with susceptibility to early‑stage hypothyroidism was analyzed. Compared with normal subjects, the mRNA expression levels of Ku70 (0.768, vs. 3.304, respectively; P<0.001) and EGFR (0.859, vs. 1.752, respectively; P<0.05) were significantly higher, whereas those of NF‑κB (0.884, vs. 0.578, respectively; P<0.05) and Bcl‑2 (1.235, vs. 0.834, respectively; P<0.05) were lower in the hyperthyroid patients. Following treatment with iodine‑131, 30 of the 59 (50.8%) patients with hyperthyroidism were diagnosed with early‑stage hypothyroidism, and in the early‑stage hypothyroidism group, the mRNA expression levels of Bcl‑2 were significantly decreased (P<0.05), whereas those of Egr‑1 (P<0.05) were significantly increased, compared with the non

  7. [The structure and phosphorus or potassium deficiency induced expression of a calmodulin-like protein gene in Arabidopsis].

    PubMed

    Duan, Rui-Jun; Yi, Ke-Ke; Wu, Ping

    2005-10-01

    According to our previous microarray analysis, we found a putative calmodulin gene related to Pi deficiency and designated AtPsiCaM (Arabidopsis Pi-starvation-induced CaM). Results of structural analysis indicate that AtPsiCaM has three conserved EF-hands motif and belongs to calmodulin-like proteins family (Figs. 1-3). Northern blot analysis revealed that this gene could be induced by potassium and phosphate deficiency and not by potassium deficiency or high salinity (Fig. 4). The results of RT-PCR and GUS histochemical staining assays of the AtPsiCaM promoter::GUS transgenic plants showed that this gene can be expressed in all tissues to different expression levels (Figs. 5, 6). PMID:16222095

  8. Supplemental iodine as a key to reproduction in pandas?

    PubMed

    Milewski, Antoni V; Dierenfeld, Ellen S

    2012-06-01

    Pandas are endemic to iodine-poor environments and appear to be specialized for a goitrogenic staple diet. In particular, the importance of thiocyanate in bamboos might possibly have been overlooked in captive breeding programs. Although excreted in urine, thiocyanate first antagonizes absorption of iodine by the thyroid (of parent, fetus and suckling juveniles) and the mammary glands. In livestock and humans, subclinical deficiency of iodine is known to result in reproductive problems (including retardation of the fetus and suckling infant) even where the mother appears to be unaffected beyond slight hyperplasia of the thyroid and subtle hypothyroidism as reflected by levels of thyroid hormones. We suggest that the possibilities of iodine deficiency or excess should be carefully considered wherever the reproductive rates of pandas are unsatisfactory. PMID:22691201

  9. Supplemental iodine as a key to reproduction in pandas?

    PubMed

    Milewski, Antoni V; Dierenfeld, Ellen S

    2012-06-01

    Pandas are endemic to iodine-poor environments and appear to be specialized for a goitrogenic staple diet. In particular, the importance of thiocyanate in bamboos might possibly have been overlooked in captive breeding programs. Although excreted in urine, thiocyanate first antagonizes absorption of iodine by the thyroid (of parent, fetus and suckling juveniles) and the mammary glands. In livestock and humans, subclinical deficiency of iodine is known to result in reproductive problems (including retardation of the fetus and suckling infant) even where the mother appears to be unaffected beyond slight hyperplasia of the thyroid and subtle hypothyroidism as reflected by levels of thyroid hormones. We suggest that the possibilities of iodine deficiency or excess should be carefully considered wherever the reproductive rates of pandas are unsatisfactory.

  10. Room-Temperature Fluorine-Induced Decrease in the Stability of Bromine and Iodine Intercalated Carbon Fibers

    NASA Technical Reports Server (NTRS)

    Hung, Ching-Cheh

    1995-01-01

    Upon exposure to room-temperature fluorine, intercalated carbon fibers (containing either bromine alone or iodine and bromine together) become heavier and less stable. For Amoco P-100 graphitized carbon fibers, which were intercalated with 18 wt percent bromine, 1 hour of fluorine exposure resulted in a large weight increase but caused only a small decrease in thermal stability. An additional 89 hours of fluorine exposure time resulted in small additional increases in fiber weight, but significant further decreases in fiber thermal stability. Such phenomena of weight increase and stability decrease do not occur if the intercalated fibers are exposed to 250 C fluorine. These observations suggest that, at room temperature, fluorine is absorbed quickly by the intercalated fibers and is intercalated slowly into the fibers. Most of the original intercalates are replaced by fluorine in the process of fluorine intercalation. In an inert environment, the bromine intercalated fibers are much more thermally stable. After 800 C vacuum heating for 2 weeks, the brominated fibers lost about 45% of their bromine, and their resistivity increased from 64 mu(Omega)-cm to a range of 95-170 mu(Omega)-cm. This is still much lower than the value of 300 mu(Omega)-cm for pristine P-100. For practical purposes, to preserve their thermal stability, brominated fibers need to be protected from exposure to fluorine at room temperature or to any intercalate at a temperature where, upon direct contact with graphite, an intercalation compound can easily be formed.

  11. The Development and Deployment of a Ground-Based, Laser-Induced Fluorescence Instrument for the In Situ Detection of Iodine Monoxide Radicals

    NASA Technical Reports Server (NTRS)

    Thurlow, M. E.; Co, D. T.; O'Brien, A. S.; Hannun, R. A.; Lapson, L. B.; Hanisco, T. F.; Anderson, J. G.

    2014-01-01

    High abundances of iodine monoxide (IO) are known to exist and to participate in local photochemistry of the marine boundary layer. Of particular interest are the roles IO plays in the formation of new particles in coastal marine environments and in depletion episodes of ozone and mercury in the Arctic polar spring. This paper describes a ground-based instrument that measures IO at mixing ratios less than one part in 1012. The IO radical is measured by detecting laser-induced fluorescence at wavelengths longer that 500 nm. Tunable visible light is used to pump the A23/2 (v = 2) ? X23/2 (v = 0) transition of IO near 445 nm. The laser light is produced by a solid-state, Nd:YAG-pumped Ti:Sapphire laser at 5 kHz repetition rate. The laser-induced fluorescence instrument performs reliably with very high signal-to-noise ratios (>10) achieved in short integration times (<1 min). The observations from a validation deployment to the Shoals Marine Lab on Appledore Island, ME are presented and are broadly consistent with in situ observations from European Coastal Sites. Mixing ratios ranged from the instrumental detection limit (<1 pptv) to 10 pptv. These data represent the first in situ point measurements of IO in North America.

  12. The development and deployment of a ground-based, laser-induced fluorescence instrument for the in situ detection of iodine monoxide radicals

    SciTech Connect

    Thurlow, M. E. Hannun, R. A.; Lapson, L. B.; Anderson, J. G.; Co, D. T.; O'Brien, A. S.; Hanisco, T. F.

    2014-04-15

    High abundances of iodine monoxide (IO) are known to exist and to participate in local photochemistry of the marine boundary layer. Of particular interest are the roles IO plays in the formation of new particles in coastal marine environments and in depletion episodes of ozone and mercury in the Arctic polar spring. This paper describes a ground-based instrument that measures IO at mixing ratios less than one part in 10{sup 12}. The IO radical is measured by detecting laser-induced fluorescence at wavelengths longer that 500 nm. Tunable visible light is used to pump the A{sup 2}Π{sub 3/2} (v{sup ′} = 2) ← X{sup 2}Π{sub 3/2} (v{sup ″} = 0) transition of IO near 445 nm. The laser light is produced by a solid-state, Nd:YAG-pumped Ti:Sapphire laser at 5 kHz repetition rate. The laser-induced fluorescence instrument performs reliably with very high signal-to-noise ratios (>10) achieved in short integration times (<1 min). The observations from a validation deployment to the Shoals Marine Lab on Appledore Island, ME are presented and are broadly consistent with in situ observations from European Coastal Sites. Mixing ratios ranged from the instrumental detection limit (<1 pptv) to 10 pptv. These data represent the first in situ point measurements of IO in North America.

  13. The development and deployment of a ground-based, laser-induced fluorescence instrument for the in situ detection of iodine monoxide radicals.

    PubMed

    Thurlow, M E; Co, D T; O'Brien, A S; Hannun, R A; Lapson, L B; Hanisco, T F; Anderson, J G

    2014-04-01

    High abundances of iodine monoxide (IO) are known to exist and to participate in local photochemistry of the marine boundary layer. Of particular interest are the roles IO plays in the formation of new particles in coastal marine environments and in depletion episodes of ozone and mercury in the Arctic polar spring. This paper describes a ground-based instrument that measures IO at mixing ratios less than one part in 10(12). The IO radical is measured by detecting laser-induced fluorescence at wavelengths longer that 500 nm. Tunable visible light is used to pump the A(2)Π3/2 (v(') = 2) ← X(2)Π3/2 (v(″) = 0) transition of IO near 445 nm. The laser light is produced by a solid-state, Nd:YAG-pumped Ti:Sapphire laser at 5 kHz repetition rate. The laser-induced fluorescence instrument performs reliably with very high signal-to-noise ratios (>10) achieved in short integration times (<1 min). The observations from a validation deployment to the Shoals Marine Lab on Appledore Island, ME are presented and are broadly consistent with in situ observations from European Coastal Sites. Mixing ratios ranged from the instrumental detection limit (<1 pptv) to 10 pptv. These data represent the first in situ point measurements of IO in North America.

  14. Assessment of the iodine concentration in table salt at the production stage in South Africa.

    PubMed Central

    Jooste, Pieter L.

    2003-01-01

    OBJECTIVE: To determine the iodine content of iodized salt at the production stage, to assess the perceptions and knowledge of salt producers about the prevention and control of iodine deficiency, and to examine the internal quality control procedures used during iodization in South Africa. METHOD: Salt samples were collected for iodine analysis by titration from the 12 producers iodizing salt in South Africa. Information on the producers' knowledge of iodine deficiency disorders and on internal quality control was obtained by means of questionnaires. FINDINGS: The legal requirement of 40-60 ppm iodine was met in 30.9% of salt samples; 57.9% contained more than 30 ppm iodine; 34.8% contained under 20 ppm iodine. There were shortcomings in perceptions and knowledge about iodine deficiency disorders and in the internal quality control procedures of a substantial proportion of the producers. CONCLUSION: In order to encourage and support salt producers to achieve optimal iodization there should be an information, education and communication strategy aimed at improving knowledge of iodine deficiency disorders and at raising the standard of internal quality control procedures. External monitoring should continue. PMID:12973644

  15. Need for coordinated programs to improve global health by optimizing salt and iodine intake.

    PubMed

    Campbell, Norm R C; Dary, Omar; Cappuccio, Francesco P; Neufeld, Lynnette M; Harding, Kim B; Zimmermann, Michael B

    2012-10-01

    High dietary salt is a major cause of increased blood pressure, the leading risk for death worldwide. The World Health Organization (WHO) has recommended that salt intake be less than 5 g/day, a goal that only a small proportion of people achieve. Iodine deficiency can cause cognitive and motor impairment and, if severe, hypothyroidism with serious mental and growth retardation. More than 2 billion people worldwide are at risk of iodine deficiency. Preventing iodine deficiency by using salt fortified with iodine is a major global public health success. Programs to reduce dietary salt are technically compatible with programs to prevent iodine deficiency through salt fortification. However, for populations to fully benefit from optimum intake of salt and iodine, the programs must be integrated. This review summarizes the scientific basis for salt reduction and iodine fortification programs, the compatibility of the programs, and the steps that need to be taken by the WHO, national governments, and nongovernmental organizations to ensure that populations fully benefit from optimal intake of salt and iodine. Specifically, expert groups must be convened to help countries implement integrated programs and context-specific case studies of successfully integrated programs; lessons learned need to be compiled and disseminated. Integrated surveillance programs will be more efficient and will enhance current efforts to optimize intake of iodine and salt. For populations to fully benefit, governments need to place a high priority on integrating these two important public health programs. PMID:23299289

  16. Prevalence of goitre and urinary iodine status of primary-school children in Lesotho.

    PubMed Central

    Sebotsa, Masekonyela Linono Damane; Dannhauser, Andre; Jooste, Pieter L.; Joubert, Gina

    2003-01-01

    OBJECTIVE: To estimate the prevalence of goitre, urinary iodine status, coverage of supplementation of iodized oil capsules, and current use of iodized salt in children in Lesotho. METHODS: Cross-sectional study of children from 50 primary schools in Lesotho. Thyroid glands of children aged 8-12 years were measured by palpation and graded according to the WHO, UNICEF, and the International Council for the Control of Iodine Deficiency's (ICCIDD) joint criteria. The use of iodized oil capsules was determined by a structured questionnaire and verified with the children's health booklets. Iodine content of household salt samples was analysed. Casual urine samples were analysed for urinary iodine. FINDINGS: Median urinary iodine concentrations of 26.3 microg/l (range 22.3-47.9 microg/l) indicated moderate iodine deficiency. More children in the mountains than in the lowlands were severely iodine deficient (17.7% vs 1.9%). Adjusted prevalence of goitre (4.9%) increased with age, was higher in girls than boys, and ranged from 2.2% to 8.8% in the different districts; this indicated no public health problem. Overall, 94.4% of salt samples were iodized, and coverage of supplementation with iodized oil capsules was 55.1%. CONCLUSION: Mild-to-moderate iodine deficiency exists in Lesotho. Iodine deficiency was more severe in the mountains than the lowlands and is still a concern for public health. Use of iodized salt coupled with iodized oil supplementation effectively controls iodine deficiency disorders. Effective monitoring programmes would ensure the use of adequately iodized salt throughout Lesotho and serve to evaluate progress towards optimal iodine nutrition. Iodized oil capsule supplementation should continue in the mountains. PMID:12640473

  17. Iodine intake in human nutrition: a systematic literature review

    PubMed Central

    Gunnarsdottir, Ingibjörg; Dahl, Lisbeth

    2012-01-01

    The present literature review is a part of the NNR5 project with the aim of reviewing and updating the scientific basis of the 4th edition of the Nordic Nutrition Recommendations (NNR) issued in 2004. The main objective of the review is to assess the influence of different intakes of iodine at different life stages (infants, children, adolescents, adults, elderly, and during pregnancy and lactation) in order to estimate the requirement for adequate growth, development, and maintenance of health. The literature search resulted in 1,504 abstracts. Out of those, 168 papers were identified as potentially relevant. Full paper selection resulted in 40 papers that were quality assessed (A, B, or C). The grade of evidence was classified as convincing, probable, suggestive, and no conclusion. We found suggestive evidence for improved maternal iodine status and thyroid function by iodine supplementation during pregnancy. Suggestive evidence was found for the relationship between improved thyroid function (used as an indicator of iodine status) during pregnancy and cognitive function in the offspring up to 18 months of age. Moderately to severely iodine-deficient children will probably benefit from iodine supplementation or improved iodine status in order to improve their cognitive function, while only one study showed improved cognitive function following iodine supplementation in children from a mildly iodine-deficient area (no conclusion). No conclusions can be drawn related to other outcomes included in our review. There are no new data supporting changes in dietary reference values for children or adults. The rationale for increasing the dietary reference values for pregnant and lactating women in the NNR5 needs to be discussed in a broader perspective, taking iodine status of pregnant women in the Nordic countries into account. PMID:23060737

  18. Kindling-induced learning deficiency and possible cellular and molecular involved mechanisms.

    PubMed

    Sherafat, Mohammad Amin; Ronaghi, Abdolaziz; Ahmad-Molaei, Leila; Nejadhoseynian, Mohammad; Ghasemi, Rasoul; Hosseini, Arman; Naderi, Nima; Motamedi, Fereshteh

    2013-06-01

    Hippocampus learning disturbance is a major symptom of patients with seizure, hence hippocampal dysfunction has essential role in worsening the disease. Hippocampal formation includes neurons and myelinated fibers that are necessary for acquisition and consolidation of memory, long-term potentiation and learning activity. The exact mechanism by which seizure can decrease memory and learning activity of hippocampus remains unknown. In the present study, electrical kindling-induced learning deficit in rats was evaluated by Morris water maze (MWM) test. The hippocampus was removed and changes in neurons and myelin sheaths around hippocampal fibers were investigated using histological and immunohistochemical methods. Demyelination was assessed by luxol fast blue staining, and immunohistological staining of myelin-binding protein (MBP). The TUNEL assay was used for evaluation of neuronal apoptosis and the glial fibriliary acetic protein (GFAP) was used for assessment of inflammatory reaction. The results indicated that electrical kindling of hippocampus could induce deficiency in spatial learning and memory as compared to control group. In addition, electrical kindling caused damage to the myelin sheath around hippocampal fibers and produced vast demyelination. Furthermore, an increase in the number of apoptotic cells in hippocampal slices was observed. In addition, inflammatory response was higher in kindled animals as compared to the control group. The results suggested that the decrease in learning and memory in kindled animals is likely due to demyelination and augmentation in apoptosis rate accompanied by inflammatory reaction in hippocampal neurons of kindled rats.

  19. UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.

    PubMed Central

    Bregman, D B; Halaban, R; van Gool, A J; Henning, K A; Friedberg, E C; Warren, S L

    1996-01-01

    Damage to actively transcribed DNA is preferentially repaired by the transcription-coupled repair (TCR) system. TCR requires RNA polymerase II (Pol II), but the mechanism by which repair enzymes preferentially recognize and repair DNA lesions on Pol II-transcribed genes is incompletely understood. Herein we demonstrate that a fraction of the large subunit of Pol II (Pol II LS) is ubiquitinated after exposing cells to UV-radiation or cisplatin but not several other DNA damaging agents. This novel covalent modification of Pol II LS occurs within 15 min of exposing cells to UV-radiation and persists for about 8-12 hr. Ubiquitinated Pol II LS is also phosphorylated on the C-terminal domain. UV-induced ubiquitination of Pol II LS is deficient in fibroblasts from individuals with two forms of Cockayne syndrome (CS-A and CS-B), a rare disorder in which TCR is disrupted. UV-induced ubiquitination of Pol II LS can be restored by introducing cDNA constructs encoding the CSA or CSB genes, respectively, into CS-A or CS-B fibroblasts. These results suggest that ubiquitination of Pol II LS plays a role in the recognition and/or repair of damage to actively transcribed genes. Alternatively, these findings may reflect a role played by the CSA and CSB gene products in transcription. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8876179

  20. UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.

    PubMed

    Bregman, D B; Halaban, R; van Gool, A J; Henning, K A; Friedberg, E C; Warren, S L

    1996-10-15

    Damage to actively transcribed DNA is preferentially repaired by the transcription-coupled repair (TCR) system. TCR requires RNA polymerase II (Pol II), but the mechanism by which repair enzymes preferentially recognize and repair DNA lesions on Pol II-transcribed genes is incompletely understood. Herein we demonstrate that a fraction of the large subunit of Pol II (Pol II LS) is ubiquitinated after exposing cells to UV-radiation or cisplatin but not several other DNA damaging agents. This novel covalent modification of Pol II LS occurs within 15 min of exposing cells to UV-radiation and persists for about 8-12 hr. Ubiquitinated Pol II LS is also phosphorylated on the C-terminal domain. UV-induced ubiquitination of Pol II LS is deficient in fibroblasts from individuals with two forms of Cockayne syndrome (CS-A and CS-B), a rare disorder in which TCR is disrupted. UV-induced ubiquitination of Pol II LS can be restored by introducing cDNA constructs encoding the CSA or CSB genes, respectively, into CS-A or CS-B fibroblasts. These results suggest that ubiquitination of Pol II LS plays a role in the recognition and/or repair of damage to actively transcribed genes. Alternatively, these findings may reflect a role played by the CSA and CSB gene products in transcription. PMID:8876179

  1. Altered Energy Homeostasis and Resistance to Diet-Induced Obesity in KRAP-Deficient Mice

    PubMed Central

    Fujimoto, Takahiro; Miyasaka, Kyoko; Koyanagi, Midori; Tsunoda, Toshiyuki; Baba, Iwai; Doi, Keiko; Ohta, Minoru; Kato, Norihiro; Sasazuki, Takehiko; Shirasawa, Senji

    2009-01-01

    Obesity and related metabolic disorders have become leading causes of adult morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule, however, its physiological roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP−/−) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP−/− mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia. Notably, glucose uptake in the brown adipose tissue (BAT) in KRAP−/− mice is enhanced in an insulin-independent manner, suggesting that BAT is involved in altered energy homeostasis in KRAP−/− mice, although UCP (Uncoupling protein) expressions are not altered. Of interest is the down-regulation of fatty acid metabolism-related molecules, including acetyl-CoA carboxylase (ACC)-1, ACC-2 and fatty acid synthase in the liver of KRAP−/− mice, which could in part account for the metabolic phenotype in KRAP−/− mice. Thus, KRAP is a novel regulator in whole-body energy homeostasis and may be a therapeutic target in obesity and related diseases. PMID:19156225

  2. Plasmepsin 4-Deficient Plasmodium berghei Are Virulence Attenuated and Induce Protective Immunity against Experimental Malaria

    PubMed Central

    Spaccapelo, Roberta; Janse, Chris J.; Caterbi, Sara; Franke-Fayard, Blandine; Bonilla, J. Alfredo; Syphard, Luke M.; Di Cristina, Manlio; Dottorini, Tania; Savarino, Andrea; Cassone, Antonio; Bistoni, Francesco; Waters, Andrew P.; Dame, John B.; Crisanti, Andrea

    2010-01-01

    Plasmodium parasites lacking plasmepsin 4 (PM4), an aspartic protease that functions in the lysosomal compartment and contributes to hemoglobin digestion, have only a modest decrease in the asexual blood-stage growth rate; however, PM4 deficiency in the rodent malaria parasite Plasmodium berghei results in significantly less virulence than that for the parental parasite. P. berghei Δpm4 parasites failed to induce experimental cerebral malaria (ECM) in ECM-susceptible mice, and ECM-resistant mice were able to clear infections. Furthermore, after a single infection, all convalescent mice were protected against subsequent parasite challenge for at least 1 year. Real-time in vivo parasite imaging and splenectomy experiments demonstrated that protective immunity acted through antibody-mediated parasite clearance in the spleen. This work demonstrates, for the first time, that a single Plasmodium gene disruption can generate virulence-attenuated parasites that do not induce cerebral complications and, moreover, are able to stimulate strong protective immunity against subsequent challenge with wild-type parasites. Parasite blood-stage attenuation should help identify protective immune responses against malaria, unravel parasite-derived factors involved in malarial pathologies, such as cerebral malaria, and potentially pave the way for blood-stage whole organism vaccines. PMID:20019192

  3. Antiosteoclastic activity of milk thistle extract after ovariectomy to suppress estrogen deficiency-induced osteoporosis.

    PubMed

    Kim, Jung-Lye; Kim, Yun-Ho; Kang, Min-Kyung; Gong, Ju-Hyun; Han, Seoung-Jun; Kang, Young-Hee

    2013-01-01

    Bone integrity abnormality and imbalance between bone formation by osteoblasts and bone resorption by osteoclasts are known to result in metabolic bone diseases such as osteoporosis. Silymarin-rich milk thistle extract (MTE) and its component silibinin enhanced alkaline phosphatase activity of osteoblasts but reduced tartrate-resistant acid phosphatase (TRAP) activity of osteoclasts. The osteoprotective effects of MTE were comparable to those of estrogenic isoflavone. Low-dose combination of MTE and isoflavone had a pharmacological synergy that may be useful for osteogenic activity. This study attempted to reveal the suppressive effects of MTE on bone loss. C57BL/6 female mice were ovariectomized (OVX) as a model for postmenopausal osteopenia and orally administered 10 mg/kg MTE or silibinin for 8 weeks. The sham-operated mice served as estrogen controls. The treatment of ovariectomized mice with nontoxic MTE and silibinin improved femoral bone mineral density and serum receptor activator of nuclear factor- κB ligand/osteoprotegerin ratio, an index of osteoclastogenic stimulus. In addition, the administration of MTE or silibinin inhibited femoral bone loss induced by ovariectomy and suppressed femoral TRAP activity and cathepsin K induction responsible for osteoclastogenesis and bone resorption. Collectively, oral dosage of MTE containing silibinin in the preclinical setting is effective in preventing estrogen deficiency-induced bone loss.

  4. Recreational nitrous oxide abuse-induced vitamin B12 deficiency in a patient presenting with hyperpigmentation of the skin.

    PubMed

    Chiang, Tsung-Ta; Hung, Chih-Tsung; Wang, Wei-Ming; Lee, Jiunn-Tay; Yang, Fu-Chi

    2013-05-01

    Vitamin B12 deficiency causes skin hyperpigmentation, subacute combined degeneration of the spinal cord, and megaloblastic anemia. Although vitamin B12 deficiency rarely occurs in well-nourished, healthy, young people, nitrous oxide (N2O) intoxication is an important cause of vitamin B12 deficiency in this cohort. N2O, a colorless gas used as an anesthetic since the late 19th century because of its euphoric and analgesic qualities, is now used as a recreational drug and is available via the Internet and at clubs. Here, we describe the case of a 29-year-old woman presenting with skin hyperpigmentation as her only initial symptom after N2O abuse for approximately 2 years. N2O intoxication-induced vitamin B12 deficiency was diagnosed based on the skin pigmentation that had manifested over the dorsa of her fingers, toes, and trunk, coupled with myeloneuropathy of the posterior and lateral columns, a low serum vitamin B12 level, an elevated serum homocysteine level, and the N2O exposure revealed while establishing the patient's history. Symptoms improved significantly with vitamin B12 treatment. We recommend that dermatologists consider N2O intoxication-induced vitamin B12 deficiency as a potential cause of skin hyperpigmentation and myeloneuropathy of the posterior and lateral columns in young, otherwise healthy patients. Failure to recognize this presentation may result in inappropriate treatment, thus affecting patients' clinical outcomes. PMID:23898268

  5. Influence of Corticosteroids and Vitamin E Deficiency on Onset and Cytopathology of Radiation-Induced Cataract

    NASA Astrophysics Data System (ADS)

    Junk, A. K.; Worgul, B. V.

    Cataracts characteristic of those arising from radiation exposure have been reported among the astronaut and cosmonaut corps. This being the case it is critical to appreciate how radiogenic cataracts relate to those arising from other exogenous causes such as therapeutics, which may, one day, have to be administered on an extended mission. Because they produce precisely the same clinical picture, corticosteroids are examples of a class of drugs that potentially can exacerbate damage to the lens from radiation. On the other hand, Vitamin E, a free radical scavenger, has been shown to ameliorate oxidative damage as caused by ionizing radiation and evidence is accumulating that it may constitute protection from radiogenic damage. An experimental study was conducted to understand if corticosteroids with and in the absence of Vitamin E deficiency modulate the onset of cataract induced by ionizing radiation. The right eyes of 72 28-day-old Brown-Norway rats were irradiated with 6 Gy of 240 kV X-rays, the shielded left eyes served as controls. Half of the animals were maintained on a Vitamin E free diet after irradiation, the others were kept on regular chow. In each nutritional group 18 rats additionally received dexamethasone. The initial daily dose of 10 mg/kg body weight injected subcutaneously was reduced to 0.5 mg/kg over the course of 6 months. Cataract onset and development were followed by weekly slit-lamp exam. After 6 month the lenses were harvested for microscopic analyses. Irradiated eyes in all treatment subgroups showed early cataract onset [5 wks versus 11 wks in controls (p<0.0001)]. Corticosteroids accounted for accelerated cataract development in both irradiated (p<0.0005) and non-irradiated eyes (p<0.0001) relative to respective control eyes. Vitamin E deficiency did not affect cataract incidence in combination with radiation or steroids alone. Unexpectedly, when compared to irradiated controls, cataract development was inhibited in the group that

  6. Influence of corticosteroids and vitamin E deficiency on onset of radiation-induced cataract

    NASA Astrophysics Data System (ADS)

    Junk, A. K.; Worgul, B. W.

    Cataracts characteristic of those arising from radiation exposure have been reported among the astronaut and cosmonaut corps. This being the case it is critical to appreciate how radiogenic cataracts relate to those arising from other exogenous causes such as therapeutics, which may, one day, have to be administered on an extended mission. Because they produce precisely the same clinical picture, corticosteroids are examples of a class of drugs that potentially can exacerbate damage to the lens from radiation. On the other hand, Vitamin E, a free radical scavenger, has been shown to ameliorate oxidative damage as caused by ionizing radiation and evidence is accumulating that it may constitute protection from radiogenic damage. An experimental study was conducted to understand if corticosteroids with, and in the absence of Vitamin E deficiency modulate the onset of cataract induced by ionizing radiation. The right eyes of seventy-two 28-day-old Brown-Norway rats were irradiated with 6 Gy of 240 kV X-rays, the shielded left eyes served as controls. Half of the animals were maintained on a Vitamin E free diet after irradiation, the others were kept on standard chow. Fifty per cent of the animals in each nutritional group received dexamethasone. The initial daily dose of 10 mg/kg body weight injected subcutaneously was reduced to 0.5 mg/kg over the course of six months. Cataract onset and development were followed by weekly slit-lamp exam. After six month the lenses were harvested for microscopic analyses. Irradiated eyes in all treatment subgroups showed early cataract onset [5 wks vs. 11 wks in controls ( p < 0.0001)]. Corticosteroids accounted for accelerated cataract development in both irradiated ( p < 0.0005) and non-irradiated eyes ( p < 0.0001) relative to respective control eyes. Vitamin E deficiency did not affect cataract incidence in combination with radiation or steroids alone. Unexpectedly, when compared to irradiated controls, cataract development was

  7. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice.

    PubMed

    Kumar, Sudhir; Wang, Jiang; Rani, Richa; Gandhi, Chandrashekhar R

    2016-01-01

    Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8-10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID:26808690

  8. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice

    PubMed Central

    Kumar, Sudhir; Wang, Jiang; Rani, Richa; Gandhi, Chandrashekhar R.

    2016-01-01

    Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8–10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID:26808690

  9. Strigolactones are required for nitric oxide to induce root elongation in response to nitrogen and phosphate deficiencies in rice.

    PubMed

    Sun, Huwei; Bi, Yang; Tao, Jinyuan; Huang, Shuangjie; Hou, Mengmeng; Xue, Ren; Liang, Zhihao; Gu, Pengyuan; Yoneyama, Koichi; Xie, Xiaonan; Shen, Qirong; Xu, Guohua; Zhang, Yali

    2016-07-01

    The response of the root system architecture to nutrient deficiencies is critical for sustainable agriculture. Nitric oxide (NO) is considered a key regulator of root growth, although the mechanisms remain unknown. Phenotypic, cellular and genetic analyses were undertaken in rice to explore the role of NO in regulating root growth and strigolactone (SL) signalling under nitrogen-deficient and phosphate-deficient conditions (LN and LP). LN-induced and LP-induced seminal root elongation paralleled NO production in root tips. NO played an important role in a shared pathway of LN-induced and LP-induced root elongation via increased meristem activity. Interestingly, no responses of root elongation were observed in SL d mutants compared with wild-type plants, although similar NO accumulation was induced by sodium nitroprusside (SNP) application. Application of abamine (the SL inhibitor) reduced seminal root length and pCYCB1;1::GUS expression induced by SNP application in wild type; furthermore, comparison with wild type showed lower SL-signalling genes in nia2 mutants under control and LN treatments and similar under SNP application. Western blot analysis revealed that NO, similar to SL, triggered proteasome-mediated degradation of D53 protein levels. Therefore, we presented a novel signalling pathway in which NO-activated seminal root elongation under LN and LP conditions, with the involvement of SLs. PMID:27194103

  10. Strigolactones are required for nitric oxide to induce root elongation in response to nitrogen and phosphate deficiencies in rice.

    PubMed

    Sun, Huwei; Bi, Yang; Tao, Jinyuan; Huang, Shuangjie; Hou, Mengmeng; Xue, Ren; Liang, Zhihao; Gu, Pengyuan; Yoneyama, Koichi; Xie, Xiaonan; Shen, Qirong; Xu, Guohua; Zhang, Yali

    2016-07-01

    The response of the root system architecture to nutrient deficiencies is critical for sustainable agriculture. Nitric oxide (NO) is considered a key regulator of root growth, although the mechanisms remain unknown. Phenotypic, cellular and genetic analyses were undertaken in rice to explore the role of NO in regulating root growth and strigolactone (SL) signalling under nitrogen-deficient and phosphate-deficient conditions (LN and LP). LN-induced and LP-induced seminal root elongation paralleled NO production in root tips. NO played an important role in a shared pathway of LN-induced and LP-induced root elongation via increased meristem activity. Interestingly, no responses of root elongation were observed in SL d mutants compared with wild-type plants, although similar NO accumulation was induced by sodium nitroprusside (SNP) application. Application of abamine (the SL inhibitor) reduced seminal root length and pCYCB1;1::GUS expression induced by SNP application in wild type; furthermore, comparison with wild type showed lower SL-signalling genes in nia2 mutants under control and LN treatments and similar under SNP application. Western blot analysis revealed that NO, similar to SL, triggered proteasome-mediated degradation of D53 protein levels. Therefore, we presented a novel signalling pathway in which NO-activated seminal root elongation under LN and LP conditions, with the involvement of SLs.

  11. The Vacuolar Manganese Transporter MTP8 Determines Tolerance to Iron Deficiency-Induced Chlorosis in Arabidopsis1[OPEN

    PubMed Central

    2016-01-01

    Iron (Fe) deficiency is a widespread nutritional disorder on calcareous soils. To identify genes involved in the Fe deficiency response, Arabidopsis (Arabidopsis thaliana) transfer DNA insertion lines were screened on a high-pH medium with low Fe availability. This approach identified METAL TOLERANCE PROTEIN8 (MTP8), a member of the Cation Diffusion Facilitator family, as a critical determinant for the tolerance to Fe deficiency-induced chlorosis, also on soil substrate. Subcellular localization to the tonoplast, complementation of a manganese (Mn)-sensitive Saccharomyces cerevisiae yeast strain, and Mn sensitivity of mtp8 knockout mutants characterized the protein as a vacuolar Mn transporter suitable to prevent plant cells from Mn toxicity. MTP8 expression was strongly induced on low-Fe as well as high-Mn medium, which were both strictly dependent on the transcription factor FIT, indicating that high-Mn stress induces Fe deficiency. mtp8 mutants were only hypersensitive to Fe deficiency when Mn was present in the medium, which further suggested an Mn-specific role of MTP8 during Fe limitation. Under those conditions, mtp8 mutants not only translocated more Mn to the shoot than did wild-type plants but suffered in particular from critically low Fe concentrations and, hence, Fe chlorosis, although the transcriptional Fe deficiency response was up-regulated more strongly in mtp8. The diminished uptake of Fe from Mn-containing low-Fe medium by mtp8 mutants was caused by an impaired ability to boost the ferric chelate reductase activity, which is an essential process in Fe acquisition. These findings provide a mechanistic explanation for the long-known interference of Mn in Fe nutrition and define the molecular processes by which plants alleviate this antagonism. PMID:26668333

  12. Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish--implication in neural tube defects and Alzheimer's diseases.

    PubMed

    Kao, Tseng-Ting; Chu, Chia-Yi; Lee, Gang-Hui; Hsiao, Tsun-Hsien; Cheng, Nai-Wei; Chang, Nan-Shan; Chen, Bing-Hung; Fu, Tzu-Fun

    2014-11-01

    Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-γ-glutamyl hydrolase (γGH). Impeded neural crest cell migration was observed in the transgenic embryos when folate deficiency was induced in early stages, leading to defective neural tube closure and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the phenotypic anomalies, supporting the causal link between the increased oxidative stress and the folate deficiency-induced abnormalities. When folate deficiency was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau protein were found in the fish brain cryo-sections. Increased autophagy and accumulation of acidic autolysosome were apparent in folate deficient neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine supplementation. Decreased expression of cathepsin B, a lysosomal protease, was also observed in cells and tissue with folate deficiency. We concluded that folate deficiency-induced oxidative stress contributed to the folate deficiency-associated neuropathogenesis in both early and late stages of life.

  13. Iodine environmental availability and human intake in oceanic islands: Azores as a case-study.

    PubMed

    Linhares, Diana Paula Silva; Garcia, Patrícia Ventura; Almada, Alexandra; Ferreira, Teresa; Queiroz, Gabriela; Cruz, José Virgílio; Rodrigues, Armindo dos Santos

    2015-12-15

    Iodine deficiency is the most common cause of preventable mental impairment. Although several studies have established an association between ocean proximity and iodine environmental availability, recent studies revealed an inadequate iodine intake in the Azorean islands. In this study, we aim to understand the underlying causes of iodine environmental availability in oceanic islands and its association with iodine intake in schoolchildren, using the Azores as case-study. Iodine concentration in soil and grass pasture was measured by INAA and in drinking water by spectrophotometry. Urinary iodine concentration (UIC) in schoolchildren was assessed by ICP-MS in a randomized cross-sectional survey with 315 participants from S. Miguel (study group) and Sta. Maria islands (reference group). A validated diet questionnaire assessing sources of iodine was recorded. The iodine concentration in soils of the reference group was significantly higher than in the study group (58.1ppm vs. 14.5ppm, respectively; p=0.001). The prevalence of schoolchildren with inadequate UIC was significantly higher in the study group than in the reference one (63.0% vs. 37.8%, respectively; p<0.001). Chronic exposure to low iodine environmental availability was significantly associated with the exacerbation in iodine deficiency, with a risk 4.94 times higher in the study group. The differences observed in the studied islands are related with each island geomorphology (soil properties and orography) and climate, which can promote or inhibit iodine environmental availability, contributing distinctively to iodine bioavailability and human intake. These findings draw attention to an urgent need for a full investigation of Azores iodine status to apply evidence-based recommendations for iodine supplementation.

  14. Iodine environmental availability and human intake in oceanic islands: Azores as a case-study.

    PubMed

    Linhares, Diana Paula Silva; Garcia, Patrícia Ventura; Almada, Alexandra; Ferreira, Teresa; Queiroz, Gabriela; Cruz, José Virgílio; Rodrigues, Armindo dos Santos

    2015-12-15

    Iodine deficiency is the most common cause of preventable mental impairment. Although several studies have established an association between ocean proximity and iodine environmental availability, recent studies revealed an inadequate iodine intake in the Azorean islands. In this study, we aim to understand the underlying causes of iodine environmental availability in oceanic islands and its association with iodine intake in schoolchildren, using the Azores as case-study. Iodine concentration in soil and grass pasture was measured by INAA and in drinking water by spectrophotometry. Urinary iodine concentration (UIC) in schoolchildren was assessed by ICP-MS in a randomized cross-sectional survey with 315 participants from S. Miguel (study group) and Sta. Maria islands (reference group). A validated diet questionnaire assessing sources of iodine was recorded. The iodine concentration in soils of the reference group was significantly higher than in the study group (58.1ppm vs. 14.5ppm, respectively; p=0.001). The prevalence of schoolchildren with inadequate UIC was significantly higher in the study group than in the reference one (63.0% vs. 37.8%, respectively; p<0.001). Chronic exposure to low iodine environmental availability was significantly associated with the exacerbation in iodine deficiency, with a risk 4.94 times higher in the study group. The differences observed in the studied islands are related with each island geomorphology (soil properties and orography) and climate, which can promote or inhibit iodine environmental availability, contributing distinctively to iodine bioavailability and human intake. These findings draw attention to an urgent need for a full investigation of Azores iodine status to apply evidence-based recommendations for iodine supplementation. PMID:26318689

  15. Abrogation of hybrid resistance to bone marrow engraftment by graft versus host induced immune deficiency

    SciTech Connect

    Hakim, F.T.; Shearer, G.M.

    1986-03-01

    Lethally irradiated F/sub 1/ mice, heterozygous at the hematopoietic histocompatibility (Hh) locus at H-2D/sup b/, reject bone marrow grafts from homozygous H-2/sup b/ parents. This hybrid resistance (HR) is reduced by prior injection of H-2/sup b/ parental spleen cells. Since injection of parental spleen cells produces a profound suppression of F/sub 1/ immune functions, the authors investigated whether parental-induced abrogation of HR was due to graft-vs-host induced immune deficiency (GVHID). HR was assessed by quantifying engraftment in irradiated mice using /sup 125/I-IUdR spleen uptake; GVHID by measuring generation of cytotoxic T lymphocytes (CTL) from unirradiated mice. They observed correlation in time course, spleen dose dependence and T cell dependence between GVHID and loss of HR. The injection of B10 recombinant congenic spleens into (B10 x B10.A) F/sub 1/ mice, prior to grafting with B10 marrow, demonstrated that only those disparities in major histocompatibility antigens which generated GVHID would result in loss of HR. Spleens from (B10 x B10.A(2R))F/sub 1/ mice (Class I disparity only) did not induce GVHID or affect HR, while (B10 x B10.A(5R)F/sub 1/ spleens (Class I and II disparity) abrogated CTL generation and HR completely. GVHID produced by a Class II only disparity, as in (B10 x B10.A(5R))F/sub 1/ spleens injected into (B6/sup bm12 x B10.A(5R))F/sub 1/ mice, was also sufficient to markedly reduce HR to B10 bone marrow. Modulation of hematopoietic graft rejection by GVHID may affect marrow engraftment in man.

  16. Median Urinary Iodine Concentrations Are Indicative of Adequate Iodine Status among Women of Reproductive Age in Prey Veng, Cambodia.

    PubMed

    Karakochuk, Crystal D; Michaux, Kristina D; Chai, Tze L; Chan, Benny B; Whitfield, Kyly C; Barr, Susan I; McLean, Judy; Talukder, Aminuzzaman; Hou, Kroeun; Ly, Sokhoing; Green, Tim J

    2016-03-01

    Iodine deficiency disorders are estimated to affect over 1.9 million people worldwide. Iodine deficiency is especially serious for women during pregnancy and lactation because of the negative consequences for both mother and infant. The aim of this cross-sectional study was to determine the median urinary iodine concentration (UIC) as a population-level indicator of iodine status among rural women farmers of reproductive age (18-45 years) in the province of Prey Veng, Cambodia. A total of 450 women provided a spot morning urine sample in 2012. Of those women, 93% (n = 420) were non-pregnant and 7% (n = 30) were pregnant at the time of collection. UIC was quantified using the Sandell-Kolthoff reaction with modifications. The median UIC of non-pregnant (139 μg/L) and pregnant women (157 μg/L) were indicative of adequate iodine status using the WHO/UNICEF/ICCIDD epidemiological criteria for both groups (median UIC between 100-199 and 150-249 μg/L, respectively). We conclude that non-pregnant and pregnant women in rural Prey Veng, Cambodia had adequate iodine status based on single spot morning urine samples collected in 2012. More research is warranted to investigate iodine status among larger and more representative populations of women in Cambodia, especially in light of recent policy changes to the national program for universal salt iodization. PMID:26950151

  17. Median Urinary Iodine Concentrations Are Indicative of Adequate Iodine Status among Women of Reproductive Age in Prey Veng, Cambodia

    PubMed Central

    Karakochuk, Crystal D.; Michaux, Kristina D.; Chai, Tze L.; Chan, Benny B.; Whitfield, Kyly C.; Barr, Susan I.; McLean, Judy; Talukder, Aminuzzaman; Hou, Kroeun; Ly, Sokhoing; Green, Tim J.

    2016-01-01

    Iodine deficiency disorders are estimated to affect over 1.9 million people worldwide. Iodine deficiency is especially serious for women during pregnancy and lactation because of the negative consequences for both mother and infant. The aim of this cross-sectional study was to determine the median urinary iodine concentration (UIC) as a population-level indicator of iodine status among rural women farmers of reproductive age (18–45 years) in the province of Prey Veng, Cambodia. A total of 450 women provided a spot morning urine sample in 2012. Of those women, 93% (n = 420) were non-pregnant and 7% (n = 30) were pregnant at the time of collection. UIC was quantified using the Sandell-Kolthoff reaction with modifications. The median UIC of non-pregnant (139 μg/L) and pregnant women (157 μg/L) were indicative of adequate iodine status using the WHO/UNICEF/ICCIDD epidemiological criteria for both groups (median UIC between 100–199 and 150–249 μg/L, respectively). We conclude that non-pregnant and pregnant women in rural Prey Veng, Cambodia had adequate iodine status based on single spot morning urine samples collected in 2012. More research is warranted to investigate iodine status among larger and more representative populations of women in Cambodia, especially in light of recent policy changes to the national program for universal salt iodization. PMID:26950151

  18. Median Urinary Iodine Concentrations Are Indicative of Adequate Iodine Status among Women of Reproductive Age in Prey Veng, Cambodia.

    PubMed

    Karakochuk, Crystal D; Michaux, Kristina D; Chai, Tze L; Chan, Benny B; Whitfield, Kyly C; Barr, Susan I; McLean, Judy; Talukder, Aminuzzaman; Hou, Kroeun; Ly, Sokhoing; Green, Tim J

    2016-03-03

    Iodine deficiency disorders are estimated to affect over 1.9 million people worldwide. Iodine deficiency is especially serious for women during pregnancy and lactation because of the negative consequences for both mother and infant. The aim of this cross-sectional study was to determine the median urinary iodine concentration (UIC) as a population-level indicator of iodine status among rural women farmers of reproductive age (18-45 years) in the province of Prey Veng, Cambodia. A total of 450 women provided a spot morning urine sample in 2012. Of those women, 93% (n = 420) were non-pregnant and 7% (n = 30) were pregnant at the time of collection. UIC was quantified using the Sandell-Kolthoff reaction with modifications. The median UIC of non-pregnant (139 μg/L) and pregnant women (157 μg/L) were indicative of adequate iodine status using the WHO/UNICEF/ICCIDD epidemiological criteria for both groups (median UIC between 100-199 and 150-249 μg/L, respectively). We conclude that non-pregnant and pregnant women in rural Prey Veng, Cambodia had adequate iodine status based on single spot morning urine samples collected in 2012. More research is warranted to investigate iodine status among larger and more representative populations of women in Cambodia, especially in light of recent policy changes to the national program for universal salt iodization.

  19. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    SciTech Connect

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. )

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  20. Reconstruction of limbal stem cell deficient corneal surface with induced human bone marrow mesenchymal stem cells on amniotic membrane.

    PubMed

    Rohaina, Che Man; Then, Kong Yong; Ng, Angela Min Hwei; Wan Abdul Halim, Wan Haslina; Zahidin, Aida Zairani Mohd; Saim, Aminuddin; Idrus, Ruszymah B H

    2014-03-01

    The cornea can be damaged by a variety of clinical disorders or chemical, mechanical, and thermal injuries. The objectives of this study were to induce bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface defects in a limbal stem cell deficiency model. BMSCs were induced to corneal lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation of corneal stem cell markers; β1-integrin, C/EBPδ, ABCG2, and p63, increased protein expression of CK3 and p63 significantly compared with the uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on amniotic membrane in a transwell co-culture system and were grown in limbal medium. Limbal stem cell deficiency models were induced by alkaline injury, and the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed remarkable improvement in corneal regeneration in terms of corneal clarity and reduced vascularization. Histologic and optical coherence tomography analyses demonstrated comparable corneal thickness and achieved stratified epithelium with a compact stromal layer resembling that of normal cornea. CK3 and p63 were expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced into corneal epithelial lineage, and these cells are viable for the formation of TEC, to be used for the reconstruction of the corneal surface in the limbal stem cell deficient model.

  1. Medical effects of iodine disinfection products in spacecraft water

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L.; Janik, Daniel S.; Thorstenson, Yvonne R.

    1987-01-01

    Various iodination products (IDPs), including iodinated and iodine-induced new compounds, will be present in the iodine-disinfected water that is expected to be used by crews on the NASA Space Station and on long duration missions. The metabolic intermediaries created by such a process may be more important to crew health than the parent IDPs, and reclamation and recycling may be expected to produce additional products. These medical effects may be expressed in crews as hypersensitivity, allergic, acute toxic, and chronic toxic reactions, as well as modifications of immune system response.

  2. Enhanced electrical and optical properties of iodine doped LDPE films

    NASA Astrophysics Data System (ADS)

    Sreelatha, K.; Predeep, P.

    2015-02-01

    In this study, an attempt has been made to dope Low Density Polyethylene (LDPE) with iodine and to study the effect of iodine doping on the optical band gap of LDPE films. The DC conductivity measurements and UV/Vis spectral studies are employed to characterize the samples. Iodine treatment induces colour change in the polymer film which supports the interaction between iodine molecules and polyethylene chains. I2 molecule links the polymer chains electronically and provides conducting path ways by forming DA complexes. The absorption band of complex films has extended to the visible and near infrared region of the spectrum. Further there are discernible shifts found in the energy gap and band edge towards lower energies on doping with iodine. This is essentially due to the formation of strong DA complexes upon iodine doping which improves the conducting behaviour.

  3. Laser induced fluorescence studies of iodine oxide chemistry. Part II. The reactions of IO with CH3O2, CF3O2 and O3.

    PubMed

    Dillon, Terry J; Tucceri, María E; Crowley, John N

    2006-11-28

    The technique of pulsed laser photolysis was coupled to laser induced fluorescence detection of iodine oxide (IO) to measure rate coefficients, k for the reactions IO + CH(3)O(2)--> products (R1, 30-318 Torr N(2)), IO + CF(3)O(2)--> products (R2, 70-80 Torr N(2)), and IO + O(3)--> OIO + O(2) (R3a). Values of k(1) = (2 +/- 1) x 10(-12) cm(3) molecule(-1) s(-1), k(2) = (3.6 +/- 0.8) x 10(-11) cm(3) molecule(-1) s(-1), and k(3a) <5 x 10(-16) cm(3) molecule(-1) s(-1) were obtained at T = 298 K. In the course of this work, the product yield of IO from the reaction of CH(3)O(2) with I was determined to be close to zero, whereas CH(3)OOI was formed efficiently at 70 Torr N(2). Similarly, no evidence was found for IO formation in the CF(3)O(2) + I reaction. An estimate of the rate coefficients k(CH(3)O(2) + I) = 2 x 10(-11) cm(3) molecule(-1) s(-1) and k(CH(3)OOI + I) = 1.5 x 10(-10) cm(3) molecule(-1) s(-1) was also obtained. The results on k(1)-k(3) are compared to the limited number of previous investigations and the implications for the chemistry of the marine boundary layer are briefly discussed.

  4. Deficiency of prolactin-inducible protein leads to impaired Th1 immune response and susceptibility to Leishmania major in mice.

    PubMed

    Li, Jintao; Liu, Dong; Mou, Zhirong; Ihedioha, Olivia C; Blanchard, Anne; Jia, Ping; Myal, Yvonne; Uzonna, Jude E

    2015-04-01

    Although the strategic production of prolactin-inducible protein (PIP) at several ports of pathogen entry into the body suggests it might play a role in host defense, no study has directly implicated it in immunity against any infectious agent. Here, we show for the first time that PIP deficiency is associated with reduced numbers of CD4(+) T cells in peripheral lymphoid tissues and impaired CD4(+) Th1-cell differentiation in vitro. In vivo, CD4(+) T cells from OVA-immunized, PIP-deficient mice showed significantly impaired proliferation and IFN-γ production following in vitro restimulation. Furthermore, PIP-deficient mice were highly susceptible to Leishmani major infection and failed to control lesion progression and parasite proliferation. This susceptibility was associated with impaired NO production and leishmanicidal activity of PIP KO macrophages following IFN-γ and LPS stimulation. Collectively, our findings implicate PIP as an important regulator of CD4(+) Th1-cell-mediated immunity.

  5. Deficiency of the Two-Pore-Domain Potassium (K2P) Channel TREK-1 Promotes Hyperoxia-Induced Lung Injury

    PubMed Central

    Schwingshackl, Andreas; Teng, Bin; Makena, Patrudu; Ghosh, Manik; Sinclair, Scott E.; Luellen, Charlean; Balasz, Louisa; Rovnaghi, Cynthia; Bryan, Robert M.; Lloyd, Eric E.; Fitzpatrick, Elizabeth; Saravia, Jordy S.; Cormier, Stephania A.; Waters, Christopher M.

    2014-01-01

    Objective We previously reported the expression of the 2-pore domain K+ channel TREK-1 in lung epithelial cells and proposed a role for this channel in the regulation of alveolar epithelial cytokine secretion. In this study we focused on investigating the role of TREK-1 in vivo in the development of hyperoxia-induced lung injury. Design Laboratory animal experiments. Setting University research laboratory. Subjects Wild type and TREK-1 deficient mice. Interventions Mice were anesthetized and exposed to 1) room air, no mechanical ventilation, 2) 95% hyperoxia for 24 hours, 3) 95% hyperoxia for 24 hours followed by mechanical ventilation for 4 hours. Measurements and Main Results Hyperoxia exposure accentuated lung injury in TREK-1 deficient mice but not controls, resulting in increased in Lung Injury Scores (LIS), broncho-alveolar lavage (BAL) fluid cell numbers and cellular apoptosis, and a decrease in quasi-static lung compliance. Exposure to a combination of hyperoxia and injurious mechanical ventilation resulted in further morphological lung damage, increased LIS and BAL fluid cell numbers in control but not TREK-1 deficient mice. At baseline and after hyperoxia exposure BAL cytokine levels were unchanged in TREK-1 deficient mice compared to controls. Exposure to hyperoxia and mechanical ventilation resulted in an increase in BAL IL-6, MCP-1 and TNF-α levels in both mouse types, but the increase in IL-6 and MCP-1 levels was less prominent in TREK-1 deficient mice than in controls. Lung tissue MIP-2, KC and IL-1β gene expression was not altered by hyperoxia in TREK-1 deficient mice compared to controls. Furthermore, we show for the first time TREK-1 expression on alveolar macrophages and unimpaired TNF-α secretion from TREK-1 deficient macrophages. Conclusion TREK-1 deficiency resulted in increased sensitivity of lungs to hyperoxia but this effect is less prominent if overwhelming injury is induced by the combination of hyperoxia and injurious mechanical

  6. Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice

    PubMed Central

    Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R.; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

    2011-01-01

    Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. PMID:22216345

  7. Ultraviolet-B induced hyperplasia and squamous cell carcinomas in the cornea of XPA-deficient mice.

    PubMed

    De Vries, A; Gorgels, T G; Berg, R J; Jansen, G H; Van Steeg, H

    1998-07-01

    In Xeroderma Pigmentosum (XP) patients, due to a defective repair of UV-induced DNA damage, neoplastic changes occur in sunlight-exposed areas of the skin and eyes. There are seven complementation groups in XP (XP-A to XP-G). Recently, we have generated XPA-deficient mice (group-A XP) by gene targeting in embryonic stem cells. In order to evaluate UV-B sensitivity, XPA-deficient mice (n = 20), wild type (n = 7) and heterozygous mice (n = 13) were exposed to low daily doses of UV-B for 14 weeks at a cumulative dose of 22 kj m-2 (250-400 nm). For a period of 32 weeks, the mice were checked twice a week for the development of pathology. The UV-B treatment induced eye abnormalities in the XPA-deficient mice. Initially, photophobia was noticed, followed by a loss of transparency of the cornea, eventually affecting nearly all XPA-deficient mice (19 out of 20). In 12 out of 19 mice, the pathology progressed to give eye protrusion. Histology of these eyes showed hyperplasia and squamous cell carcinomas of the corneal epithelium. No eye-lesions were found in control (wild-type and heterozygous) mice that were exposed to the same UV-B dose. The corneal abnormalities found in the XPA-deficient mice appear to be similar to those found in human XP patients. These results confirm the role of the functional XPA gene in protecting the cornea from pathology by UV-B irradiation. In addition, they suggest that the XPA-deficient mouse is a suitable animal model for the study of XPA ocular disorders. PMID:9702178

  8. Iodine Status in Pregnant Women, Lactating Mothers, and Newborns in an Area with More Than Two Decades of Successful Iodine Nutrition.

    PubMed

    Nazeri, Pantea; Zarghani, Najmeh Hamzavi; Mirmiran, Parvin; Hedayati, Mehdi; Mehrabi, Yadollah; Azizi, Fereidoun

    2016-07-01

    Pregnant women, lactating mothers, and their newborns constitute the target population for prevention and control of iodine deficiency. Hence, the aim of this study was to evaluate the iodine nutrition status among these vulnerable groups in an area with more than two decades of successful elimination of iodine deficiency. In this cross-sectional study conducted in health care centers of Tehran, 100 pregnant women and 84 lactating mothers and their newborn were randomly selected. Urinary iodine concentration and iodine content of salts were measured using the Sandell-Kolthoff and titration methods, respectively. Urinary iodine concentration <150 μg/L for pregnant women and <100 μg/L for lactating mothers and newborns was considered as iodine nutrition inadequacy, respectively. Median (interquartile range [IQR]) urinary iodine concentration (UIC) was 103 (59-155) μg/L in pregnant women, 77 (42-194) μg/L in lactating mothers, and 198 (84-260) μg/L in newborns. Median (IQR) iodine content of salt was 26 (21-30) ppm and 25 (18-28) ppm in pregnant women and lactating mothers, respectively (P = 0.462). Iodine content of salt was significantly correlated with UIC of pregnant women (r = 0.24, P = 0.019), but no correlation was found among lactating mothers (r = 0.12, P = 0.316). Neonatal UIC was significantly correlated with iodine content of salt consumed by their mothers (r = 0.49, P = 0.001). Despite suboptimal iodine status among subgroups of Tehranian pregnant and lactating women, iodine nutrition status of newborns was within optimal levels, which may be explained by a compensatory mechanism in the mammary glands.

  9. Glucose-induced production of recombinant proteins in Hansenula polymorpha mutants deficient in catabolite repression.

    PubMed

    Krasovska, Olena S; Stasyk, Olena G; Nahorny, Viktor O; Stasyk, Oleh V; Granovski, Nikolai; Kordium, Vitaliy A; Vozianov, Oleksandr F; Sibirny, Andriy A

    2007-07-01

    The most commonly used expression platform for production of recombinant proteins in the methylotrophic yeast Hansenula polymorpha relies on the strong and strictly regulated promoter from the gene encoding peroxisomal enzyme alcohol (or methanol) oxidase (P(MOX)). Expression from P(MOX) is induced by methanol and is partially derepressed in glycerol or xylose medium, whereas in the presence of hexoses, disaccharides or ethanol, it is repressed. The need for methanol for maximal induction of gene expression in large-scale fermentation is a significant drawback, as this compound is toxic, flammable, supports a slow growth rate and requires extensive aeration. We isolated H. polymorpha mutants deficient in glucose repression of P(MOX) due to an impaired HpGCR1 gene, and other yet unidentified secondary mutations. The mutants exhibited pronounced defects in P(MOX) regulation only by hexoses and xylose, but not by disaccharides or ethanol. With one of these mutant strains as hosts, we developed a modified two-carbon source mode expression platform that utilizes convenient sugar substrates for growth (sucrose) and induction of recombinant protein expression (glucose or xylose). We demonstrate efficient regulatable by sugar carbon sources expression of three recombinant proteins: a secreted glucose oxidase from the fungus Aspergillus niger, a secreted mini pro-insulin, and an intracellular hepatitis B virus surface antigen in these mutant hosts. The modified expression platform preserves the favorable regulatable nature of P(MOX) without methanol, making a convenient alternative to the traditional system. PMID:17163508

  10. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency.

    PubMed

    Roy, Marc; Leclerc, Daniel; Wu, Qing; Gupta, Sapna; Kruger, Warren D; Rozen, Rima

    2008-10-01

    Valproate (VPA) treatment in pregnancy leads to congenital anomalies, possibly by disrupting folate or homocysteine metabolism. Since methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate interconversion and homocysteine metabolism, we addressed the possibility that VPA might have different teratogenicity in Mthfr(+/+) and Mthfr(+/-) mice and that VPA might interfere with folate metabolism through MTHFR modulation. Mthfr(+/+) and Mthfr(+/-) pregnant mice were injected with VPA on gestational day 8.5; resorption rates and occurrence of neural tube defects (NTDs) were examined on gestational day 14.5. We also examined the effects of VPA on MTHFR expression in HepG2 cells and on MTHFR activity and homocysteine levels in mice. Mthfr(+/+) mice had increased resorption rates (36%) after VPA treatment, compared to saline treatment (10%), whereas resorption rates were similar in Mthfr(+/-) mice with the two treatments (25-27%). NTDs were only observed in one group (VPA-treated Mthfr(+/+)). In HepG2 cells, VPA increased MTHFR promoter activity and MTHFR mRNA and protein (2.5- and 3.7-fold, respectively). Consistent with cellular MTHFR upregulation by VPA, brain MTHFR enzyme activity was increased and plasma homocysteine was decreased in VPA-treated pregnant mice compared to saline-treated animals. These results underscore the importance of folate interconversion in VPA-induced teratogenicity, since VPA increases MTHFR expression and has lower teratogenic potential in MTHFR deficiency. PMID:18615588

  11. Calvarial cleidocraniodysplasia-like defects with ENU-induced Nell-1 deficiency.

    PubMed

    Zhang, Xinli; Ting, Kang; Pathmanathan, Dharmini; Ko, Theodore; Chen, Weiwei; Chen, Feng; Lee, Haofu; James, Aaron W; Siu, Ronald K; Shen, Jia; Culiat, Cymbeline T; Soo, Chia

    2012-01-01

    Nell-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. To further define Nell-1's role in craniofacial patterning, we characterized defects of the ENU-induced Nell-1-deficient (END) mice, focusing on both intramembranous and endochondral cranial bones. Results showed that calvarial bones of neonatal END mice were reduced in thickness and density, with a phenotype resembling calvarial cleidocraniodysplasia. In addition, a global reduction in osteoblast markers was observed, including reductions in Runx2, alkaline phosphatase, and osteocalcin. Remarkably, detailed analysis of endochondral bones showed dysplasia as well. The chondrocranium in the END mouse showed enrichment for early, proliferating Sox9⁺ chondrocytes, whereas in contrast markers of chondrocytes maturation were reduced. These data suggest that Nell-1 is an important growth factor for regulation of osteochondral differentiation, by regulating both Runx2 and Sox9 expression within the calvarium. In summary, Nell-1 is required for normal craniofacial membranous and endochondral skeletal development.

  12. Dose dependency of time of onset of radiation-induced growth hormone deficiency

    SciTech Connect

    Clayton, P.E.; Shalet, S.M. )

    1991-02-01

    Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis.

  13. XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury

    PubMed Central

    Toba, Hiroaki; Tomankova, Tereza; Wang, Yingchun; Bai, Xiaohui; Cho, Hae-Ra; Guan, Zhehong; Adeyi, Oyedele A.; Tian, Feng; Keshavjee, Shaf; Liu, Mingyao

    2016-01-01

    XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation and migration. Its physiological function in vivo is largely unknown. The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation. The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2. In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung. Macrophage infiltration was significantly elevated in the lung of KO mice. There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages. XB130 is expressed in alveolar type I and type II cells in the lung. The expression in these cells was significantly reduced after LPS challenge. XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability. PMID:27029000

  14. Muricidal suppression by chlorpheniramine and changes in brain levels following dietary-induced thiamine deficiency in rats.

    PubMed

    Onodera, K

    1987-01-01

    The effects of thiamine deficiency on pharmacological and pharmacokinetic activities of chlorpheniramine were investigated in rats. Chlorpheniramine (5-10 mg/kg) showed a dose-dependent suppressive effect on muricide induced by thiamine deficiency. The ED50 value for muricidal suppression at 1 hr was approximately 7.1 mg/kg (95% confidence limits, 5.4-9.3 mg/kg) after oral administration. Using a high-performance liquid chromatographic (HPLC) method, chlorpheniramine was detectable at 10 min in the blood and brain of rats. The present pharmacokinetic data suggest that chlorpheniramine can easily pass through the blood-brain barrier (B.B.B.) and enter the brain. It is stored therein and is later slowly released and excreted. In thiamine deficient rats, chlorpheniramine entered the brain in much higher concentrations than in normal and pair-fed rats, and significantly higher levels were maintained for a period of 1.5 hr. These results suggest that thiamine deficiency affects pharmacological and pharmacokinetic activities in rats, and support the view that there is a malfunction of the B.B.B. in thiamine deficient rats. These factors should be taken into consideration in clinical usage and dosage. PMID:3685155

  15. Iodine generator for reclaimed water purification

    NASA Technical Reports Server (NTRS)

    Wynveen, R. A.; Powell, J. D.; Schubert, F. H. (Inventor)

    1977-01-01

    The system disclosed is for controlling the iodine level in a water supply in a spacecraft. It includes an iodine accumulator which stores crystalline iodine, an electrochemical valve to control the input of iodine to the drinking water and an iodine dispenser. A pump dispenses fluid through the iodine dispenser and an iodine sensor to a potable water tank storage. The iodine sensor electronically detects the iodine level in the water, and through electronic means, produces a correction current control. The correction current control operates the electro-chemical iodine valve to release iodine from the iodine accumulator into the iodine dispenser.

  16. Erythrocyte alterations in praseodymium-induced lecithin:cholesterol acyltransferase (LCAT) deficiency in the rat: comparison with familial LCAT deficiency in man.

    PubMed

    Godin, D V; Frohlich, J

    1981-03-01

    The intravenous administration of praseodymium nitrate (PrN) to rats was associated with parallel decreases in plasma lecithin: cholesterol acyltransferase (LCAT) activity and erythrocyte osmotic fragility at low doses (20 and 40 mg/kg) while higher doses (80 mg/kg) resulted in increases in both. Erythrocyte membranes from rats with PrN-induced LCAT deficiency exhibited small increases in cholesterol content, but not other alterations (e.g., in phospholipid profiles and sulfhydryl group latency) which characterize erythrocytes in familial LCAT deficiency in man. The administration of PrN caused a time- and dose-dependent accumulation of praseodymium in liver with hepatic levels being substantially greater in animals given the high (protective) as compared with the low (toxic) doses of PrN. Hepatic levels of glutathione were not altered by PrN administration, but hexobarbital sleeping time was markedly prolonged in animals receiving a toxic dose of PrN. It is suggested that dose-dependent alterations in the subcellular distribution of praseodymium may explain the paradoxical pathophysiological effects of high and low doses of PrN.

  17. Deficiency of the Tumor Promoter Gene wip1 Induces Insulin Resistance

    PubMed Central

    Armata, Heather L.; Chamberland, Sally; Watts, Lauren; Ko, Hwi Jin; Lee, Yongjin; Jung, Dae Young; Kim, Jason K.

    2015-01-01

    Diabetes is a growing health care issue, and prediabetes has been established as a risk factor for type 2 diabetes. Prediabetes is characterized by deregulated glucose control, and elucidating pathways which govern this process is critical. We have identified the wild-type (WT) p53-inducible phosphatase (WIP1) phosphatase as a regulator of glucose homeostasis. Initial characterization of insulin signaling in WIP1 knockout (WIP1KO) murine embryo fibroblasts demonstrated reduced insulin-mediated Ak mouse transforming activation. In order to assess the role of WIP1 in glucose homeostasis, we performed metabolic analysis on mice on a low-fat chow diet (LFD) and high fat diet (HFD). We observed increased expression of proinflammatory cytokines in WIP1KO murine embryo fibroblasts, and WIP1KO mice fed a LFD and a HFD. WIP1KO mice exhibited glucose intolerance and insulin intolerance on a LFD and HFD. However, the effects of WIP1 deficiency cause different metabolic defects in mice on a LFD and a HFD. WIP1KO mice on a LFD develop hepatic insulin resistance, whereas this is not observed in HFD-fed mice. Mouse body weights and food consumption increase slightly over time in LFD-fed WT and WIP1KO mice. Leptin levels are increased in LFD-fed WIP1KO mice, compared with WT. In contrast, HFD-fed WIP1KO mice are resistant to HFD-induced obesity, have decreased levels of food consumption, and decreased leptin levels compared with HFD-WT mice. WIP1 has been shown to regulate the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, loss of which leads to increased inflammation. We propose that this increased inflammation triggers insulin resistance in WIP1KO mice on LFD and HFD. PMID:25379953

  18. Glutamic acid ameliorates estrogen deficiency-induced menopausal-like symptoms in ovariectomized mice.

    PubMed

    Han, Na-Ra; Kim, Hee-Yun; Yang, Woong Mo; Jeong, Hyun-Ja; Kim, Hyung-Min

    2015-09-01

    Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of γ-aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency-induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)-positive human osteoblast-like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER-β messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal-regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER-β mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells.

  19. NLRP3 Deficiency Reduces Macrophage Interleukin-10 Production and Enhances the Susceptibility to Doxorubicin-induced Cardiotoxicity

    PubMed Central

    Kobayashi, Motoi; Usui, Fumitake; Karasawa, Tadayoshi; Kawashima, Akira; Kimura, Hiroaki; Mizushina, Yoshiko; Shirasuna, Koumei; Mizukami, Hiroaki; Kasahara, Tadashi; Hasebe, Naoyuki; Takahashi, Masafumi

    2016-01-01

    NLRP3 inflammasomes recognize non-microbial danger signals and induce release of proinflammatory cytokine interleukin (IL)-1β, leading to sterile inflammation in cardiovascular disease. Because sterile inflammation is involved in doxorubicin (Dox)-induced cardiotoxicity, we investigated the role of NLRP3 inflammasomes in Dox-induced cardiotoxicity. Cardiac dysfunction and injury were induced by low-dose Dox (15 mg/kg) administration in NLRP3-deficient (NLRP3−/−) mice but not in wild-type (WT) and IL-1β−/− mice, indicating that NLRP3 deficiency enhanced the susceptibility to Dox-induced cardiotoxicity independent of IL-1β. Although the hearts of WT and NLRP3−/− mice showed no significant difference in inflammatory cell infiltration, macrophages were the predominant inflammatory cells in the hearts, and cardiac IL-10 production was decreased in Dox-treated NLRP3−/− mice. Bone marrow transplantation experiments showed that bone marrow-derived cells contributed to the exacerbation of Dox-induced cardiotoxicity in NLRP3−/− mice. In vitro experiments revealed that NLRP3 deficiency decreased IL-10 production in macrophages. Furthermore, adeno-associated virus-mediated IL-10 overexpression restored the exacerbation of cardiotoxicity in the NLRP3−/− mice. These results demonstrated that NLRP3 regulates macrophage IL-10 production and contributes to the pathophysiology of Dox-induced cardiotoxicity, which is independent of IL-1β. Our findings identify a novel role of NLRP3 and provided new insights into the mechanisms underlying Dox-induced cardiotoxicity. PMID:27225830

  20. Elevated Slit2 Activity Impairs VEGF-induced Angiogenesis and Tumor Neovascularization in EphA2-deficient Endothelium

    PubMed Central

    Youngblood, Victoria; Wang, Shan; Song, Wenqiang; Walter, Debra; Hwang, Yoonha; Chen, Jin; Brantley-Sieders, Dana M.

    2015-01-01

    Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited by tumors. Indeed, tumors upregulate pro-angiogenic molecules while simultaneously suppressing angiostatic pathways in order to recruit blood vessels for growth, survival, and metastatic spread. Understanding how cancers exploit pro- and anti-angiogenic signals is a key step in developing new, molecularly targeted anti-angiogenic therapies. While EphA2, a receptor tyrosine kinase (RTK), is required for vascular endothelial growth factor (VEGF)-induced angiogenesis, the mechanism through which these pathways intersect remains unclear. Slit2 expression is elevated in EphA2-deficient endothelium, and here it is reported that inhibiting Slit activity rescues VEGF-induced angiogenesis in cell culture and in vivo, as well as VEGF-dependent tumor angiogenesis, in EphA2-deficient endothelial cells and animals. Moreover, blocking Slit activity or Slit2 expression in EphA2-deficient endothelial cells restores VEGF-induced activation of Src and Rac, both of which are required for VEGF-mediated angiogenesis. These data suggest that EphA2 suppression of Slit2 expression and Slit angiostatic activity enables VEGF-induced angiogenesis in vitro and in vivo, providing a plausible mechanism for impaired endothelial responses to VEGF in the absence of EphA2 function. PMID:25504371

  1. ARYL HYDROCARBON RECEPTOR DEFICIENCY PROTECTS MICE FROM DIET-INDUCED ADIPOSITY AND METABOLIC DISORDERS THROUGH INCREASED ENERGY EXPENDITURE

    PubMed Central

    Zhang, Zhi-Ming; Jaeger, Cassie D.; Krager, Stacey L.; Bottum, Kathleen M.; Liu, Jianghua; Liao, Duan-Fang; Tischkau, Shelley A.

    2015-01-01

    BACKGROUND/OBJECTIVES Epidemics of obesity and diabetes are escalating. High-calorie/high-fat food is a major cause for these global health issues, but molecular mechanisms underlying high-fat, diet-induced obesity are still not well understood. The aryl hydrocarbon receptor (AhR), a transcription factor that acts as a xenobiotic sensor, mediates environmental toxicant-induced obesity, insulin resistance and development of diabetes. AhR also influences lipid metabolism and diet-induced obesity. The effects of AhR deficiency on diet-induced obesity, hepatic steatosis and insulin resistance were examined. METHODS : Male wild type (WT), AhR null (AhR−/−) and AhR heterozygote (AhR+/−) mice were fed a normal chow diet (NCD, 10% kcal from fat) or a high-fat diet (HFD, 60% kcal from fat) for up to 14 weeks. Adiposity, adipose and liver morphology, insulin signaling, metabolic parameters and gene profiles were assessed. RESULTS AhR deficiency protected against HFD-induced obesity, hepatic steatosis, insulin resistance and inflammation. Moreover, AhR deficiency preserved insulin signaling in major metabolic tissues. These protective effects result from a higher energy expenditure in AhR-deficient mice compared to WT. Levels of transcript for both the thermogenic gene, uncoupling protein 1 (Ucp1), in brown adipose tissue and mitochondrial β-oxidation genes in muscle were significantly higher in AhR−/− and AhR+/− mice compared to WT. CONCLUSIONS This work documents a physiologically relevant function for AhR in regulation of body weight, hepatic fat deposition, insulin sensitivity and energy expenditure under HFD exposure, suggesting that AhR signaling may be developed as a potential therapeutic target for treatment of obesity and metabolic disorders. PMID:25907315

  2. Developmental vitamin D (DVD) deficiency alters pup-retrieval but not isolation-induced pup ultrasonic vocalizations in the rat.

    PubMed

    Burne, Thomas H J; O'Loan, Jonathan; Splatt, Karisha; Alexander, Suzanne; McGrath, John J; Eyles, Darryl W

    2011-02-01

    Evidence from animal experiments now demonstrates that prenatal vitamin D levels influence brain development. The aims of this study were to examine isolation-induced pup ultrasonic vocalizations and maternal-infant interactions using a pup-retrieval test in developmental vitamin D (DVD) deficient and control rats. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. In two separate experiments we recorded ultrasonic vocalizations at 46KHz in isolated pups and we performed a pup-retrieval test on the day of birth. There was no significant effect of maternal diet on the calling rate of isolation-induced ultrasonic vocalizations by pups. We found that DVD-deficient dams retrieved their pups sooner than control dams and engaged in more pup directed activities (sniffing and carrying pups) and had a longer latency for self-grooming and rearing than control dams. We also assessed vitamin D related measures from a terminal blood sample immediately after the pup-retrieval test and found that DVD-deficient dams and pups had significantly lower levels of 25 OH D₃, 1,25 (OH)₂D₃ and phosphate, elevated levels of parathyroid hormone (PTH) but there was no significant effect of maternal diet on calcium levels. We speculate that the altered maternal-pup interactions identified in the DVD model may impact on early periods of brain development and behaviour. PMID:21059363

  3. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

    PubMed

    Diekman, Eugene F; van Weeghel, Michel; Wanders, Ronald J A; Visser, Gepke; Houten, Sander M

    2014-07-01

    Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondrial long-chain fatty acid β-oxidation (FAO). Patients with VLCAD deficiency may present with hypoglycemia, hepatomegaly, cardiomyopathy, and myopathy. Although several mouse models have been developed to aid in the study of the pathogenesis of long-chain FAO defects, the muscular phenotype is underexposed. To address the muscular phenotype, we used a newly developed mouse model on a mixed genetic background with a more severe defect in FAO (LCAD(-/-); VLCAD(+/-)) in addition to a validated mouse model (LCAD(-/-); VLCAD(+/+)) and compared them with wild-type (WT) mice. We found that both mouse models show a 20% reduction in energy expenditure (EE) and a 3-fold decrease in locomotor activity in the unfed state. In addition, we found a 1.7°C drop in body temperature in unfed LCAD(-/-); VLCAD(+/+) mice compared with WT body temperature. We conclude that food withdrawal-induced inactivity, hypothermia, and reduction in EE are novel phenotypes associated with FAO deficiency in mice. Unexpectedly, inactivity was not explained by rhabdomyolysis, but rather reflected the overall reduced capacity of these mice to generate heat. We suggest that mice are partly protected against the negative consequence of an FAO defect.-Diekman, E. F., van Weeghel, M., Wanders, R. J. A., Visser, G., Houten, S. M. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

  4. Gastrointestinal bleeding secondary to trimethoprim-sulfamethoxazole-induced vitamin K deficiency.

    PubMed

    Fotouhie, Azadeh; Desai, Hem; King, Skye; Parsa, Nour Alhoda

    2016-06-06

    There is a well-known association between vitamin K deficiency and haemorrhagic events including gastrointestinal bleeding. There is also a well-known association between both poor dietary intake of vitamin K and chronic antibiotic use and the development of vitamin K deficiency. Although the medical literature notes that cephalosporin antibiotics have a propensity to cause vitamin K deficiency due to the molecular structure of the medications and their ability to suppress the synthesis of clotting factors, there are other antibiotics that have also been implicated in the development of vitamin K deficiency. There are very few reports of trimethoprim/sulfamethoxazole causing vitamin K deficiency and further leading to bleeding episodes. We present such a case and discuss the risk factors leading to such complications.

  5. High β-cell mass prevents streptozotocin-induced diabetes in thioredoxin-interacting protein-deficient mice

    PubMed Central

    Masson, Elodie; Koren, Shlomit; Razik, Fathima; Goldberg, Howard; Kwan, Edwin P.; Sheu, Laura; Gaisano, Herbert Y.; Fantus, I. George

    2010-01-01

    Thioredoxin-interacting protein (TxNIP) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. Diabetic mice exhibit increased expression of TxNIP in pancreatic islets, and recent studies suggest that TxNIP is a proapoptotic factor in β-cells that may contribute to the development of diabetes. Here, we examined the role of TxNIP deficiency in vivo in the development of insulin-deficient diabetes and whether it impacted on pancreatic β-cell mass and/or insulin secretion. TxNIP-deficient (Hcb-19/TxNIP−/−) mice had lower baseline glycemia, higher circulating insulin concentrations, and higher total pancreatic insulin content and β-cell mass than control mice (C3H). Hcb-19/TxNIP−/− did not develop hyperglycemia when injected with standard multiple low doses of streptozotocin (STZ), in contrast to C3H controls. Surprisingly, although β-cell mass remained higher in Hcb-19/TxNIP−/− mice compared with C3H after STZ exposure, the relative decrease induced by STZ was as great or even greater in the TxNIP-deficient animals. Consistently, cultured pancreatic INS-1 cells transfected with small-interfering RNA against TxNIP were more sensitive to cell death induced by direct exposure to STZ or to the combination of inflammatory cytokines interleukin-1β, interferon-γ, and tumor necrosis factor-α. Furthermore, when corrected for insulin content, isolated pancreatic islets from TxNIP−/− mice exhibited reduced glucose-induced insulin secretion. These data indicate that TxNIP functions as a regulator of β-cell mass and influences insulin secretion. In conclusion, the relative resistance of TxNIP-deficient mice to STZ-induced diabetes appears to be because of an increase in β-cell mass. However, TxNIP deficiency is associated with sensitization to STZ- and cytokine-induced β-cell death, indicating complex regulatory roles of TxNIP under different physiological and pathological conditions. PMID

  6. Progesterone inhibits vascular remodeling and attenuates monocrotaline-induced pulmonary hypertension in estrogen-deficient rats.

    PubMed

    Tofovic, P S; Zhang, X; Petrusevska, G

    2009-07-01

    (Full text is available at http://www.manu.edu.mk/prilozi). Pulmonary arterial hypertension (PH) is predominantly a disease of young females. Yet, little is known regarding the effects of female sex hormones in PH. Female rats develop less severe PH compared to male rats, and ovariectomy (OVX) exacerbates PH. Although OVX rats treated with estradiol develop less severe disease, the role of progesterone in OVX-induced exacerbation of disease has not been examined. Progesterone was shown to dilate pulmonary vessels and to inhibit proliferation of endothelial and vascular smooth muscle cells. Therefore, we hypothesized that progesterone may confer protective effects in experimental PH. A total of 30 female rats were ovariectomized and OVX rats were randomly administered either saline (OVX-Control group, n = 7), monocrotaline (60mg/kg i.p.; OVX-MCT group; n = 12), or MCT plus progesterone (30microg/kg/h via osmotic minipumps; OVX-MCT+P group; n = 11). After 32 days animals were instrumented for in situ (open chest) measurements of right ventricle (RV) peak systolic (RVSP) and end diastolic (RVEDP) pressures, and tissue samples were obtained for morphometric and histological analysis. Administration of MCT elevated RVSP (22.2 +/- 1.1 vs. 46.7 +/- 2.4 mmHg) and RVEDP (1.51 +/- 0.86 vs. 11.9+/-2.2 mmHg), increased RV/left ventricle + septum (RV/LV+S) ratio (0.256 +/- 0.010 vs. 0.582 +/- 0.033, OVX vs. OVX-MCT), and induced media hypertrophy of small size pulmonary arteries. In ovariectomized pulmonary hypertensive rats, treatment with progesterone attenuated the severity of disease (OVX-MCT+P group: RVSP = 36.6 +/- 2.3 mmHg; RV/LV+S = 0.468 +/- 0.025; RVEDP = 7.5 +/-1.5 mmHg), attenuated vascular remodeling (media % index: 28.2 +/- 1.1 vs. 34.2 +/- 1.3), and reduced mortality (9% vs. 25%; OVX-MCT+P vs. OVX-MCT). This study provides the first evidence that in estrogen-deficient rats, progesterone has protective effects in MCT-induced PH. Further evaluation of the role of

  7. TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver

    PubMed Central

    Weber, Susanne Nicole; Bohner, Annika; Dapito, Dianne H.; Schwabe, Robert F.; Lammert, Frank

    2016-01-01

    Background The development of hepatocellular carcinoma (HCC) is a common consequence of advanced liver fibrosis but the interactions between fibrogenesis and carcinogenesis are still poorly understood. Recently it has been shown that HCC promotion depends on Toll-like receptor (TLR) 4. Pre-cancerogenous events can be modelled in mice by the administration of a single dose of diethylnitrosamine (DEN), with HCC formation depending amongst others on interleukin (IL) 6 production. Mice lacking the hepatocanalicular phosphatidylcholine transporter ABCB4 develop liver fibrosis spontaneously, resemble patients with sclerosing cholangitis due to mutations of the orthologous human gene, and represent a valid model to study tumour formation in pre-injured cholestatic liver. The aim of this study was to investigate DEN-induced liver injury in TLR4-deficient mice with biliary fibrosis. Methods ABCB4-deficient mice on the FVB/NJ genetic background were crossed to two distinct genetic backgrounds (TLR4-sufficient C3H/HeN and TLR4-deficient C3H/HeJ) for more than 10 generations. The two congenic knockout and the two corresponding wild-type mouse lines were treated with a single dose of DEN for 48 hours. Phenotypic differences were assessed by measuring hepatic collagen contents, inflammatory markers (ALT, CRP, IL6) as well as hepatic apoptosis (TUNEL) and proliferation (Ki67) rates. Results Hepatic collagen accumulation is significantly reduced in ABCB4-/-:TLR4-/-double-deficient mice. After DEN challenge, apoptosis, proliferation and inflammatory markers are decreased in TLR4-deficient in comparison to TLR4-sufficient mice. When combining ABCB4 and TLR4 deficiency with DEN treatment, hepatic IL6 expression and proliferation rates are lowest in fibrotic livers from the double-deficient line. Consistent with these effects, selective digestive tract decontamination in ABCB4-/- mice also led to reduced tumor size and number after DEN. Conclusion This study demonstrates that liver

  8. Protein profile of Beta vulgaris leaf apoplastic fluid and changes induced by Fe deficiency and Fe resupply

    PubMed Central

    Ceballos-Laita, Laura; Gutierrez-Carbonell, Elain; Lattanzio, Giuseppe; Vázquez, Saul; Contreras-Moreira, Bruno; Abadía, Anunciación; Abadía, Javier; López-Millán, Ana-Flor

    2015-01-01

    The fluid collected by direct leaf centrifugation has been used to study the proteome of the sugar beet apoplastic fluid as well as the changes induced by Fe deficiency and Fe resupply to Fe-deficient plants in the protein profile. Plants were grown in Fe-sufficient and Fe-deficient conditions, and Fe resupply was carried out with 45 μM Fe(III)-EDTA for 24 h. Protein extracts of leaf apoplastic fluid were analyzed by two-dimensional isoelectric focusing-SDS-PAGE electrophoresis. Gel image analysis revealed 203 consistent spots, and proteins in 81% of them (164) were identified by nLC-MS/MS using a custom made reference repository of beet protein sequences. When redundant UniProt entries were deleted, a non-redundant leaf apoplastic proteome consisting of 109 proteins was obtained. TargetP and SecretomeP algorithms predicted that 63% of them were secretory proteins. Functional classification of the non-redundant proteins indicated that stress and defense, protein metabolism, cell wall and C metabolism accounted for approximately 75% of the identified proteome. The effects of Fe-deficiency on the leaf apoplast proteome were limited, with only five spots (2.5%) changing in relative abundance, thus suggesting that protein homeostasis in the leaf apoplast fluid is well-maintained upon Fe shortage. The identification of three chitinase isoforms among proteins increasing in relative abundance with Fe-deficiency suggests that one of the few effects of Fe deficiency in the leaf apoplast proteome includes cell wall modifications. Iron resupply to Fe deficient plants changed the relative abundance of 16 spots when compared to either Fe-sufficient or Fe-deficient samples. Proteins identified in these spots can be broadly classified as those responding to Fe-resupply, which included defense and cell wall related proteins, and non-responsive, which are mainly protein metabolism related proteins and whose changes in relative abundance followed the same trend as with Fe-deficiency

  9. Assessment of IDD problem by estimation of urinary iodine among school children.

    PubMed

    Joshi, Anand Ballabh; Banjara, Megha Raj; Bhatta, Lok Ranjan; Rikimaru, Toru; Jimba, Masamine

    2006-06-01

    Iodine deficiency disorder (IDD) is a major micronutrient deficiency problem in Nepal. Urinary iodine estimation has been the gold standard employed for the assessment of iodine status and of IDD. This study was conducted with objective to assess the urinary iodine among the school children of Kavre, Lalitpur and Parsa districts. Attempts were made to relate urinary iodine with salt use and other sociodemographic variables. Altogether 190 urine samples (74 samples from Kavre, 89 from Parsa and 27 from Lalitpur district) were collected from school children aged 5-13 years. The urinary iodine was analyzed by using urinary iodine assay kit (Bioclone Australia Pvt Limited). It was found that 3.2% children had urine iodine concentration below 20 microg/l. Similarly, the percentage of children with urine iodine concentration 21-50 microg/l, 51-99 microg/l, 100-299 microg/l and above 300 microg/l were 14.2%, 10.5%, 43.7% and 28.4% respectively. Iodine deficient population of school children was 39.2% of Kavre, 19.1% of Parsa and 25.9% of Lalitpur. Overall, it was found that 27.9% children had urine iodine level less than the normal WHO levels. The median urine iodine level was 139.0 microg/l of Kavre, 266.7 microg/l of Parsa and 244.4 microg/l of Lalitpur school children. Urinary iodine excretion (UIE) median value among male students was 211.9 microg/l, among female students was 190.2 microg/l and the difference was statistically insignificant (P > 0.05). There was no significant correlation between consumed salt iodine level and urine iodine excretion level (P > 0.05). Short-term iodine supplementation programs should be arranged for iodine deficient children in the study districts. This study shows that IDD continues to be prevalent in the country as a major public health problem, which requires strengthening effective intervention program and other preventive measures.

  10. Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4 deficient mice

    PubMed Central

    Ji, Yewei; Sun, Shengyi; Goodrich, Julia K.; Kim, Hana; Poole, Angela C.; Duhamel, Gerald E.; Ley, Ruth E.; Qi, Ling

    2014-01-01

    SUMMARY Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here we show that chronic intake of a high-fat diet (HFD), not a low-fat diet (LFD), leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors (TLR) 2 and 4 (DKO hereafter). Diet-induced pulmonary lesions are blocked by antibiotics treatment and transmissible to wildtype mice upon either cohousing or fecal transplantation, pointing to the existence of bacterial pathogens. Indeed, diet and innate deficiency exert significant impact on gut microbiota composition. Thus, chronic intake of HFD promotes severe pulmonary damage and mortality in DKO mice in part via gut dysbiosis, a finding that may be important for immunodeficient patients, particularly those on chemotherapy or radiotherapy, where gut microbiota-caused conditions are often life-threatening. PMID:24953658

  11. Group IVA phospholipase A(2) deficiency prevents CCl4-induced hepatic cell death through the enhancement of autophagy.

    PubMed

    Ishihara, Keiichi; Kanai, Shiho; Tanaka, Kikuko; Kawashita, Eri; Akiba, Satoshi

    2016-02-26

    Group IVA phospholipase A2 (IVA-PLA2), which generates arachidonate, plays a role in inflammation. IVA-PLA2-deficiency reduced hepatotoxicity and hepatocyte cell death in mice that received a single dose of carbon tetrachloride (CCl4) without any inhibitory effects on CCl4-induced lipid peroxidation. An immunoblot analysis of extracts from wild-type mouse- and IVA-PLA2 KO mouse-derived primary hepatocytes that transiently expressed microtubule-associated protein 1 light chain 3B (LC3) revealed a higher amount of LC3-II, a typical index of autophagosome formation, in IVA-PLA2-deficient cells, suggesting the enhancement of constitutive autophagy. IVA-PLA2 may promote CCl4-induced cell death through the suppression of constitutive autophagy in hepatocytes.

  12. Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4-deficient mice.

    PubMed

    Ji, Yewei; Sun, Shengyi; Goodrich, Julia K; Kim, Hana; Poole, Angela C; Duhamel, Gerald E; Ley, Ruth E; Qi, Ling

    2014-07-10

    Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here, we show that chronic intake of a high-fat diet (HFD), not a low-fat diet, leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors 2 and 4 (DKO). Diet-induced pulmonary lesions are blocked by antibiotic treatment and are transmissible to wild-type mice upon either cohousing or fecal transplantation, pointing to the existence of bacterial pathogens. Indeed, diet and innate deficiency exert significant impact on gut microbiota composition. Thus, chronic intake of HFD promotes severe pulmonary damage and mortality in DKO mice in part via gut dysbiosis, a finding that may be important for immunodeficient patients, particularly those on chemotherapy or radiotherapy, where gut-microbiota-caused conditions are often life threatening.

  13. Characterization of MxFIT, an iron deficiency induced transcriptional factor in Malus xiaojinensis.

    PubMed

    Yin, Lili; Wang, Yi; Yuan, Mudan; Zhang, Xinzhong; Xu, Xuefeng; Han, Zhenhai

    2014-02-01

    Iron deficiency often results in nutritional disorder in fruit trees. Transcription factors play an important role in the regulation of iron uptake. In this study, we isolated an iron deficiency response transcription factor gene, MxFIT, from an iron-efficient apple genotype of Malus xiaojinensis. MxFIT encoded a basic helix-loop-helix protein and contained a 966 bp open reading frame. MxFIT protein was targeted to the nucleus in onion epidermal cells and showed strong transcriptional activation in yeast cells. Spatiotemporal expression analysis revealed that MxFIT was up-regulated in roots under iron deficiency at both mRNA and protein levels, while almost no expression was detected in leaves irrespective of iron supply. Ectopic expression of MxFIT resulted in enhanced iron deficiency responses in Arabidopsis under iron deficiency and stronger resistance to iron deficiency. Thus, MxFIT might be involved in iron uptake and plays an important role in iron deficiency response.

  14. Induced genetic deficiency of the nucleolar organizer in rat kangaroo cells (PTK1) by ultraviolet laser microirradiation.

    PubMed

    Liang, H; Berns, M W

    1983-03-01

    An ultraviolet laser microbeam was used to irradiate one of the two nucleolar organizer regions of PTK1 cells in early prophase. The directed nucleolar deficiency induced by ultraviolet laser irradiation was maintained in the daughter cells through subsequent cell generations. However, the frequent occurrence of spontaneous cell fusion in low density cells following the cloning procedure facilitated a recovery of cells to two or more nucleoli.

  15. Programmed cell death of T lymphocytes during acute viral infection: a mechanism for virus-induced immune deficiency.

    PubMed Central

    Razvi, E S; Welsh, R M

    1993-01-01

    Acute viral infections induce immune deficiencies, as shown by unresponsiveness to mitogens and unrelated antigens. T lymphocytes isolated from mice acutely infected with lymphocytic choriomeningitis virus (LCMV) were found in this study to undergo activation-induced apoptosis upon signalling through the T-cell receptor (TcR)-CD3 complex. Kinetic studies demonstrated that this sensitivity to apoptosis directly correlated with the induction of immune deficiency, as measured by impaired proliferation in response to anti-CD3 antibody or to concanavalin A. Cell cycling in interleukin-2 (IL-2) alone stimulated proliferation of LCMV-induced T cells without inducing apoptosis, but preculturing of T cells from acutely infected mice in IL-2 accelerated apoptosis upon subsequent TcR-CD3 cross-linking. T lymphocytes isolated from mice after the acute infection were less responsive to IL-2, but those T cells, presumably memory T cells, responding to IL-2 were primed in each case to die a rapid apoptotic death upon TcR-CD3 cross-linking. These results indicate that virus infection-induced unresponsiveness to T-cell mitogens is due to apoptosis of the activated lymphocytes and suggest that the sensitization of memory cells by IL-2 induced during infection will cause them to die upon antigen recognition, thereby impairing specific responses to nonviral antigens. Images PMID:8371341

  16. TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4

    PubMed Central

    Abston, Eric D.; Coronado, Michael J.; Bucek, Adriana; Onyimba, Jennifer A.; Brandt, Jessica E.; Frisancho, J. Augusto; Kim, Eunyong; Bedja, Djahida; Sung, Yoon-kyu; Radtke, Andrea J.; Gabrielson, Kathleen L.; Mitzner, Wayne

    2013-01-01

    Recent findings indicate that TLR3 polymorphisms increase susceptibility to enteroviral myocarditis and inflammatory dilated cardiomyopathy (iDCM) in patients. TLR3 signaling has been found to inhibit coxsackievirus B3 (CVB3) replication and acute myocarditis in mouse models, but its role in the progression from myocarditis to iDCM has not been previously investigated. In this study we found that TLR3 deficiency increased acute (P = 5.9 × 10−9) and chronic (P = 6.0 × 10−7) myocarditis compared with WT B6.129, a mouse strain that is resistant to chronic myocarditis and iDCM. Using left ventricular in vivo hemodynamic assessment, we found that TLR3-deficient mice developed progressively worse chronic cardiomyopathy. TLR3 deficiency significantly increased viral replication in the heart during acute myocarditis from day 3 through day 12 after infection, but infectious virus was not detected in the heart during chronic disease. TLR3 deficiency increased cytokines associated with a T helper (Th)2 response, including IL-4 (P = 0.03), IL-10 (P = 0.008), IL-13 (P = 0.002), and TGF-β1 (P = 0.005), and induced a shift to an immunoregulatory phenotype in the heart. However, IL-4-deficient mice had improved heart function during acute CVB3 myocarditis by echocardiography and in vivo hemodynamic assessment compared with wild-type mice, indicating that IL-4 impairs cardiac function during myocarditis. IL-4 deficiency increased regulatory T-cell and macrophage populations, including FoxP3+ T cells (P = 0.005) and Tim-3+ macrophages (P = 0.004). Thus, TLR3 prevents the progression from myocarditis to iDCM following CVB3 infection by reducing acute viral replication and IL-4 levels in the heart. PMID:23255589

  17. Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y gene expression induced by zinc deficiency in the rat.

    PubMed

    Selvais, P L; Labuche, C; Nguyen, X N; Ketelslegers, J M; Denef, J F; Maiter, D M

    1997-01-01

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