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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. PMID:24753110

  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 induces a VEGF-dependent microvascular response in salivary glands and in the stomach.

    PubMed

    Vanderstraeten, Jessica; Derradji, Hanane; Craps, Julie; Sonveaux, Pierre; Colin, Ides M; Many, Marie-Christine; Gérard, Anne-Catherine

    2016-08-01

    Despite efforts to optimize iodine supply in iodine deficient countries, iodine deficiency (ID) remains a global problem worldwide. Activation of the local microvasculature by ID in the thyroid gland aims at improving the local supply of iodide. For this purpose, the thyrocytes secrete vascular endothelial growth factor (VEGF) that acts on adjacent capillaries, via a reactive oxygen species (ROS)/Hypoxia Inducible factor (HIF)-dependent pathway. Beside the thyroid, other organs including salivary glands and the stomach do express the sodium/iodide symporter (NIS) and are able to take iodide up, potentially rendering them sensitive to ID. To verify this hypothesis, ID-induced effects on the local microvasculature were studied in salivary glands and in the stomach. ID was induced by feeding young mice with an iodide-deficient diet and NIS inhibitor perchlorate in the drinking water. In salivary glands, ID induced a transient increase in HIF-1α protein expression accompanied by a transient, VEGF-dependent increase in blood flow. In the gastric mucosa, ID transiently increased VEGF expression in the mucin-secreting epithelium and in ghrelin-secreting endocrine cells. These observations suggest that microvascular changes in response to ID occur in NIS-expressing tissues other than the thyroid. NIS expressing cells could be viewed as iodide sensors that respond to ID by inducing vascular changes, probably to optimize iodide bioavailability at regional or systemic levels. PMID:26838679

  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 disorders in Europe.

    PubMed Central

    Delange, F.; Bürgi, H.

    1989-01-01

    Recent data on iodine excretion in the urine of adults, adolescents and newborns and on the iodine content of breast milk indicate a high prevalence of iodine deficiency (moderate in many cases and severe in a few) in many European countries. These cases may manifest as subclinical hypothyroidism in neonates and as goitre in adolescents and adults. Lack of iodine causes not only goitre, but also mental deficiency, hearing loss and other neurological impairments, and short stature due to thyroid insufficiency during fetal development and childhood. Although iodinated salt is available theoretically in most countries where it is needed, its quality and share of the market are often unsatisfactory. In many countries where only household salt is iodinated the iodine content has been set too low owing to an overestimation of household salt consumption. Governments are therefore urged to pass legislation and provide means for efficient iodination of salt wherever this is necessary. PMID:2670299

  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. [Physiopathology of iodine deficiency].

    PubMed

    Pinchera, A; Rago, T; Vitti, P

    1998-01-01

    The process of goitrogenesis is likely to be the consequence of an increased TSH stimulation linked to an initial reduction of circulating thyroid hormone caused by iodine deficiency (ID). Other growth factors associated to TSH may have a role in the pathogenesis of goiter. Natural history of goiter is the evolution towards nodularity and functional autonomy. This phenomenon is due to the heterogeneity of thyroid follicular cells, some of which, with an intrinsic elevated growth rate, under the stimulation of ID progress to nodule formation and hyperfunction. In multinodular goiter TSH receptor mutations activating adenylate cyclase-cAMP pathway were found. In a recent epidemiological survey it was shown that nodular goiter increased with the age, being about 1% in schoolchildren and 23% in the adults (56-75 years). Also nodular autonomy and hyperthyroidism were more frequent in the 36-75 year age group. Severe ID is also cause of endemic cretinism. In Europe minor neuropsychological impairments and cognitive deficits were described in areas of moderate ID. The exposure to a mild ID during fetal life causes minor neuropsychological damage. In conclusion, ID is responsible of goiter and its evolution towards nodularity and functional autonomy. Severe ID is also cause of endemic cretinism, while cognitive deficits and minor neuropsychological impairments were found in mild to moderate ID. PMID:10052165

  10. Iodine deficiency disorders in Bangladesh.

    PubMed

    Yusuf, H K; Quazi, S; Kahn, M R; Mohiduzzaman, M; Nahar, B; Rahman, M M; Islam, M N; Khan, M A; Shahidullah, M; Hoque, T; Baquer, M; Pandav, C S

    1996-01-01

    An extensive iodine deficiency disorders survey was conducted in Bangladesh in 1993 to assess the latest iodine nutriture status of the country. The clinical variables of the survey were goitre and cretinism, and the biochemical variable was urinary iodine. The "EPI-30 cluster" sampling methodology was followed for selecting the survey sites. In each survey site, the study population consisted of boys and girls, aged 5-11 years, and men and women, aged 15-44 years, in about equal populations. The total number of survey sites was 78 and the total number of respondents was 30,072. The total number of urine samples was 4512 (15% sub-sample). The current total goitre rate (grade 1 + grade 2) in Bangladesh is 47.1% (hilly, 44.4%; flood-prone, 50.7%; and plains, 45.6%). The prevalence of cretinism in the country is 0.5% (hilly, 0.8%; flood-prone, 0.5%; and plains, 0.3%). Nearly 69% of Bangladeshi population have biochemical iodine deficiency (urinary iodine excretion [UIE] < 10 mg/dl) (hilly, 84.4; flood-prone, 67.1%; and plains 60.4%). Women and children are more affected that men, in terms of both goitre prevalence and UIE. The widespread severe iodine deficiency in all ecological zones indicates that the country as a whole is an iodine-deficient region. Important recommendations of global interest are made from the experience of the survey. PMID:10829973

  11. 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

  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 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

  14. [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

  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. PMID:8427203

  16. 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

  17. Involvement of mTOR and Regulation by AMPK in Early Iodine Deficiency-Induced Thyroid Microvascular Activation.

    PubMed

    Craps, J; Joris, V; De Jongh, B; Sonveaux, P; Horman, S; Lengelé, B; Bertrand, L; Many, M-C; Colin, I M; Gérard, A-C

    2016-06-01

    Iodine deficiency (ID) induces TSH-independent microvascular activation in the thyroid via the reactive oxygen species/nitric oxide-hypoxia-inducible factor-1α/vascular endothelial growth factor (VEGF) pathway. We hypothesized the additional involvement of mammalian target of rapamycin (mTOR) as a positive regulator of this pathway and AMP-activated protein kinase (AMPK) as a negative feedback regulator to explain the transient nature of ID-induced microvascular changes under nonmalignant conditions. mTOR and AMPK involvement was investigated using an in vitro model (human thyrocytes in primary cultures) and 2 murine models of goitrogenesis (normal NMRI and RET-PTC mice [a papillary thyroid cancer model]). In NMRI mice, ID had no effect on the phosphorylation of ribosomal S6 kinase (p70S6K), a downstream target of mTOR. However, rapamycin inhibited ID-induced thyroid blood flow and VEGF protein expression. In the RET-PTC model, ID strongly increased the phosphorylation of p70S6K, whereas rapamycin completely inhibited the ID-induced increase in p70S6K phosphorylation, thyroid blood flow, and VEGF-A expression. In vitro, although ID increased p70S6K phosphorylation, the ID-stimulated hypoxia-inducible factor/VEGF pathway was inhibited by rapamycin. Activation of AMPK by metformin inhibited ID effects both in vivo and in vitro. In AMPK-α1 knockout mice, the ID-induced increase in thyroid blood flow and VEGF-A protein expression persisted throughout the treatment, whereas both parameters returned to control values in wild-type mice after 4 days of ID. In conclusion, mTOR is required for early ID-induced thyroid microvascular activation. AMPK negatively regulates this pathway, which may account for the transient nature of ID-induced TSH-independent vascular effects under benign conditions. PMID:27035650

  18. 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

  19. 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

  20. 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

  1. Iodine content of infant formulas and iodine intake of premature babies: high risk of iodine deficiency.

    PubMed

    Ares, S; Quero, J; Durán, S; Presas, M J; Herruzo, R; Morreale de Escobar, G

    1994-11-01

    As part of a study of thyroid function in premature babies, the iodine content of their mothers' breast milk, that of 32 formulas from different brands used in Spain, and that of 127 formulas used in other countries was determined. Breast milk contained more iodine--mean (SEM) 10 (1) microgram/dl--than most of the formulas, especially those for premature babies. Iodine intakes were therefore below the recommended daily amount (RDA) for newborns: babies of 27-30 weeks' gestational age took 3.1 (1.1) micrograms/day at 5 days of age and 29.8 (2.7) micrograms by 2 months of age. This problem is not exclusive to Spanish premature babies as the iodine content of many of the formulas on sale in other countries was also inadequate. It is concluded that preterm infants who are formula fed are at high risk of iodine deficiency. PMID:7820714

  2. Iodine content of infant formulas and iodine intake of premature babies: high risk of iodine deficiency.

    PubMed Central

    Ares, S; Quero, J; Durán, S; Presas, M J; Herruzo, R; Morreale de Escobar, G

    1994-01-01

    As part of a study of thyroid function in premature babies, the iodine content of their mothers' breast milk, that of 32 formulas from different brands used in Spain, and that of 127 formulas used in other countries was determined. Breast milk contained more iodine--mean (SEM) 10 (1) microgram/dl--than most of the formulas, especially those for premature babies. Iodine intakes were therefore below the recommended daily amount (RDA) for newborns: babies of 27-30 weeks' gestational age took 3.1 (1.1) micrograms/day at 5 days of age and 29.8 (2.7) micrograms by 2 months of age. This problem is not exclusive to Spanish premature babies as the iodine content of many of the formulas on sale in other countries was also inadequate. It is concluded that preterm infants who are formula fed are at high risk of iodine deficiency. PMID:7820714

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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…

  8. 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

  9. 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

  10. [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

  11. Iodine-deficient vegetarians: a hypothetical perchlorate-susceptible population?

    PubMed

    Fields, Cheryl; Dourson, Michael; Borak, Jonathan

    2005-06-01

    Recent risk assessments of environmental perchlorate have been subject to much debate. A particular concern is whether appropriate susceptible sub-populations have been identified. Iodine-deficient pregnant women, especially vegetarians, have been proposed as such a potential susceptible sub-population, but there is no evidence of iodine deficiency in the US population and the adequacy of iodine nutrition has not been studied in US vegetarians. To understand the possibility that US vegetarians might be iodine deficient, we reviewed the prevalence, demography, and lifestyle characteristics of US vegetarians as well as the world literature on iodine nutrition in vegetarians. Our findings indicate that strict vegetarians and vegans, who comprise probably less than 0.1% of the US population, have higher education, higher incomes, and healthier lifestyles than the general population. Field studies indicate that vegetarian diets need not lead to iodine deficiency and vegans may suffer excess iodine intake. It is remains uncertain whether there are iodine-deficient vegans or pregnant women in the US. Of more general concern is whether the 10-fold default uncertainty factor is needed for intraspecies (i.e., within human) variability to protect such hypothetical susceptible sub-populations. PMID:15896441

  12. Involvement of nitric oxide in iodine deficiency-induced microvascular remodeling in the thyroid gland: role of nitric oxide synthase 3 and ryanodine receptors.

    PubMed

    Craps, J; Wilvers, C; Joris, V; De Jongh, B; Vanderstraeten, J; Lobysheva, I; Balligand, J-L; Sonveaux, P; Gilon, P; Many, M-C; Gérard, A-C; Colin, I M

    2015-02-01

    Iodine deficiency (ID) induces microvascular changes in the thyroid gland via a TSH-independent reactive oxygen species-hypoxia inducible factor (HIF)-1α-vascular endothelial growth factor (VEGF) pathway. The involvement of nitric oxide (NO) in this pathway and the role of calcium (Ca(2+)) and of ryanodine receptors (RYRs) in NO synthase 3 (NOS3) activation were investigated in a murine model of goitrogenesis and in 3 in vitro models of ID, including primary cultures of human thyrocytes. ID activated NOS3 and the production of NO in thyrocytes in vitro and increased the thyroid blood flow in vivo. Using bevacizumab (a blocking antibody against VEGF-A) in mice, it appeared that NOS3 is activated upstream of VEGF-A. L-nitroarginine methyl ester (a NOS inhibitor) blocked the ID-induced increase in thyroid blood flow in vivo and NO production in vitro, as well as ID-induced VEGF-A mRNA and HIF-1α expression in vitro, whereas S-nitroso-acetyl-penicillamine (a NO donor) did the opposite. Ca(2+) is involved in this pathway as intracellular Ca(2+) flux increased after ID, and thapsigargin activated NOS3 and increased VEGF-A mRNA expression. Two of the 3 known mammalian RYR isoforms (RYR1 and RYR2) were shown to be expressed in thyrocytes. RYR inhibition using ryanodine at 10μM decreased ID-induced NOS3 activation, HIF-1α, and VEGF-A expression, whereas RYR activation with ryanodine at 1nM increased NOS3 activation and VEGF-A mRNA expression. In conclusion, during the early phase of TSH-independent ID-induced microvascular activation, ID sequentially activates RYRs and NOS3, thereby supporting ID-induced activation of the NO/HIF-1α/VEGF-A pathway in thyrocytes. PMID:25406019

  13. [Iodine deficiency in pregnancy--a continuing public health problem].

    PubMed

    Szybiński, Zbigniew

    2005-01-01

    Iodine prophylaxis in Poland started in 1997 and is based on mandatory iodzation of household salt with 20-40 mg KI/ 1 kg, supplementation of bottle fed infants with iodized formulas with 10,0 microg KI/100 ml, and a voluntary supplementation of pregnant and breast feeding women with additional 100-150 microg of iodine/ day. Last evaluation of efficacy of the iodine prophylaxis performed in 2003 by WHO and International Council for the Control of Iodine Deficiency Disorders allocated Poland within the group of the European countries with sufficient iodine supplementation on the population level. However according to data of the Institute of Mather and Chield in Poland, around 50 % of pregnant women only is additionally supplemented with iodine. Iodine deficiency during pregnancy even as a moderate iodine deficiency, creates a risk of mental retardation, perinatal complication like low and very low births weigt of neonates with increased perinatal mortality rate and late consequences in adult life: metabolic syndrom and type 2 diabetes. Another limitation of the actual model of iodine prophylaxis in Poland, it is too high consumption of natrum chloride (over 5,0 g of household salt/day/ capita). It is around 50% over WHO recommendation. Intensive preventive program against hypertension, type 2 diabetes, atherosclerosis, osteoporosis and some neoplasmatic diseases includes limitation of natrum chloride consumption- as one of the risk factors. Therefore new scope of the National Programme for Elimination of Iodine Deficiency will include: a special prorgramme for the iodization of animal food according to european standard, increased rate of pregnant women additionally supplemented with iodine, strengthening public awarness on necessary increase of milk consumption especially in pregnancy and in children and continouse monitoring system of biologic effects and technologic quality of the model of iodine prophylaxis. PMID:16335675

  14. 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 ...

  15. [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

  16. National Iodine Deficiency Disorders Control Programme in India.

    PubMed

    Tiwari, B K; Kundu, A K; Bansal, R D

    1995-01-01

    Iodine Deficiency Disorders are one of the biggest worldwide public health problem of today. Their effect is hidden and profound affecting the quality of human life. An attempt has been made to describe the various aspects of the National Iodine Deficiency Disorders control Programme (NIDDCP) being implemented in the country. The paper also focuses about the problems associated in implementing this national programme. PMID:8690502

  17. 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.

  18. 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

  19. 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

  20. Assessment of goiter in an area of endemic iodine deficiency.

    PubMed

    Smyth, P P; Darke, C; Parkes, A B; Smith, D F; John, R; Hetherton, A M; Lazarus, J H

    1999-09-01

    Urinary iodone (UI) excretion and sonographically measured thyroid volume were investigated in 195 subjects living in 6 separate villages in the Casamance region of southeastern Senegal, West Africa. A comparison of goiter prevalence using thyroid palpation and volume measurement and of iodine excretion expressed as micrograms per gram (microg/g) creatinine or micrograms per deciliter (microg/dl) urine was undertaken, and possible pathogenetic factors were investigated. Ultrasound measured thyroid volumes were above the recommended upper limit of the reference range for an area replete in iodine in 83.1% or females, 52.3% of males, and 80.0% of children aged 13 years or younger. Overall sensitivity and specificity for palpation compared to sonographically demonstrated thyroid enlargement was 51.7% and 91.5%, respectively. Thyroid enlargement was not associated with ethnic origin, thiocyanate ingestion, HLA DR/DQ phenotype frequency, or thyroid growth-stimulating immunoglobulin (TGI) positivity. Median UI was 32 microg/g creatinine with 65.0% having values consistent with iodine deficiency (< 50 microg/g). When results were expressed as micrograms per deciliter, the percentage having values consistent with iodine deficiency (< 5.0 microg/dl) increased to 95.7%. The findings suggest a primary role for iodine deficiency in goitrogenesis in the study population. They demonstrate that classification of the severity of the endemia in this or other study populations in areas of iodine deficiency is dependent on the methods used to determine goiter prevalence (palpation or ultrasound measured thyroid enlargement), or dietary iodine status (iodine excretion expressed as micrograms per gram creatinine or micrograms per deciliter urine). PMID:10524568

  1. 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

  2. Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

    PubMed Central

    Ma, Zheng Feei

    2014-01-01

    Background: Thyroglobulin, produced exclusively by the thyroid gland, has been proposed to be a more sensitive biomarker of iodine status than thyrotropin or the thyroid hormones triiodothyronine and thyroxine. However, evidence on the usefulness of thyroglobulin (Tg) to assess iodine status has not been extensively reviewed, particularly in pregnant women and adults. Summary: An electronic literature search was conducted using the Cochrane CENTRAL, Web of Science, PubMed, and Medline to locate relevant studies on Tg as a biomarker of iodine status. Since urinary iodine concentration (UIC) is the recommended method to assess iodine status in populations, only studies that clearly reported both Tg and UIC were included. For the purpose of this review, a median Tg <13 μg/L and a median UIC ≥100 μg/L (UIC ≥150 μg/L for pregnant women) were used to indicate adequate iodine status. We excluded studies conducted in subjects with either known thyroid disease or those with thyroglobulin antibodies. The search strategy and selection criteria yielded 34 articles of which nine were intervention studies. The majority of studies (six of eight) reported that iodine-deficient pregnant women had a median Tg ≥13 μg/L. However, large observational studies of pregnant women, including women with adequate and inadequate iodine status, as well as well-designed intervention trials that include both Tg and UIC, are needed. In adults, the results were equivocal because iodine-deficient adults were reported to have median Tg values of either <13 or ≥13 μg/L. Only studies in school-aged children showed that iodine-sufficient children typically had a median Tg <13 μg/L. Some of the inconsistent results may be partially explained by the use of different methodological assays and failure to assess assay accuracy using a certified reference material. Conclusions: These data suggest that Tg does hold promise as a biomarker of iodine deficiency. However, it is associated

  3. 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

  4. Genetic alterations of differentiated thyroid carcinoma in iodine-rich and iodine-deficient countries.

    PubMed

    Vuong, Huy Gia; Kondo, Tetsuo; Oishi, Naoki; Nakazawa, Tadao; Mochizuki, Kunio; Inoue, Tomohiro; Tahara, Ippei; Kasai, Kazunari; Hirokawa, Mitsuyoshi; Tran, Thong Minh; Katoh, Ryohei

    2016-08-01

    BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine-rich country (Japan) and an iodine-deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele-specific polymerase chain reaction (AS-PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS, HRAS, and KRAS), and RT-PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E, RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine-rich and iodine-deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer. PMID:27264674

  5. 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…

  6. Treatment with Iodine in Pregnant Rats with Marginal Iodine Deficiency Improves Cell Migration in the Developing Brain of the Progeny.

    PubMed

    Zhang, Le; Zhai, Xiaodan; Liu, Yuhui; Li, Jing; Shan, Zhongyan; Teng, Weiping

    2016-05-01

    Marginal iodine deficiency is a common health problem in pregnant women. Epidemiological and animal studies had shown that marginally maternal iodine deficiency could cause the mild changes of maternal thyroid function, eventually lead to a negative effect on neurodevelopment. But the underlying mechanisms responsible for the neurological impairment remain unclear. The aim of this study is to explore whether marginally maternal iodine deficiency could produce subtle changes in cell migration and cognitive function of offspring, and the optimal time of giving intervention to minimize the adverse effects. In the present study, we established a marginal iodine deficiency model, and iodine supplement was performed on pre-pregnancy (PP), G13 (gestation day 13), and postnatal day 0 (P0). Our data showed that there were changes in the cytoarchitecture and the percentage of bromodeoxyuridine (BrdU)-labeled cells in the cerebral cortex in marginal iodine deficiency rats. The Reelin expression was significantly lower, but Tenascin-C was higher in the cerebral cortex of marginal iodine deficiency group on P7 than the normal group, respectively. When iodine supplement, especially before G13 could reverse the abnormal expression of the two proteins involved in cell migration, which was consistent with the results of Morris Water Maze test. The three intervention groups had shorter escape latencies than the marginal iodine deficiency rats. The earlier that iodine is supplied, the better behavior performance would reach. Our findings suggested that iodine supplement in early stage of pregnancy could improve the cell migration of cerebral cortex and neurodevelopment of offspring. PMID:25963726

  7. Iodine deficiency among Belgian pregnant women not fully corrected by iodine-containing multivitamins: a national cross-sectional survey.

    PubMed

    Vandevijvere, Stefanie; Amsalkhir, Sihame; Mourri, Ahmed Bensouda; Van Oyen, Herman; Moreno-Reyes, Rodrigo

    2013-06-28

    Low iodine intake during pregnancy may cause thyroid dysfunction in pregnant women and their newborn. In the present study, iodine status among a nation-wide representative sample of Belgian pregnant women in the first and third trimester of pregnancy was determined, and determinants of iodine status were assessed 1 year after the introduction of bread fortified with iodised salt. The women were selected according to a multistage proportionate-to-size sampling design. Urine samples were collected and a general questionnaire was completed face to face with the study nurse. The median urinary iodine concentration (UIC) among pregnant women (n 1311) was 124.1mg/l and 122.6 mg/g creatinine when corrected for urinary creatinine. The median UIC in the first trimester (118.3 mg/l) was significantly lower than that in the third trimester (131.0 mg/l) but significantly higher than among non-pregnant women (84.8 mg/l). Iodine-containing supplement intake was reported by 60.8% of the women and 57.4% of the women took this supplement daily. The risk of iodine deficiency was significantly higher in younger women, in women not taking iodine-containing supplements, with low consumption of milk and dairy drinks and during autumn. Women with a higher BMI had a higher risk of iodine deficiency but the risk was lower in women who reported alcohol consumption. The median UIC during pregnancy indicates iodine deficiency in Belgium and some women are at a higher risk of deficiency. The current low iodine intake in women of childbearing age precludes the correction of iodine deficiency in pregnant women supplemented with multivitamins containing 150 mg iodine as recommended. PMID:23084115

  8. 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. PMID:20172468

  9. 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

  10. [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

  11. 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

  12. Work of the Polish Council for Control of Iodine Deficiency Disorders, and the model of iodine prophylaxis in Poland.

    PubMed

    Szybiński, Zbigniew

    2012-01-01

    The Polish Council for Control of Iodine Deficiency Disorders (PCCIDD) was established in 1991 in Krakow at the Chair and Dept. of Endocrinology, Jagiellonian University, Collegium Medicum, following the example of the International Council for Control of Iodine Deficiency Disorders (ICCIDD) in Charlottesville, USA. The PCCIDD co-operates with the European Co-ordinating Centre in Pisa, Italy. The PCCIDD comprises a group of experts in endocrinology, iodine prophylaxis, the technology of salt and food iodisation, and Polish representatives of several organisations: WHO, UNICEF, the Polish Consumers Federation, and the Spokesman for Children's Rights. The strategic goal of the Polish Council is to solve the problem of iodine deficiency in Poland realising the Programme for Elimination of Iodine Deficiency financed by the Ministry of Health. The Polish model of iodine prophylaxis contains obligatory iodisation of household salt (20-40 mg KI/1 kg) and neonates' formula (10 μg/100 mL of milk), and additional supplementation for pregnant and breastfeeding women with 150-200 μg of iodine as pharmacotherapy. The model is very effective: endemic goitre in schoolchildren has been eradicated, the prevalence of goitre in pregnant women has fallen from 80% to 19%, the frequency of transient hypothyroidism in neonates has dropped from 2.0% to 0.16%, and the observed increase of incidence rate of thyroid cancer in women over 40 years old has diminished markedly. In 2008, a WHO Collaborating Centre (WHOCC) for Nutrition was designated at the Department of Endocrinology, UJCM in Krakow. The main goal of the WHOCC is to sustain effective iodine prophylaxis in Poland in the light of the latest WHO recommendations on the necessary reduction of daily salt intake as a risk factor for hypertension and arteriosclerosis. Therefore, additional standardised carriers of iodine (milk, mineral water) have been introduced into the food market. PMID:22538756

  13. [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

  14. In Vivo Evaluation of Transdermal Iodide Microemulsion for Treating Iodine Deficiency Using Sprague Dawley Rats.

    PubMed

    Alayoubi, Alaadin; Sullivan, Ryan D; Lou, Hao; Patel, Hemlata; Mandrell, Timothy; Helms, Richard; Almoazen, Hassan

    2016-06-01

    The objective of this study was to evaluate the transdermal efficiency of iodide microemulsion in treating iodine deficiency using rats as an animal model. Animals were fed either iodine-deficient diet (20 μg/kg iodide) or control diet (200 μg/kg iodide) over a 17-month period. At month 14, iodide microemulsion was applied topically in iodine-deficient group and physiological evaluations of thyroid gland functions were characterized by monitoring the thyroid hormones (T3, T4), thyroid-stimulating hormone (TSH), iodide ion excretion in urine, and the overall rat body weights in both groups. Moreover, morphological evaluations of thyroid gland before and after treatment were performed by ultrasound imaging and through histological assessment. Prior to microemulsion treatment, the levels of T3, T4, and TSH in iodine-deficient group were statistically significant as compared to that in the control group. The levels of T3 and T4 increased while TSH level decreased significantly in iodine-deficient group within the first 4 weeks of treatment. After treatment, iodide concentration in urine increased significantly. There was no statistical difference in weight between the two groups. Ultrasound imaging and histological evaluations showed evidence of hyperplasia in iodine-deficient group. Topical iodide microemulsion has shown a promising potential as a novel delivery system to treat iodine deficiency. PMID:26288943

  15. 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. PMID:22987596

  16. The new emergence of iodine deficiency in the UK: consequences for child neurodevelopment.

    PubMed

    Rayman, Margaret P; Bath, Sarah C

    2015-11-01

    Adequate iodine intake is important during pregnancy as it is a component of the thyroid hormones that are crucial for fetal brain and neurological development. While randomized controlled trials in severe iodine deficiency have shown that iodine deficiency in pregnancy causes impaired offspring cognition, less is known of the effects in regions of mild/mild-to-moderate deficiency. The United Kingdom is now classified as mildly iodine deficient by the World Health Organization, based on a 2011 national study of 14-15-year-old schoolgirls. As pregnancy is the most critical time for brain development, we evaluated iodine status in pregnant women in Surrey (n = 100) and Oxford (n = 230). The median urinary iodine concentration was 85.3 μg/L in Surrey women, considerably lower than the WHO/United Nations Children's Fund/International Council for the Control of Iodine Deficiency Disorders cut-off of 150 μg/L. Oxford women had similarly low status. We investigated whether that level of iodine deficiency was associated with adverse child cognitive effects using stored samples and data from the Avon Longitudinal Study of Parents and Children cohort. In adjusted analyses, we found a significant association between low maternal iodine status in early pregnancy (urinary iodine-to-creatinine ratio <150 μg/g) such that children had an approximately 60% greater risk of being in the bottom quartile of scores for verbal intelligence quotient, reading accuracy and comprehension. UK women who might become pregnant should ensure they have adequate iodine status to avoid compromising their children's brain development. PMID:26240435

  17. 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

  18. 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

  19. 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

  20. 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. PMID:24398008

  1. A Review: Radiographic Iodinated Contrast Media-Induced Thyroid Dysfunction

    PubMed Central

    Leung, Angela M.; Braverman, Lewis E.; Brent, Gregory A.; Pearce, Elizabeth N.

    2015-01-01

    Context: Thyroid hormone production is dependent on adequate iodine intake. Excess iodine is generally well-tolerated, but thyroid dysfunction can occur in susceptible individuals after excess iodine exposure. Radiological iodinated contrast media represent an increasingly common source of excess iodine. Objective: This review will discuss the thyroidal response after acute exposure to excess iodine; contrast iodine-induced thyroid dysfunction; risks of iodine-induced thyroid dysfunction in vulnerable populations, such as the fetus, neonate, and patients with impaired renal function; and recommendations for the assessment and treatment of contrast iodine-induced thyroid dysfunction. Methods: Data for this review were identified by searching PubMed, Google Scholar, and references from relevant articles from 1948 to 2014. Conclusions: With the increase in the use of computed tomography scans in the United States, there is increasing risk of contrast-induced thyroid dysfunction. Patients at risk of developing iodine-induced thyroid dysfunction should be closely monitored after receiving iodinated contrast media and should be treated as needed. PMID:25375985

  2. 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

  3. 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.

  4. 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

  5. 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

  6. [Neonatal monitoring of congenital hypothyroidism in a mild iodine-deficiency region].

    PubMed

    Radzivil, T T; Krat, I V

    2006-07-01

    The paper analyzes the 2001-2004 data on congenital thyroid deficiency in a mild iodine-deficiency region. There is an increase in the number of neonatal infants with abnormally high thyroid-stimulating hormone (TSH) values. There is evidence that there is a need for neonatal TSH screening. The latter makes it possible to diagnose congenital thyroid deficiency from the first days of a baby's life and to prevent serious consequences in future. PMID:16925057

  7. 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...

  8. [Iodine-induced hyperthyroidism after cadexomer iodine treatment of leg ulcers].

    PubMed

    Michanek, A; Hansson, C; Berg, G; Månesköld-Claes, A

    1998-12-01

    The article consists in two case reports of eldery patients who developed hyperthyroidism after cadexomer iodine treatment of small leg ulcers. The first was an 87-year-old woman who developed anxiety, hoarseness and tachycardia after five months treatment of a 12 cm2 leg ulcer with 350 g cadexomer iodine. Her serum level of free thyroxine (FT4) was 23.1 pmol/l (normal range, 11.7-28.0), and that of thyroid-stimulating hormone (TSH) 0.01 mIU/l (normal range, 0.1-3.0). She had had a nodular goitre for thirty years. The second was an 86- year-old woman who developed depression and confusion after three months' treatment of an 8 cm2 leg ulcer with 170 g cadexomere iodine. Her serum level of FT4 was 30.0 pmol/l, and that of TSH 0.005 mIU/l. Both patients underwent Tc99m pertechnetate scanning and iodine uptake measurement with a view to treating the hyperthyroidism with radio-iodine. However, as iodine uptake was inhibited in both cases, radio-iodine treatment was impossible, and symptomatic treatment and antithyroid drugs had to be used. Thus, it is concluded that topical treatment with cadexomer iodine can induce hyperthyroidism difficult to manage clinically as the treatment options are limited, which should be borne in mind when cadexomer iodine treatment is considered. PMID:9889495

  9. [Assessment of the level of urinary iodine deficiency in children of Senegalese central regions].

    PubMed

    Sall, N D; Sall, M G; Sarr, N G; Gaye, O; Diatta, A; Diallo, F; Mbaye, A M; Ndiaye, B; Toure, M

    2000-01-01

    Iodine deficiency disorders (IDD) are a major public health problem in Senegal, where strategies of salt iodization were adopted in the southern and eastern regions. The aim of this study led in four districts (Koungheul, Bambey, Mekhe and Kebemer), was to estimate by a questionnaire, the women knowleges, attitudes and practices (KAP) concerning IDD, and to measure children urinary iodine excretion by the Sandell-Kolthoff method to assess a potential deficiency. Six hundred ninety eight households were selected covering 1336 women (age 15 to 49 years) and 400 children (age 6 to 12 years). Sixty three per cent of the women knew the goiter, 89% of them considered that it was a disease and only 0.6% knew the role of iodized salt in the treatment. On the other hand, 20% of the children presented a normal range of urinary iodine excretion superior to 100 microg/l, the deficiency was light (50 to 100 microg/l) in 38% of the children, moderate (25 to 50 microg/l) in 27% and severe (< 25 microg/l) in 15% of them. These results show that other Senegalese regions are concerned by iodine deficiency disorders and need information, education and iodine supplementation programmes, notably for children and young women. PMID:15779170

  10. 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.

  11. 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. PMID:27244854

  12. 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

  13. 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

  14. Iodine in diet

    MedlinePlus

    ... good sources are plants grown in iodine-rich soil. Side Effects Lack of enough iodine (deficiency) may occur in places that have iodine-poor soil. Many months of iodine deficiency in a person's ...

  15. Iodine

    MedlinePlus

    ... of iodine are POSSIBLY UNSAFE. Adults should avoid prolonged use of doses higher than 1100 mcg per ... enlarged thyroid gland (goiter), or a thyroid tumor: Prolonged use or high doses of iodine might make ...

  16. 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 ...

  17. 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.

  18. 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

  19. 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

  20. [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

  1. 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

  2. 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

  3. [Dietary iodine intake in children and clinical and biochemical features of iodine deficiency in chosen districts of south-east Poland].

    PubMed

    Tylek, D; Rybakowa, M; Sołtysik-Wilk, E; Ratajczak, R; Dłuzniewska, K; Zygmunt, A; Szczepaniak, B

    1992-01-01

    The study on the effects of Czarnobyl accident on thyroid gland function in children (MZ XVII program) revealed a high incidence of goiter in the population of children in district Kraków and Nowy Sacz. Other study on Tarnobrzeg population showed that the frequency of goiter in school children was 67%. The goiter prevalence, urine iodine excretion and iodine food consumption in the same populations were compared. The detailed investigation of iodine intake in children by feeding questionnaire shows a low consumption of iodine. The urine iodine excretion in the population of Kraków-district was low, but higher than in Nowy Sacz-district and nearly normal in Tarnobrzeg. High frequency of goiter in children and of IDD in newborns screened for CH, as well as low urine iodine excretion, together with low iodine intake with food are the markers of iodine deficiency in Kraków and Nowy Sacz districts. The improvement of feeding as well as iodine salt supplementation is necessary. The situation in Tarnobrzeg district looks differently and needs additional study. PMID:1345589

  4. Prevalence of thyroid dysfunction in elderly subjects from the general population in an iodine deficiency area.

    PubMed

    Hintze, G; Burghardt, U; Baumert, J; Windeler, J; Köbberling, J

    1991-12-01

    The prevalence of thyroid disorders was investigated in 466 (403 female, 63 male) subjects over the age of 60 years (79.2 +/- 7.5 years; mean +/- SD) from the general population in an area of iodine deficiency. In addition to thyroid hormone assays, thyroid antibodies and urinary iodine excretion were determined. In cases with thyroid dysfunction, ultrasound investigations were performed. Twenty-two of the 466 subjects (4.7%) showed hyper- or hypothyroidism; 7 subjects were hyperthyroid (1.5%), 5 had primary hypothyroidism (1.1%), and 10 showed "subclinical" hypothyroidism (2.2%). The latter constellation is defined as an elevation of thyrotropin (TSH) with normal values for thyroxine and triiodothyronine. Most subjects with hyperthyroidism had a goiter by palpation (6/7); thyroid volume by ultrasound (median) was 26.2 mL with an inhomogeneous echo pattern in 6 of the 7 subjects. In 4 cases, a rise in urinary iodine excretion was documented; none had TSH-receptor antibodies. Most subjects with overt or subclinical hypothyroidism had a homogeneous or low-echogenic pattern by ultrasound; thyroid volume (median) was 12.9 mL and 12.7 mL, respectively. By palpation, 8 of the 15 subjects had no goiter. In general, these persons had no rise in urinary iodine excretion (11/13), but most showed an elevation of antibodies against the microsomal antigen and/or thyroglobulin (11/15).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1841604

  5. 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

  6. Blocking type immunoglobulins in patients with nongoitrous primary hypothyroidism in area of iodine deficiency.

    PubMed

    Tang, T; Wang, Y G; Tsuboi, K; Irie, M; Ma, T; Ingbar, S H

    1991-12-01

    We have evaluated the role of circulating serum immunoglobulins (IgG) which inhibit the growth of thyroid in the etiology of thyroid atrophy in endemic cretinism. Twenty nongoitrous cretins (13 women and 7 men, age range: 9-33) were classified on the basis of clinical criteria for cretinism in China. They were born and living in an iodine deficient area, Xinjiang, northwest China. Antimicrosomal antibody titers were negative in all serum. Nine patients (seven women and two men; age range: 11-23) were biologically primary hypothyroid. Seven subjects were of a myxedematous form and two subjects were of a mixed form. We have studied thyroid-growth inhibiting immunoglobulin (TGII) activity that was measured as an inhibitory effect of 4 mg/ml IgG on TSH-induced [3H]-thymidine incorporation into the DNA of a rat thyroid follicular cell line, FRTL5 cells. Six (five women and one man) out of the nine patients with primary hypothyroidism (66.7 percent) had TGII. We also measured other growth-blocking IgG that inhibited [3H]-thymidine incorporation into DNA stimulated by insulin-like growth factor-I (IGF-I), a growth factor working through a cAMP-independent pathway. Five (three women and two men) out of nine patients (55.6 percent) with nongoitrous primary hypothyroidism had IGF-I-blocking IgG. These results indicate that TGII plays an important role in atrophy of the thyroid in spite of increased serum TSH concentrations, and IgG which inhibits thyroid growth stimulated by IGF-I also might play a role in thyroid atrophy in some endemic cretins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1823034

  7. 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

  8. Iodine induced SCC of Zr alloys at constant strain rate

    NASA Astrophysics Data System (ADS)

    Goryachev, S. B.; Gritsuk, A. R.; Prasolov, F. F.; Snegirev, M. G.; Shestak, V. E.; Novikov, V. V.; Bibilashvili, Yu. K.

    1992-12-01

    Stress corrosion cracking of Zr and its alloys Zry-4, Zry-2 and Zr-1% Nb has been studied in flowing iodine vapour at a constant strain rate. The tests were performed using flat samples of Zr and its alloy claddings as well as Zr coated Zr-1% Nb claddings. Zr-1% Nb is shown to be more resistant to SCC as compared to Zry-4 and Zry-2. No corrosion induced failure of Zr or Zr-coated Zr-1% Nb claddings has been actually observed. The influence of strain rate, temperature and iodine partial pressure on SCC has been studied for Zr-1% Nb.

  9. 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...

  10. 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. PMID:26499787

  11. 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

  12. Iodine supplementation: benefits outweigh risks.

    PubMed

    Delange, F; Lecomte, P

    2000-02-01

    In 1990, iodine deficiency affected almost one-third of the world population and was the greatest single cause of preventable brain damage and mental retardation. Following a resolution adopted by the World Summit for Children in 1990. major programmes of iodine supplementation were implemented by the governments of the affected countries with the support of major donors. Iodisation of salt was recognised as the method of choice. Nine years later, by April 1999, 75% of the affected countries had legislation on salt iodisation and 68% of the affected populations had access to iodised salt. The prevalence of iodine deficiency disorders decreased drastically in most countries and the deficiency disappeared completely in some such as Peru. This result constitutes a public heath success unprecedented with a non-infectious disease. However, occasional adverse effects occurred. The principle effect is iodine-induced hyperthyroidism which occurs essentially in older people with autonomous nodular goitres, especially following iodine intake that is too rapid and of too massive an increment. The incidence of the disorder is usually low and reverts spontaneously to the background rate of hyperthyroidism or even below this rate after 1 to 10 years of iodine supplementation. The possible occurrence of iodine-induced thyroiditis in susceptible individuals has not been clearly demonstrated by large epidemiological surveys. Iodine supplementation is followed by an increased prevalence of occult papillary carcinoma of the thyroid discovered at autopsy but the prognosis of thyroid cancer is improved due to a shift towards differentiated forms of thyroid cancer that are diagnosed at earlier stages. Iodine-induced hyperthyroidism and other adverse effects can be almost entirely avoided by adequate and sustained quality control and monitoring of iodine supplementation which should also confirm adequate iodine intake. Available evidence clearly confirms that the benefits of correcting

  13. 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

  14. Treatment of Hypothyroidism due to Iodine Deficiency Using Daily Powdered Kelp in Patients Receiving Long-term Total Enteral Nutrition

    PubMed Central

    Takeuchi, Takako; Kamasaki, Hotaka; Hotsubo, Tomoyuki; Tsutsumi, Hiroyuki

    2011-01-01

    We investigated thyroid function and urinary iodine concentration (UIC) in seven patients with severe motor intellectual disabilities. All seven received total enteral nutrition (TEN) for more than three years with a daily iodine intake of less than 20 µg. They were diagnosed as hypothyroidism due to iodine deficiency (HID) because of high TSH levels (7.6–82.3 µIU/ml), lower free T4 (FT4 0.4–1.5 ng/dl), negative anti-thyroid antibodies (anti-thyroglobulin antibody, anti-thyroidal peroxidase antibody) and extremely low UIC (<25–58 µg/l) levels. We gave them 1–2 g powdered kelp (200–400 µg as iodine) once a day, which restored their thyroid function and normalized their UICs. We proposed that daily powdered kelp would be effective and safe to treat HID in patient receiving long term TEN. PMID:23926395

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

    PubMed Central

    Stewart, J C; Vidor, G I

    1976-01-01

    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. PMID:946162

  16. 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

  17. Laser-induced iodine desorption from impregnated polystyrene

    NASA Astrophysics Data System (ADS)

    Torres-Filho, A.; Leite, N. F.; Miranda, L. C. M.; Stempniak, R. A.

    1989-07-01

    The Ar+ laser-stimulated desorption of iodine molecules from an impregnated polystyrene film was investigated. The photoprocess induces a color change (from red to the transparent) and leaves in the film a marked print, which is related to the laser beam characteristics. The experimental data was fitted using a set of differential equations relating the time dependence of the film temperature and absorption coefficient. At low-power levels (<25 mW), the time evolution of the laser transmitted power could be well matched to the experimental data. The wavelength dependence of the marking process was also studied and the relative contribution of photodissociative and photothermal processes was inferred.

  18. Serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels in severe iodine deficiency.

    PubMed

    Alikaşifoğlu, Ayfer; Ozön, Alev; Yordam, Nurşen

    2002-01-01

    Iodine deficiency is an important public health problem worldwide. It is well known that it has severe consequences such as brain damage, developmental delay, deficits in hearing and learning and lower intellectual attainment. It also has a negative impact on growth. In this study, we aimed to address this issue and we assessed height standard deviation scores of children living in an area of severe iodine deficiency in comparison to those living in a mild iodine deficiency area. Serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also analyzed to investigate the mechanisms by which iodine depletion leads to growth failure. Pubertal children in a severe iodine deficient SID area had lower height standard deviation scores (HSDS), IGF-I and IGFBP-3 levels than those living in mild iodine deficient MID area. Similar findings could not be elucidated in the prepubertal age group. The major determinants of HSDS were age, IGF-I, IGFBP-3 and TSH. IGF-I and IGFBP-3 were negatively correlated with T4. These findings suggest that iodine deficiency has a negative impact on growth, as well as IGF-I and IGFBP-3 levels. This effect seems to be due to the derangements in thyroid hormone economy arising from iodine depletion. The degree of this impact may be related to the duration of iodine depletion or may be dependent on the developmental stage of the organism at the time of iodine depletion. PMID:12405432

  19. 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.

  20. Contrast-induced acute kidney injury following iodine opacification other than by intravascular injection

    PubMed Central

    Perrin, Tilman; Hemett, Ould Maouloud; Menth, Markus; Descombes, Eric

    2012-01-01

    Contrast-induced acute kidney injury (CI-AKI) classically occurs following the intravascular administration of iodinated contrast medium (CM). However, some cases of iodine-induced nephrotoxicity have been reported in patients who did not receive intravascular CM, as a consequence of iodine absorption through mucosae, burned skin or interstitial tissues. Recently, we observed the first case of CI-AKI occurring after an enteroclysis without any direct intravascular injection of CM. Here, we report this case, and review other clinical situations in which renal toxicity has been reported following the non-intravascular use of iodinated compounds. PMID:24175084

  1. Current prevalence of goiter determined by ultrasonography and associated risk factors in a formerly iodine-deficient area of Turkey.

    PubMed

    Kocak, Mustafa; Erem, Cihangir; Deger, Orhan; Topbas, Murat; Ersoz, Halil Onder; Can, Emine

    2014-09-01

    The aim of this study was to determine the prevalence of goiter and related risk factors in an adult population in a formerly iodine-deficient area of Turkey. In this cross-sectional study, we enrolled 2,500 subjects (1,270 women and 1,230 men, aged over 20 years) by multistage sampling. Blood and urine specimens were collected for the assessment of thyroid function. Thyroid ultrasonography (USG) was performed to measure thyroid volume and evaluate nodules. The overall goiter prevalence was 26.5 % (28.4 % in women, 24.5 % in men, P < 0.05). Median thyroid volume was 15.59 mL (13.65 mL in women, 17.96 mL in men, P < 0.0001). Median urinary iodine was 122.79 μg/L. USG revealed thyroid nodules in 35.2 % of the subjects (38.4 % in women, 31.8 % in men, P < 0.005). Age group analysis revealed the lowest rate in the 20-29-year age group (12.5 %), which increased with age, reaching the highest level (38.4 %) in the 70+ years age group. The prevalence of goiter was negatively correlated with education level and positively correlated with body mass index (BMI) and positive family history. According to occupation, goiter prevalence was highest in farmers (35.3 %) and housewives (32.2 %). Despite a normal range of current urinary iodine excretion levels, prevalence of goiter in this adult population in a formerly iodine-deficient province of Turkey remained high, even about 10 years after salt iodine supplementation program introduction. In addition, the goiter prevalence was higher for female gender, advanced age, positive family history of goiter, low education level, and high BMI. PMID:24415172

  2. Iodine Deficiency in a Parenteral Nutrition-Dependent Adolescent With Intestinal Pseudo-Obstruction.

    PubMed

    Mortensen, Melissa; Williamson, Nila; Davis, Cheryl; Kanyu Hsu, Evelyn; Javid, Patrick J; Horslen, Simon

    2016-07-01

    Routine supplementation of iodine in parenteral nutrition (PN) solutions is not current practice in the United States. In this case study, we describe an incidental finding of goiter in a long-term PN-dependent adolescent. With increased iodine screening, we then identified additional patients with undetectable urinary iodine concentrations in our population of children with short bowel receiving long-term PN. We hypothesize that 2 practice changes are possibly reducing iodine provision to long-term PN-dependent patients: transition to alcohol-based skin preparations and lipid minimization. PMID:25261415

  3. 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.

  4. 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

  5. [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

  6. 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

  7. 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

  8. Indicators to monitor progress of National Iodine Deficiency Disorders Control Programme (NIDDCP) and some observations on iodised salt in west Bengal.

    PubMed

    Kumar, S

    1995-01-01

    Iodine Deficiency Disorders (IDD) are widely prevalent in our country and their consequences for human development are well known. The scope of National Goitre Control Programme (NGCP) launched in 1962 was expanded and the programme was renamed as National Iodine Deficiency Disorders Control Programme (NIDDCP) to connote wider implications of iodine deficiency in population. It is necessary to monitor the progress of NIDDCP using quantifiable indicators to ensure achievement of programme objectives. Prevalence of iodine deficiency disorders, status of iodised salt and level of knowledge. Attitude & practice (KAP) of community regarding IDD and iodised salt are a few such indicators. Children in the age group of 8-10 years are considered most appropriate target group to monitor IDD prevalence. The quality of iodised salt assessed at various levels in West Bengal (using field testing kit) indicated 'satisfactory' iodine content (i.e. > or = 15 ppm) at wholesalers (84.3 per cent), retailers (74.3 per cent) and consumers (71.2 per cent) level. It is suggested that the quality of iodised salt should be periodically assessed and intensive educational campaigns on IDD be launched to create increased demand for consumption of iodised salt in the community. PMID:8690501

  9. 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

  10. Influence of iodine supplementation on serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels in severe iodine deficiency.

    PubMed

    Ozön, Alev; Alikaşifoğlu, Ayfer; Yordam, Nurşen

    2004-01-01

    Iodine deficiency is an important public health problem worldwide. In addition to severe consequences such as brain damage, developmental delay, deficits in hearing and learning, it also has a negative impact on growth. The negative impact of severe iodine deficiency (SID) on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) was shown previously. In this study we aimed to analyze the impact of iodine supplementation on growth and growth factors of children with SID. One hundred and four children (63 boys and 41 girls) aged 5-15 years participated in the study. Height standard deviation scores (HSDS), and serum levels of IGF-I and IGFBP-3 were assessed both before and six months after a single dose of iodized oil. Serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were also analysed to investigate the mechanisms by which alterations of iodine status may influence growth. Pubertal children had lower HSDS six months after iodine supplementation, while that of prepubertal children remained unchanged. IGF-I and IGFBP-3 levels decreased significantly and FT4 levels were suppressed six months after the supplementation, while TSH was normalized. These findings suggest a negative impact of iodine supplementation on growth factors in the short-term, which may be a direct effect of iodine repletion or an indirect effect caused by alterations in thyroid function. It may also be related to the method of supplementation used. Further studies are necessary to resolve these issues, as well as to examine the impact of iodine supplementation on growth in the long-term. PMID:15641262

  11. 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 ...

  12. 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...

  13. Povidone-iodine-induced burn: case report and review of the literature.

    PubMed

    Lowe, Donna O; Knowles, Sandra R; Weber, Elizabeth A; Railton, Craig J; Shear, Neil H

    2006-11-01

    Burns are a rare but potentially serious complication of povidone-iodine use. This rare adverse drug reaction developed in a 38-year-old woman who underwent laparoscopic right ovarian cystectomy and endometrial ablation as a day procedure involving application of the topical antiseptic 10% povidone-iodine solution. Two days later, the patient was admitted to the hospital with burning, pain, itching, marked redness, and blistering extending from her midback to buttocks. A stain on her back also was evident. Partial-thickness chemical burn was diagnosed. Review of the literature yielded 13 other cases of povidone-iodine-induced burn. This underrecognized adverse effect of povidone-iodine application typically occurs when the povidone-iodine has not been allowed to dry or has been trapped under the body of a patient in a pooled dependent position. The burn is usually seen immediately after the procedure or on the next day, and typically heals with minimum scarring within 3-4 weeks with conservative treatment. The commonly postulated mechanism is a chemical burn due to irritation coupled with maceration, friction, and pressure. Given the widespread use of povidone-iodine and the potential for development of infection after a burn, clinicians need to be aware of this possible povidone-iodine-associated adverse drug reaction, and of preventive measures. PMID:17064209

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

    2016-07-01

    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. PMID:26446907

  20. Chernobyl and iodine deficiency in the Russian Federation: an environmental disaster leading to a public health opportunity.

    PubMed

    Jackson, Richard J; DeLozier, David M; Gerasimov, Gregory; Borisova, Olga; Garbe, Paul L; Goultchenko, Lioudmila; Shakarishvili, George; Hollowell, Joseph G; Miller, Dayton T

    2002-01-01

    The Chernobyl nuclear disaster of April 26, 1986, triggered a chain of devastating events that later included an unexpected increase in childhood thyroid cancer and evidence of iodine deficiency (ID) in Russia. For the Russian people the Chernobyl event had profound psychological impacts, provoking anxiety about nuclear technology and mistrust of governmental control efforts. Frequently in public health a crisis is required to create the political will to manage longstanding problems, and public health officials must rapidly mobilize to take advantage of the opportunity. In this case, ID, previously not seen as a problem in Russia, was recognized to be potentially serious, and the Russian Federation, assisted by the catalytic bi-national effort of the U.S.-Russian Joint Commission on Economic and Technological Cooperation (Gore-Chernomyrdin Commission (GCC)) established a model salt iodization policy, developed a planning process, and implemented a program to prevent ID through a systematic approach that included the people, government, and private groups using open communication, dissemination of the findings, and action plans. By 1999, political will had been mobilized and over 20% of the nation's salt was being iodized, up from about 1% in 1996. Universal iodization of salt was not a specific objective of the GCC; however, the increasing availability of iodized salt is leading to the elimination of ID, which is now a political goal in Russia. The full realization of this goal will require more time for education, marketing, and possibly legislative action. PMID:12532684

  1. Impaired intrathyroidal iodine organification and iodine-induced hypothyroidism in euthyroid women with a previous episode of postpartum thyroiditis.

    PubMed

    Roti, E; Minelli, R; Gardini, E; Bianconi, L; Neri, T; Gavaruzzi, G; Ugolotti, G; Salvo, D; Braverman, L E

    1991-11-01

    Postpartum thyroiditis (PPT) is common and occurs in 1.7 to 16.7% of pregnant women, depending upon the study population. Most of these women develop transient hypothyroidism and thyroid function usually returns to normal. We have studied 11 euthyroid women with a previous history of PPT to determine the incidence of subtle defects in thyroid function measured by iodide-perchlorate (I-ClO4) discharge tests and TRH tests and to determine whether these women would develop iodide-induced hypothyroidism. Seven (64%) had positive I-ClO4 discharge tests and 5 (46%) had an abnormally high TSH response to TRH. Thyroid antimicrosomal and antithyroid peroxidase were positive in 8 women (73%) with a previous episode of PPT. The administration of pharmacological amounts of iodide (10 drops of saturated solution of potassium iodide daily) for 90 days to these 11 women resulted in elevated basal and TRH stimulated serum TSH concentrations in 8 (72.7%) compared to TSH values during iodide administration to women who had never been pregnant. Antimicrosomal and antithyroid peroxidase concentrations did not change during iodide administration. These findings strongly suggest that euthyroid women with a previous episode of PPT have permanent subtle defects in thyroid hormone synthesis and are inordinately prone to develop iodide-induced hypothyroidism, similar to findings previously reported in euthyroid subjects with Hashimoto's thyroiditis, with a previous episode of painful subacute thyroiditis, or previously treated with radioactive iodine or surgery for Graves' disease. PMID:1658032

  2. [Adaptation of thyroid function to excess iodine].

    PubMed

    Aurengo, Andre; Leenhardt, Laurence; Aurengo, Helyett

    2002-10-26

    NORMALLY: The production of thyroid hormones is normally stable, despite iodine supplies that may vary widely and even on sudden excess iodine. The metabolism of iodine is characterised by adapted thyroid uptake, the requirements varying on the age and physiological status of the individual (pregnancy, breastfeeding) and by insufficient supplies in several areas in France. IN THE CASE OF EXCESS: The mechanisms that permit the thyroid to adapt to a sudden or chronic excess of iodine are immature in the newborn and sometimes deficient in adults, and may lead to iodine-induced dysthyroidism. Thanks to the recent progress made in thyroid physiology, these mechanisms are now better known. PATHOLOGICAL IMPACT: Iodine-induced hyperthyroidisms in a healthy or pathological thyroid are frequent. They are predominantly related to amiodarone. Iodine-related hypothyroidism frequently appears in cases of pre-existing thyroid diseases (asymptomatic autoimmune thyroiditis, for example). They are frequent in the newborn, notably in the premature. The iodine prophylaxis organised in Poland following the Tchernobyl accident led to very few pathological consequences in adults or children. PMID:12448332

  3. 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

  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. Comparative studies of UV-induced DNA cleavage by structural isomers of an iodinated DNA ligand

    SciTech Connect

    Martin, R.F.; Green, A.; Denison, L.; Pardee, M.; Kelly, D.P.; Roberts, M.; Rose, M.; Reum, M.

    1994-06-15

    The purpose was to evaluate the importance of the position of the halogen atom in iodinated DNA-binding bibenzimidazoles, with respect to sensitization of UV-A-induced DNA breakage. Three analogues of iodoHoechst 33258, denoted ortho-, meta- and paraiodoHoechst, according to the site of iodine substitution, were synthesized. Plasmid DNA (pBR322) was used to assay UV-A-induced DNA single-strand breaks (ssbs). The location of the sites of strand breakage was determined by DNA sequencing gel analysis, using a [sup 32]P-endlabelled oligoDNA with a single binding site for the ligands. A clear trend in decreasing activity of sensitization of UV-induced DNA ssbs was established: Ortho- > meta-, para- > iodoHoechst 33258. The sequencing gel studies showed that orthoiodoHoechst was distinct from the other three compounds, with respect to the sites of DNA strand breakage and the chemistry of the cleavage reaction. The position of iodine substitution in iodinated bibenzimidazoles determines the location of the carbon-centered radical on the ligand in the minor groove of DNA. DNA strand cleavage is mediated by abstraction of a nearby deoxyribosyl H-atom. Hence, the position of the radical species determines: which deoxyribosyl group is attacked (i.e., site of cleavage relative to the ligand binding site); which H-atom is abstracted, more specifically which of the five deoxyribosyl carbons is involved (i.e., the chemistry of the cleavage reaction), and the stereochemistry of the transition state for the H-atom abstraction (and hence the efficiency or extent of strand breakage). The ortho-compound represents the best example to date of iodinated DNA ligands designed as potential radiation sensitizers, as an extension of the well-established sensitization by halogenated DNA precursors. 30 refs., 3 figs.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.

    PubMed

    Moriya, Shuichi; Izu, Yayoi; Arayal, Smriti; Kawasaki, Makiri; Hata, Koki; Pawaputanon Na Mahasarakhahm, Chantida; Izumi, Yuichi; Saftig, Paul; Kaneko, Kazuo; Noda, Masaki; Ezura, Yoichi

    2016-05-01

    Unloading induces bone loss and causes disuse osteoporosis. However, the mechanism underlying disuse osteoporosis is still incompletely understood. Here, we examined the effects of cathepsin K (CatK) deficiency on disuse osteoporosis induced by using sciatic neurectomy (Nx) model. After 4 weeks of surgery, CatK KO and WT mice were sacrificed and subjected to analyses. For cancellous bone rich region, Nx reduced the bone mineral density (BMD) compared to the BMD in the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in cancellous bone. Nx also reduced BMD in the mid shaft cortical bone compared to the BMD in the corresponding region on the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in the mid shaft cortical bone. Bone volume (BV/TV) was reduced by Nx in WT mice. In contrast, Cat-K deficiency suppressed such reduction in bone volume. Interestingly, CatK deficiency suppressed osteoclast number and osteoclast surface in the Nx side compared to sham side. When bone marrow cells obtained from Nx side femur of CatK-KO mice were cultured, the levels of the calcified area in culture were increased. Further examination of gene expression indicated that Nx suppressed the expression of genes encoding osteoblast-phenotype-related molecules such as Runx2 and alkaline phosphatase in WT mice. In contrast, CatK deficiency suppressed such reduction. These data indicate that CatK is involved in the disuse-induced bone mass reduction. PMID:26460818

  11. Role of iodine in diiodomethyl-p-tolylsulfone induced reproductive toxicity in rats: proposed mode of action.

    PubMed

    Saghir, Shakil A; Yano, Barry L; Zablotny, Carol L; Carney, Edward W

    2012-04-01

    The biocide diiodomethyl-p-tolylsulfone (DIMPTS) caused dystocia, decreased neonatal survival and hypothyroidism in rat reproduction studies resembling the effects caused by iodine. One molecule of DIMPTS contains two iodine moieties that are hydrolyzed upon ingestion and systemically absorbed, suggesting iodine toxicity as a probable mode of action for the effects observed in rats. This study compared the effects induced by DIMPTS and an equimolar concentration of its de-iodinated analogue, methyl-p-tolylsulfone (MPTS). Groups of 20 female Sprague Dawley rats were fed diets supplying 80 mg DIMPTS/kg/day, 32 mg MPTS/kg/day or control feed from prior to breeding through lactation and gonadal function, mating performance, conception, gestation, parturition, lactation, survival, growth and development of pups evaluated through postnatal day 7. Serum thyroid hormones and iodine levels in milk and sera were also determined. Females given DIMPTS had increased incidence of vulvar discharge and dystocia, decreased litter size, decreased body weights and feed consumption, increased thyroid weights, thyroid follicular cell hypertrophy with decreased colloid, decreased triidothyronine, and increased thyroid stimulating hormone levels. DIMPTS pups had decreased neonatal survival and body weights. These effects were associated with elevated levels of iodine in milk and sera. In contrast, MPTS did not produce similar effects in adult females or their offspring. These data support the hypothesis that the dystocia, altered neonatal survival and hypothyroidism following repeated dietary administration of DIMPTS were due to excessive iodine released from DIMPTS during absorption and metabolism. PMID:22051157

  12. 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

  13. Different Degrees of Iodine Deficiency Inhibit Differentiation of Cerebellar Granular Cells in Rat Offspring, via BMP-Smad1/5/8 Signaling.

    PubMed

    Dong, Jing; Lei, Xibing; Wang, Yi; Wang, Yuan; Song, Heling; Li, Min; Min, Hui; Yu, Ye; Xi, Qi; Teng, Weiping; Chen, Jie

    2016-09-01

    Iodine deficiency (ID) during development results in dysfunction of the central nervous system (CNS) and affects psychomotor and motor function. It is worth noting that maternal mild and marginal ID tends to be the most common reason of preventable neurodevelopmental impairment, via a mechanism that has not been elucidated. Therefore, our aim was to study the effects of developmental mild and marginal ID on the differentiation of cerebellar granule cells (GCs) and investigate the activation of BMP-Smad1/5/8 signaling, which is crucial for the development and differentiation of cerebellum. Three developmental rat models were created by feeding dam rats with a diet deficient in iodine and deionized water supplemented with potassium iodide. Our results showed that different degrees of ID inhibited and delayed the differentiation of cerebellar GCs on postnatal day (PN) 7, PN14, and PN21. Moreover, mild and severe ID reduced the expression of BMP2 and p-Smad1/5/8, and increased the levels of Id2 on PN7, PN14, and PN21. However, marginal ID rarely altered expression of these proteins in the offspring. Our study supports the hypothesis that mild and severe ID during development inhibits the differentiation of cerebellar GCs, which may be ascribed to the down-regulation of BMP-Smad1/5/8 signaling and the overexpression of Id2. Furthermore, it was speculated that maternal marginal ID rarely affected the differentiation of cerebellar GCs in the offspring. PMID:26307610

  14. 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

  15. 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.

  16. An Iodine-Vapor-Induced Cyclization in a Crystalline Molecular Flask.

    PubMed

    Knichal, Jane V; Shepherd, Helena J; Wilson, Chick C; Raithby, Paul R; Gee, William J; Burrows, Andrew D

    2016-05-10

    A vapor-induced cyclization has been observed in the host environment of a crystalline molecular flask (CMF), within which 1,8-bis(2-phenylethynyl)naphthalene (bpen), a diarenynyl system primed for cyclization, was exposed to iodine vapor to yield the corresponding indeno[2,1-α]phenalene species. The cyclization process, unique in its vapor-induced, solvent-free nature, was followed spectroscopically, and found to occur concurrently with the displacement of lattice solvent for molecular iodine in CMF⋅0.75 bpen⋅2.25 CHCl3 ⋅H2 O. The cyclization occurred under mild conditions and without the need to suspend the crystals in solvent. The ability of CMFs to host purely gas-induced reactions is further highlighted by the subsequent sequential oxidation reaction of cyclized 7-iodo-12-phenylindeno[2,1-α]phenalene (ipp) with molecular oxygen derived from air, yielding 12-hydroxy-7-iodo-2-phenylindeno[2,1-α]phenalen-1(12H)-one (hipp). PMID:27060377

  17. 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.

  18. Vitamin A Deficiency Induces Congenital Spinal Deformities in Rats

    PubMed Central

    Li, Zheng; Shen, Jianxiong; Wu, William Ka Kei; Wang, Xiaojuan; Liang, Jinqian; Qiu, Guixing; Liu, Jiaming

    2012-01-01

    Most cases of congenital spinal deformities were sporadic and without strong evidence of heritability. The etiology of congenital spinal deformities is still elusive and assumed to be multi-factorial. The current study seeks to elucidate the effect of maternal vitamin A deficiency and the production of congenital spinal deformities in the offsping. Thirty two female rats were randomized into two groups: control group, which was fed a normal diet; vitamin A deficient group, which were given vitamin A-deficient diet from at least 2 weeks before mating till delivery. Three random neonatal rats from each group were killed the next day of parturition. Female rats were fed an AIN-93G diet sufficient in vitamin A to feed the rest of neonates for two weeks until euthanasia. Serum levels of vitamin A were assessed in the adult and filial rats. Anteroposterior (AP) spine radiographs were obtained at week 2 after delivery to evaluate the presence of the skeletal abnormalities especially of spinal deformities. Liver and vertebral body expression of retinaldehyde dehydrogenase (RALDHs) and RARs mRNA was assessed by reverse transcription-real time PCR. VAD neonates displayed many skeletal malformations in the cervical, thoracic, the pelvic and sacral and limbs regions. The incidence of congenital scoliosis was 13.79% (8/58) in the filial rats of vitamin A deficiency group and 0% in the control group. Furthermore, vitamin A deficiency negatively regulate the liver and verterbral body mRNA levels of RALDH1, RALDH2, RALDH3, RAR-α, RAR-β and RAR-γ. Vitamin A deficiency in pregnancy may induce congenital spinal deformities in the postnatal rats. The decreases of RALDHs and RARs mRNA expression induced by vitamin A deprivation suggest that vertebral birth defects may be caused by a defect in RA signaling pathway during somitogenesis. PMID:23071590

  19. Chemical aspects of iodine-induced stress corrosion cracking failure of zircaloy-4 tubing above 50°C

    NASA Astrophysics Data System (ADS)

    Hofmann, P.; Spino, J.

    1983-02-01

    The chemical environment associated with iodine-induced SCC failure of Zircaloy-4 tubing above 500°C has been characterized. At the critical iodine concentrations which result in SCC initiation and propagation, most of the iodine is present as condensed zirconium subiodides ( I/ Zr ⩽ 0.4). Only a small part of the iodine remains in the gas phase as ZrI 4. The gaseous ZrI 4 is probably responsible for crack initiation and propagation. The critical ZrI 4 pressures for SCC failure have been estimated in zircaloy/iodine reaction experiments performed with unstressed zircaloy tube specimens. These pressures were confirmed in additional creep rupture tests conducted under controlled ZrI 4 partial pressure conditions. The estimated critical ZrI 4 pressure above which low-ductility SCC failure of the zircaloy tubing always occurs, independent of time-to-failure, varies between 0.005 bar at 550°C and 0.043 bar at 800°C. Below the critical values, however, a rather wide range of ZrI 4 pressures is associated with the onset of the SCC, especially at temperatures below 800°C. A comparison of the experimental results with available thermochemical data in the Zr-I system indicates that the main reaction involved during crack propagation is chemisorption of iodine-containing species on the fresh zircaloy surfaces created by metal straining at the crack tip.

  20. [Improving the human iodine supply by iodination of swine feed].

    PubMed

    Rambeck, W A; Kaufmann, S; Feng, J; Hollwich, W; Arnold, R

    1997-07-01

    Germany and several other countries are areas of severe iodine deficiency. In addition to iodized salt additional strategies to fight iodine deficiency exist. A promising possibility is the supplementation of feed with iodine, in order to increase its content in food of animal origin. In a feeding experiment 24 male castrated and female piglets of the cross breed Deutsche Landrasse x Pietrain were fed a high iodine supplemented diet. At a body weight of 100 kg the animals were slaughtered and the effect of the iodine supplementation on iodine content in the organs was studied. Animals receiving 30 mg iodine/kg feed showed significantly higher iodine contents in muscle, heart, kidney, liver, serum, fat and in the thyroidea than animals receiving no iodine supplementation. The iodine content in muscle and organs increased by a factor three to seven. Concerning meat quality and other slaughter parameters there was no difference between the two groups. This demonstrates that this strategy is in addition to iodized salt a possibility to reduce iodine deficiency. PMID:9312888

  1. Coherent pulse propagation and self-induced transparency on degenerate transitions in atomic iodine

    NASA Astrophysics Data System (ADS)

    Xu, Gan; King, T. A.

    1984-07-01

    Coherent propagation of intense short laser pulses through degenerate absorbing media is investigated with the use of an atomic-iodine laser-absorber self-resonant combination. Four degenerate systems, the 2P12-2P32, F=3<-->F'=4, ΔMF=0,+/-1 and F=2<-->F'=2, ΔMF=0,+/-1 transitions, are studied under various conditions. Theoretical analysis based on the "pulse-area-pulse-energy" approach shows different pulse propagation behaviors for three typical types of degeneracy. Experimental results give good agreement with theoretical predictions. It is concluded that self-induced transparency exists in any degenerate two-level system, provided that suitable polarization of radiation is used. The usefulness of self-induced-transparency phenomena for measurements of transitional dipole moment and homogeneous relaxation time is also demonstrated.

  2. Exercise-induced oxidative stress: glutathione supplementation and deficiency.

    PubMed

    Sen, C K; Atalay, M; Hänninen, O

    1994-11-01

    Glutathione (GSH) plays a central role in coordinating the synergism between different lipid- and aqueous-phase antioxidants. We documented 1) how exogenous GSH and N-acetylcysteine (NAC) may affect exhaustive exercise-induced changes in tissue GSH status, lipid peroxides [thiobarbituric acid-reactive substances (TBARS)], and endurance and 2) the relative role of endogenous GSH in the circumvention of exercise-induced oxidative stress by using GSH-deficient [L-buthionine-(S,R)-sulfoximine (BSO)-treated] rats. Intraperitoneal injection of GSH remarkably increased plasma GSH; exogenous GSH per se was an ineffective delivery agent of GSH to tissues. Repeated administration of GSH (1 time/day for 3 days) increased blood and kidney total GSH [TGSH; GSH+oxidized GSH (GSSG)]. Neither GSH nor NAC influenced endurance to exhaustion. NAC decreased exercise-induced GSH oxidation in the lung and blood. BSO decreased TGSH pools in the liver, lung, blood, and plasma by approximately 50% and in skeletal muscle and heart by 80-90%. Compared with control, resting GSH-deficient rats had lower GSSG in the liver, red gastrocnemius muscle, heart, and blood; similar GSSG/TGSH ratios in the liver, heart, lung, blood, and plasma; higher GSSG/TGSH ratios in the skeletal muscle; and more TBARS in skeletal muscle, heart, and plasma. In contrast to control, exhaustive exercise of GSH-deficient rats did not decrease TGSH in the liver, muscle, or heart or increase TGSH of plasma; GSSG of muscle, blood, or plasma; or TBARS of plasma or muscle. GSH-deficient rats had approximately 50% reduced endurance, which suggests a critical role of endogenous GSH in the circumvention of exercise-induced oxidative stress and as a determinant of exercise performance. PMID:7868431

  3. 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.

  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. Iodine-induced thyrotoxic hypokalemic paralysis after ingestion of Salicornia herbace.

    PubMed

    Yun, Seong Eun; Kang, Yeojin; Bae, Eun Jin; Hwang, Kyungo; Jang, Ha Nee; Cho, Hyun Seop; Chang, Se-Ho; Park, Dong Jun

    2014-04-01

    A 56-year-old Korean man visited to emergency room due to paroxysmal flaccid paralysis in his lower extremities. There was no family or personal history of periodic paralysis. His initial potassium levels were 1.8 mmol/L. The patient had been taking Salicornia herbacea for the treatment of diabetes and hypertension. Results of a thyroid function test were as follows: T3 = 130.40 ng/dL, TSH = 0.06 mIU/L, and free T4 = 1.73 ng/dL. A thyroid scan exhibited a decreased uptake (0.6%). His symptoms clearly improved and serum potassium levels increased to 4.4 mmol/L by intravenous infusion of only 40 mmol of potassium chloride. Eight months after the discontinuation of only Salicornia herbacea, the patient's thyroid function tests were normalized. Large amounts of iodine can induce hypokalemic thyrotoxic paralysis and it may be necessary to inquire about the ingestion of iatrogenic iodine compounds, such as Salicornia herbacea. PMID:24344747

  6. Dysferlin deficiency confers increased susceptibility to coxsackievirus-induced cardiomyopathy.

    PubMed

    Wang, Chen; Wong, Jerry; Fung, Gabriel; Shi, Junyan; Deng, Haoyu; Zhang, Jingchun; Bernatchez, Pascal; Luo, Honglin

    2015-10-01

    Coxsackievirus infection can lead to viral myocarditis and its sequela, dilated cardiomyopathy, which represent major causes of cardiovascular mortality worldwide in children. Yet, the host genetic susceptible factors and the underlying mechanisms by which viral infection damages cardiac function remain to be fully resolved. Dysferlin is a transmembrane protein highly expressed in skeletal and cardiac muscles. In humans, mutations in the dysferlin gene can cause limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin deficiency has also been linked to cardiomyopathy. Defective muscle membrane repair has been suggested to be an important mechanism responsible for muscle degeneration in dysferlin-deficient patients and animals. Using both naturally occurring and genetically engineered dysferlin-deficient mice, we demonstrated that loss of dysferlin confers increased susceptibility to coxsackievirus infection and myocardial damage. More interestingly, we found that dysferlin is cleaved following coxsackieviral infection through the proteolytic activity of virally encoded proteinases, suggesting an important mechanism underlying virus-induced cardiac dysfunction. Our results in this study not only identify dysferlin deficiency as a novel host risk factor for viral myocarditis but also reveal a key mechanism by which coxsackievirus infection impairs cardiac function, leading to the development of dilated cardiomyopathy. PMID:26073173

  7. 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.

  8. 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

  9. 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. PMID:26549792

  10. 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

  11. 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

  12. P8 deficiency increases cellular ROS and induces HO-1.

    PubMed

    Weis, Sebastian; Bielow, Tobias; Sommerer, Ines; Iovanna, Juan; Malicet, Cédric; Mössner, Joachim; Hoffmeister, Albrecht

    2015-01-01

    The gene p8 encodes for a small cytoprotective protein with no apparent enzymatic activity being proposed to act as co-transcription factor whose expression is increased during inflammation. Recent data from astrocytes demonstrates that p8 suppression leads to induction of heme oxygenase 1 (HO-1). Here, we assessed the cross-talk between p8 and HO-1 in mouse embryonic fibroblasts (MEF) observing an increased expression of HO-1 in p8-deficient (p8(-/-)) MEFs in non-treated and treated conditions. This effect was independent of the cell cycle. Our findings revealed that generation of reactive oxygen species (ROS) was higher in p8(-/-) MEFs. Mitochondria and NADPH oxidases were not the origin of ROS. This observation was not restricted to MEF as suppression of p8 gene transcription in MiaPaCa-2 cells also led to increased intracellular ROS. Additionally, p8 deficiency did not affect the Rac1 dependant NADPH oxidase complex. Our data shows that p8 deficiency increases ROS and subsequently the expression of anti-oxidative enzymes, such as HO-1, suggesting an involvement in the anti-oxidative defense. Moreover, we suggest that the severity of AP observed in p8(-/-) mice is induced by an impaired anti oxidative capacity of the pancreas, which is caused by increased generation of ROS. PMID:25475530

  13. Zinc deficiency induces depression-like symptoms in adult rats.

    PubMed

    Tassabehji, Nadine M; Corniola, Rikki S; Alshingiti, Almamoun; Levenson, Cathy W

    2008-10-20

    There is mounting evidence suggesting a link between serum zinc levels and clinical depression. Not only is serum zinc negatively correlated with the severity of symptoms, but zinc levels appear to be lowest in patients who do not respond to antidepressant drug therapy. It is not known if reduced zinc levels are contributing to depression, or the result of dietary or other factors associated with major depression. Thus, we designed this study to test the hypothesis that dietary zinc deficiency would induce depression-like behaviors in rats. Two-month-old male rats were fed zinc adequate (ZA, 30 ppm), deficient (ZD, 1 ppm), or supplemented (ZS, 180 ppm) diets for 3 weeks. Consistent with the development of depression, ZD rats displayed anorexia (p<0.001), anhedonia (reduced saccharin:water intake, p< 0.001), and increased anxiety-like behaviors in a light-dark box test (p<0.05). Furthermore, the antidepressant drug fluoxetine (10 mg/kg body wt) reduced behavioral despair, as measured by the forced swim test, in rats fed the ZA and ZS rats (p<0.05), but was ineffective in ZD rats. Together these studies suggest that zinc deficiency leads to the development of depression-like behaviors that may be refractory to antidepressant treatment. PMID:18655800

  14. 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.

  15. Iodine poisoning

    MedlinePlus

    Iodine is a naturally occurring chemical. Small amounts are needed for good health. However, large doses can ... Children are especially sensitive to the effects of iodine. NOTE: Iodine is found in certain foods. However, ...

  16. Persistent Optically Induced Magnetism in Oxygen-Deficient Strontium Titanate

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    Strontium titanate (SrTiO3) is a foundational material in the emerging field of complex oxide electronics. While its electronic, optical, and lattice properties have been studied for decades, SrTiO3 has recently become a renewed focus of materials research owing to the discovery of magnetism and superconductivity at interfaces between SrTiO3 and other oxides. The formation and distribution of oxygen vacancies may play an essential but as-yet-incompletely understood role. Here we observe an optically induced and persistent magnetization in slightly oxygen-deficient bulk SrTiO3-δ crystals using magnetic circular dichroism spectroscopy and SQUID magnetometry. The optically induced magnetization appears below ~18 K, persists for hours below 10 K, and is tunable via the polarization and wavelength of sub-bandgap (400-500 nm) light. These effects, which only occur in oxygen-deficient samples, reveal a detailed interplay between defects, magnetism, and light in oxide materials. W. D. Rice et al. submitted. See article on arXiv.

  17. Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats.

    PubMed

    Al-Majed, Abdulhakeem A

    2007-03-01

    This study investigates whether or not carnitine deficiency is a risk factor and could contribute to cisplatin-induced liver toxicity. A total of 60 adult male Wistar albino rats were divided into six groups. The first three groups were injected intraperitoneally with normal saline, propionyl-l-carnitine (500 mg/kg), and d-carnitine (500 mg/kg), respectively, for 10 successive days. The fourth, fifth and sixth groups were injected intraperitoneally with the same doses of normal saline, propionyl-l-carnitine and d-carnitine, respectively, for 5 successive days before and after a single dose of cisplatin (7 mg/kg). Administration of the standard nephrotoxic dose of cisplatin did not produce any changes in serum alanine transaminase and gamma-glutamyl transferase and no morphological changes in liver tissues. However, it did produce a significant increase in thiobarbituric acid reactive substances and total nitrate/nitrite and a significant decrease in reduced glutathione content in liver tissues. On the other hand, combined treatment with cisplatin and d-carnitine induced a dramatic increase in serum alanine transaminase and gamma-glutamyl transferase, as well as progressive reduction in total carnitine and ATP content in liver tissue. Moreover, histopathological examination of liver tissues confirmed the biochemical data, where cisplatin and d-carnitine combination showed signs of liver injury manifested as focal necro-inflammatory changes and portal inflammation. Interestingly, in carnitine supplemented rats using propionyl-l-carnitine, cisplatin did not produce any biochemical and histopathological changes in liver tissues. In conclusion, data from this study suggest for the first time that (1) carnitine deficiency is a risk factor and could precipitate cisplatin-induced hepatotoxicity, (2) oxidative stress is not the main cause of cisplatin-related hepatotoxicity and (3) propionyl-l-carnitine prevents the development of cisplatin-induced liver injury. PMID

  18. Prevention and Management of Adverse Reactions Induced by Iodinated Contrast Media.

    PubMed

    Wu, Yi Wei; Leow, Kheng Song; Zhu, Yujin; Tan, Cher Heng

    2016-04-01

    Iodinated radiocontrast media (IRCM) is widely used in current clinical practice. Although IRCM is generally safe, serious adverse drug reactions (ADRs) may still occur. IRCM-induced ADRs may be subdivided into chemotoxic and hypersensitivity reactions. Several factors have been shown to be associated with an increased risk of ADRs, including previous contrast media reactions, history of asthma and allergic disease, etc. Contrast media with lower osmolality is generally recommended for at-risk patients to prevent ADRs. Current premedication prophylaxis in at-risk patients may reduce the risk of ADRs. However, there is still a lack of consensus on the prophylactic role of premedication. Contrast-induced nephropathy (CIN) is another component of IRCM-related ADRs. Hydration remains the mainstay of CIN prophylaxis in at-risk patients. Despite several preventive measures, ADRs may still occur. Treatment strategies for potential contrast reactions are also summarised in this article. This article summarises the pathophysiology, epidemiology and risk factors of ADRs with emphasis on prevention and treatment strategies. This will allow readers to understand the rationale behind appropriate patient preparation for diagnostic imaging involving IRCM. PMID:27292007

  19. 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

  20. 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

  1. 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

  2. Elimination of iodine deficiency disorders by 2000 and its bearing on the people in a district of Orissa, India: a knowledge-attitude-practices study.

    PubMed

    Mohapatra, S S; Bulliyya, G; Kerketta, A S; Geddam, J J; Acharya, A S

    2001-01-01

    A knowledge-attitude-practices (KAP) study was conducted along with a prevalence study of iodine deficiency disorders (IDD) between 1998-99 in the district of Bargarh, Orissa state, India. A total of 635 people were interviewed by a pretested structured questionnaire, adopting the probability proportional to size cluster sampling method. The aim was to assess the baseline information on the KAP of the people regarding IDD. Only 37% of the males and 29.3% of the females perceived goitre as a disease. Less than 5% of both sexes knew how goitre is caused. Only 16.4% used iodised salt regularly. The awareness and perception of IDD does not correspond with the time and effort we have spent in education of this disease. The implications of this poor knowledge about IDD and consequent poor use of iodised salt is contrasted to the optimistic target of elimination of IDD. This aspect is discussed in this paper, at a time when we are at the beginning of the new millennium. PMID:11708610

  3. 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.

  4. 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. PMID:25468924

  5. 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

  6. 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

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

    PubMed

    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

  8. 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

  9. 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.

  10. Dietary induced subclinical vitamin K deficiency in normal human subjects.

    PubMed Central

    Ferland, G; Sadowski, J A; O'Brien, M E

    1993-01-01

    A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K

  11. Iodine poisoning

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002658.htm Iodine poisoning To use the sharing features on this page, please enable JavaScript. Iodine is a naturally occurring chemical. Small amounts are ...

  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. PMID:20464381

  13. 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

  14. Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation

    PubMed Central

    Boehm, Olaf; El Aissati, Sakina; Foltz, Fabian; Goelz, Lina; Goertz, David; Kebir, Sied; Weisheit, Christina; Wolf, Michael; Meyer, Rainer; Baumgarten, Georg

    2015-01-01

    Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR)-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4-/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15mg/g bodyweight) or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization) signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4-/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4-/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced hyperinflammatory

  15. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity.

    PubMed

    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 (10mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4days 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. PMID:26148447

  16. 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. PMID:24607345

  17. Thiamine Deficiency Induces Anorexia by Inhibiting Hypothalamic AMPK

    PubMed Central

    Liu, Mei; Alimov, Alexander; Wang, Haiping; Frank, Jacqueline A.; Katz, Wendy; Xu, Mei; Ke, Zun-Ji; Luo, Jia

    2014-01-01

    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 16 days, 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 9 folds 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 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. PMID:24607345

  18. 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...

  19. 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.

  20. Auxin mediates patterning of cluster root development induced by phosphorus deficiency in Lupinus albus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White lupin (Lupinus albus L.) develops cluster roots under phosphorus (P) deficiency. This species is widely used as a model system to study the morphology and physiology of cluster roots. However, the mechanism of P deficiency-induced cluster root formation is not fully understood. To evaluate the...

  1. 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...

  2. 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...

  3. 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

  4. An innovative approach for iodine supplementation using iodine-rich phytogenic food.

    PubMed

    Weng, Huan-Xin; Liu, Hui-Ping; Li, De-Wang; Ye, Mingli; Pan, Lehua; Xia, Tian-Hong

    2014-08-01

    Iodine, as one of the essential trace elements for human body, is very important for the proper function of thyroid gland. In some regions, people are still suffering from iodine deficiency disorder (IDD). How to provide an effective and cost-efficient iodine supplementation has been a public health issue for many countries. In this review, a novel iodine supplementation approach is introduced. Different from traditional iodine salt supplement, this approach innovatively uses cultivated iodine-rich phytogenic food as the supplement. These foods are cultivated using alga-based organic iodine fertilizer. The feasibility, mechanics of iodine absorption of plants from soil and the bioavailability of iodine-rich phytogenic food are further discussed. PMID:24504625

  5. 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

  6. Vitamin D deficiency is a potential risk factor for contrast-induced nephropathy.

    PubMed

    Luchi, Weverton M; Shimizu, Maria Heloisa M; Canale, Daniele; Gois, Pedro Henrique F; de Bragança, Ana Carolina; Volpini, Rildo A; Girardi, Adriana C C; Seguro, Antonio C

    2015-08-01

    Vitamin D deficiency (VDD) is widespread in the general population. Iodinated (IC) or gadolinium-based contrast media (Gd) may decrease renal function in high-risk patients. This study tested the hypothesis that VDD is a predisposing factor for IC- or Gd-induced nephrotoxicity. To this end, male Wistar rats were fed standard (SD) or vitamin D-free diet for 30 days. IC (diatrizoate), Gd (gadoterate meglumine), or 0.9% saline was then administered intravenously and six groups were obtained as the following: SD plus 0.9% saline (Sham-SD), SD plus IC (SD+IC), SD plus Gd (SD+Gd), vitamin D-free diet for 30 days plus 0.9% saline (Sham-VDD30), vitamin D-free diet for 30 days plus IC (VDD30+IC), and vitamin D-free diet for 30 days plus Gd (VDD30+Gd). Renal hemodynamics, redox status, histological, and immunoblot analysis were evaluated 48 h after contrast media (CM) or vehicle infusion. VDD rats showed lower levels of total serum 25-hydroxyvitamin D [25(OH)D], similar plasma calcium and phosphorus concentration, and higher renal renin and angiotensinogen protein expression compared with rats fed SD. IC or Gd infusion did not affect inulin clearance-based estimated glomerular filtration rate (GFR) in rats fed SD but significantly decreased GFR in rats fed vitamin D-free diet. Both CM increased renal angiotensinogen, and the interaction between VDD and CM triggered lower renal endothelial nitric oxide synthase abundance and higher renal thiobarbituric acid reactive substances-to-glutathione ratio (an index of oxidative stress) on VDD30+IC and VDD30+Gd groups. Conversely, worsening of renal function was not accompanied by abnormalities on kidney structure. Additionally, rats on a VDD for 60 days displayed a greater fall in GFR after CM administration. Collectively, our findings suggest that VDD is a potential risk factor for IC- or Gd-induced nephrotoxicity most likely due to imbalance in intrarenal vasoactive substances and oxidative stress. PMID:26041113

  7. [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

  8. 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.

  9. Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

    PubMed Central

    Höller, Yvonne; Storti, Monica; Christova, Monica; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

    2013-01-01

    Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans. PMID:24235882

  10. Thiamine deficiency induced neurochemical, neuroanatomical, and neuropsychological alterations: a reappraisal.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Storti, Monica; Christova, Monica; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2013-01-01

    Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans. PMID:24235882

  11. Evaluation of the resistance of irradiated zirconium-liner cladding to iodine-induced stress corrosion cracking

    NASA Astrophysics Data System (ADS)

    Shimada, Sachio; Nagai, Masayuki

    1983-02-01

    An evaluation was made of irradiated zirconium-liner cladding for its resistance to iodine-induced stress corrosion cracking (SCC). Emphasis was put on irradiation-induced hardening in zirconium and SCC resistance in zirconium-liner cladding as compared with Zircaloy-2 cladding. The Vickers microhardness test revealed that crystal bar zirconium experienced less hardening than Zircaloy-2 during neutron exposure. The SCC resistance of zirconium-liner cladding was evaluated for failure strains under the tube pressurization SCC test, and compared with the results of Zircaloy-2 cladding. The failure strains of zirconium-liner cladding were significantly larger than those of Zircaloy-2 cladding over all neutron fluence ranges examined, e.g., more than ten times at 1.0 × 10 21n/ cm2 ( E > 1 MeV). Judging from our results on the Vickers microhardness and SCC tests, good SCC resistance of zirconium-liner cladding could be expected even at high fluences.

  12. 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

  13. 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

  14. A fractographic study of iodine-induced stress corrosion cracking in irradiated Zircaloy-2 cladding

    NASA Astrophysics Data System (ADS)

    Shimada, Sachio; Nagai, Masayuki

    1983-02-01

    A fractographic interpretation of stress corrosion cracking (SCC) of Zircaloy-2 was made through detailed scanning electron microscope (SEM) examination of cladding tubes irradiated and subjected to internal pressurization SCC tests in an iodine environment. The SEM examination of the fracture surface revealed that both intergranular and transgranular fracture appeared in the regions of crack initiation. The W-type voids were observed in the intergranular fracture. As the crack proceeded, transgranular fracture, or cleavage facet, became predominant. Cleavage facets were separated by tearing ridges as well as by fluting marks. The appearance of tearing ridges is consistent with the increase of slip systems in α-zirconium with increasing temperature.

  15. Regioselective Lithium-Iodine Exchange-Initiated Cleavage of 2-Iodomethyl-1,3-dioxanes: A Complex-Induced Proximity Effect.

    PubMed

    Bailey, William F; Fair, Justin D

    2016-05-01

    Lithium-iodine exchange-initiated fragmentation of a series of 4-substituted 2-iodomethyl-1,3-dioxanes proceeds rapidly and regioselectively to afford enol ether alcohols by preferential cleavage of the less congested C(2)-O(1) bond. The results demonstrate that a complex-induced proximity effect (CIPE) is likely responsible for the selectivity of the cleavage. PMID:27074433

  16. 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).

  17. 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

  18. 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.

  19. Mechanism of iodine uptake by cabbage: effects of iodine species and where it is stored.

    PubMed

    Weng, Huan-Xin; Hong, Chun-Lai; Yan, Ai-Lan; Pan, Le-Hua; Qin, Ya-Chao; Bao, Lü-Ting; Xie, Ling-Li

    2008-10-01

    Iodine-enhanced vegetable has been proven to be an effective way to reduce iodine deficiency disorders in many regions. However, the knowledge about what mechanisms control plant uptake of iodine and where iodine is stored in plants is still very limited. A series of controlled experiments, including solution culture, pot planting, and field experiments were carried out to investigate the uptake mechanism of iodine in different forms. A new methodology for observing the iodine distribution within the plant tissues, based on AgI precipitation reaction and transmission electron microscope techniques, has been developed and successfully applied to Chinese cabbage. Results show that iodine uptake by Chinese cabbage was more effective when iodine was in the form of IO(3) (-) than in the form of I(-) if the concentration was low (<0.5 mg L(-1)), but the trend was opposite if iodine concentration was 0.5 mg L(-1) or higher. The uptake was more sensitive to metabolism inhibitor in lower concentration of iodine, which implies that the uptake mechanism transits from active to passive as the iodine concentration increases, especially when the iodine is in the form of IO(3) (-). The inorganic iodine fertilizer provided a quicker supply for plant uptake, but the higher level of iodine was toxic to plant growth. The organic iodine fertilizer (seaweed composite) provided a more sustainable iodine supply for plants. Most of the iodine uptake by the cabbage is intercepted and stored in the fibrins in the root while the iodine that is transported to the above-ground portion (shoots and leaves) is selectively stored in the chloroplasts. PMID:18521548

  20. 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

  1. 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

  2. Strategies to Rescue the Consequences of Inducible Arginase-1 Deficiency in Mice

    PubMed Central

    Ballantyne, Laurel L.; Sin, Yuan Yan; St. Amand, Tim; Si, Joshua; Goossens, Steven; Haenebalcke, Lieven; Haigh, Jody J.; Kyriakopoulou, Lianna; Schulze, Andreas; Funk, Colin D.

    2015-01-01

    Arginase-1 catalyzes the conversion of arginine to ornithine and urea, which is the final step of the urea cycle used to remove excess ammonia from the body. Arginase-1 deficiency leads to hyperargininemia in mice and man with severe lethal consequences in the former and progressive neurological impairment to varying degrees in the latter. In a tamoxifen-induced arginase-1 deficient mouse model, mice succumb to the enzyme deficiency within 2 weeks after inducing the knockout and retain <2 % enzyme in the liver. Standard clinical care regimens for arginase-1 deficiency (low-protein diet, the nitrogen-scavenging drug sodium phenylbutyrate, ornithine supplementation) either failed to extend lifespan (ornithine) or only minimally prolonged lifespan (maximum 8 days with low-protein diet and drug). A conditional, tamoxifen-inducible arginase-1 transgenic mouse strain expressing the enzyme from the Rosa26 locus modestly extended lifespan of neonatal mice, but not that of 4-week old mice, when crossed to the inducible arginase-1 knockout mouse strain. Delivery of an arginase-1/enhanced green fluorescent fusion construct by adeno-associated viral delivery (rh10 serotype with a strong cytomegalovirus-chicken β-actin hybrid promoter) rescued about 30% of male mice with lifespan prolongation to at least 6 months, extensive hepatic expression and restoration of significant enzyme activity in liver. In contrast, a vector of the AAV8 serotype driven by the thyroxine-binding globulin promoter led to weaker liver expression and did not rescue arginase-1 deficient mice to any great extent. Since the induced arginase-1 deficient mouse model displays a much more severe phenotype when compared to human arginase-1 deficiency, these studies reveal that it may be feasible with gene therapy strategies to correct the various manifestations of the disorder and they provide optimism for future clinical studies. PMID:25938595

  3. Dietary Zinc Deficiency Exaggerates Ethanol-Induced Liver Injury in Mice: Involvement of Intrahepatic and Extrahepatic Factors

    PubMed Central

    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. PMID:24155903

  4. B-vitamin deficiency is protective against DSS-induced colitis in mice.

    PubMed

    Benight, Nancy M; Stoll, Barbara; Chacko, Shaji; da Silva, Vanessa R; Marini, Juan C; Gregory, Jesse F; Stabler, Sally P; Burrin, Douglas G

    2011-08-01

    Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B(6)-B(12)-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of in vivo Met kinetics using [1-(13)C-methyl-(2)H(3)]methionine infusion in similarly treated mice. Unexpectedly, we found that mice given the B-vitamin-deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF-α and inducible nitric oxide synthase) in the colon in deficient-diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B(6), as markers of B(12) function were only mildly altered. In vivo methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration but increased remethylation. Our findings suggest that disrupted Met metabolism attributable to B(6) deficiency reduces the inflammatory response and disease activity in DSS-challenged mice. These results warrant further human clinical studies to determine whether B(6) deficiency and elevated Hcys in patients with IBD contribute to disease pathobiology. PMID:21596995

  5. The challenges of iodine supplementation: a public health programme perspective.

    PubMed

    Untoro, Juliawati; Timmer, Arnold; Schultink, Werner

    2010-02-01

    An adequate iodine intake during pregnancy, lactation and early childhood is particularly critical for optimal brain development of the foetus and of children 7-24 months of age. While the primary strategy for sustainable elimination of iodine deficiency remains universal salt iodisation, the World Health Organization and the United Nations Children's Fund recommend a complementary strategy of iodine supplements as a temporary measure when salt iodisation could not be implemented. This article aims to review current evidence on efficacy and implications of implementing iodine supplementation as a public health measure to address iodine deficiency. Iodine supplementation seems unlikely to reach high coverage in a rapid, equitable and sustained way. Implementing the programme requires political commitment, effective and efficient supply, distribution and targeting, continuous education and communication and a robust monitoring system. Thus, universal salt iodisation should remain the primary strategy to eliminate iodine deficiency. PMID:20172473

  6. 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.

  7. IEX-1 deficiency induces browning of white adipose tissue and resists diet-induced obesity

    PubMed Central

    Shahid, Mohd; Javed, Ammar A.; Chandra, David; Ramsey, Haley E.; Shah, Dilip; Khan, Mohammed F.; Zhao, Liping; Wu, Mei X.

    2016-01-01

    Chronic inflammation plays a crucial role in the pathogenesis of obesity and insulin resistance. However, the primary mediators that affect energy homeostasis remain ill defined. Here, we report an unexpected role for immediate early response gene X-1 (IEX-1), a downstream target of NF-κB, in energy metabolism. We found that IEX-1 expression was highly induced in white adipose tissue (WAT) in both epidydmal and subcutaneous depots but not in interscapular brown adipose tissue (BAT) in mice fed a high fat diet (HFD). Null mutation of IEX-1 protected mice against HFD-induced adipose and hepatic inflammation, hepatic steatosis, and insulin resistance. Unexpectedly, IEX-1 knockout (IEX-1−/−) mice gained markedly less weight on HFD for 20 weeks as compared to wild-type (WT) littermates (37 ± 3 versus 48 ± 2 gm) due to increased energy expenditure. Mechanistically, we showed that IEX-1 deficiency induced browning and activated thermogenic genes program in WAT but not in BAT by promoting alternative activation of adipose macrophages. Consequently, IEX-1−/− mice exhibited enhanced thermogenesis (24 ± 0.1 versus 22 ± 0.1 kcal/hour/kg in WT mice) explaining increased energy expenditure and lean phenotype in these mice. In conclusion, the present study suggests that IEX-1 is a novel physiological regulator of energy homeostasis via its action in WAT. PMID:27063893

  8. IEX-1 deficiency induces browning of white adipose tissue and resists diet-induced obesity.

    PubMed

    Shahid, Mohd; Javed, Ammar A; Chandra, David; Ramsey, Haley E; Shah, Dilip; Khan, Mohammed F; Zhao, Liping; Wu, Mei X

    2016-01-01

    Chronic inflammation plays a crucial role in the pathogenesis of obesity and insulin resistance. However, the primary mediators that affect energy homeostasis remain ill defined. Here, we report an unexpected role for immediate early response gene X-1 (IEX-1), a downstream target of NF-κB, in energy metabolism. We found that IEX-1 expression was highly induced in white adipose tissue (WAT) in both epidydmal and subcutaneous depots but not in interscapular brown adipose tissue (BAT) in mice fed a high fat diet (HFD). Null mutation of IEX-1 protected mice against HFD-induced adipose and hepatic inflammation, hepatic steatosis, and insulin resistance. Unexpectedly, IEX-1 knockout (IEX-1(-/-)) mice gained markedly less weight on HFD for 20 weeks as compared to wild-type (WT) littermates (37 ± 3 versus 48 ± 2 gm) due to increased energy expenditure. Mechanistically, we showed that IEX-1 deficiency induced browning and activated thermogenic genes program in WAT but not in BAT by promoting alternative activation of adipose macrophages. Consequently, IEX-1(-/-) mice exhibited enhanced thermogenesis (24 ± 0.1 versus 22 ± 0.1 kcal/hour/kg in WT mice) explaining increased energy expenditure and lean phenotype in these mice. In conclusion, the present study suggests that IEX-1 is a novel physiological regulator of energy homeostasis via its action in WAT. PMID:27063893

  9. [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

  10. [Methylenetetrahydrofolate reductase deficiency-induced schizophrenia in a school-age boy].

    PubMed

    Wang, Qiao; Liu, Jing; Liu, Yu-Peng; Li, Xi-Yuan; Ma, Yan-Yan; Wu, Tong-Fei; Ding, Yuan; Song, Jin-Qing; Wang, Yu-Jie; Yang, Yan-Ling

    2014-01-01

    Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. It is known that MTHFR deficiency may result in hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely reported. Here we present the clinical course, biochemical and genetic characteristics of schizophrenia resulted from MTHFR deficiency in a school-age boy. He was 13 years old. He was admitted with a two-year history of fear, auditory hallucination, learning difficulty, sleeping problems, irascibility, drowsing and giggling. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was initiated. After the treatment for 1 week, his plasma and urine levels of homocysteine were decreased to a normal range and the clinical symptoms were significantly improved. After 3 months of treatment, the patient returned to school. He is now living with normal school life. In summary, children with late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to schizophrenia. This rare condition can be early diagnosed through analyses of blood and urine total homocysteine, amino acids in blood and folate in blood and cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin B12 and betaine. PMID:24461181

  11. 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

  12. Interpretation of In-Situ Measurements of Iodine Monoxide in Coastal Regions Using Laser-Induced Fluorescence Spectroscopy

    NASA Astrophysics Data System (ADS)

    Furneaux, K. L.; Whalley, L. K.; Heard, D. E.

    2009-04-01

    Iodine species are present in coastal and open ocean regions due to the release of I2 and iodocarbons from macro and micro algae. The photolysis of these molecules yields iodine atoms, which react with ozone to produce iodine monoxide (IO). IO is involved in ozone depletion cycles, the partitioning of HOx and NOx, and the formation and growth of new particles. A novel point source Laser Induced Fluorescence (LIF) instrument was deployed to measure IO in September 2006 at Roscoff, France as part of the Reactive Halogens in the Marine Boundary Layer (RHaMBLe) programme (1 instrument uncertainty = 23%)1. The maximum IO mixing ratio was 30 ± 7.1 pptV (10 s integration period, limit of detection = 1.4 pptV) at this semi-polluted coastal site (NOx levels = 1 - 5 ppbV). The closest macroalgae beds known to strongly emit I2 (laminaria) were ~ 300 m from the LIF instrument. IO displayed a strong anti-correlation with tidal height which is consistent with previous studies. IO was also dependent on solar irradiation and meteorological conditions. The dominant source of IO at this site was the photolysis of I2. The measurements provided by this instrument aim to address the main uncertainties associated with iodine chemistry. Co-ordinated measurement of IO by point source (LIF) and spatially averaged (Long Path Differential Optical Absorption Spectroscopy) instruments confirm the presence of IO hotspots due to non-uniform macroalgae distribution at this location (resulting in a spatially variable I2 source). The ratio of point source/spatially averaged IO is determined by meteorological conditions and distance of the instrument from macroalgae beds. Co-located point source I2 (Broadband Cavity Ringdown Spectroscopy) and IO (LIF) measurements correlated on some days but cannot be explained by our current knowledge of iodine chemistry. The influence of NOx on IO has been investigated. The detection of IO by LIF at the Roscoff site shows that IO can survive in a high NOx

  13. 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

  14. 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%). PMID:24629671

  15. Inducible Arginase 1 Deficiency in Mice Leads to Hyperargininemia and Altered Amino Acid Metabolism

    PubMed Central

    St. Amand, Tim; Kyriakopoulou, Lianna; Schulze, Andreas; Funk, Colin D.

    2013-01-01

    Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1), which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing “floxed” Arg1 mice with CreERT2 mice. The resulting mice (Arg-Cre) die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency. PMID:24224027

  16. Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.

    PubMed

    Sin, Yuan Yan; Ballantyne, Laurel L; Mukherjee, Kamalika; St Amand, Tim; Kyriakopoulou, Lianna; Schulze, Andreas; Funk, Colin D

    2013-01-01

    Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1), which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2) mice. The resulting mice (Arg-Cre) die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency. PMID:24224027

  17. Utilising cardiopulmonary bypass for cancer surgery. Malignancy-induced protein C deficiency and thrombophilia.

    PubMed

    Marshall, C

    2007-11-01

    Cardiopulmonary bypass has evolved over the last 30 years. It is an important tool for the cardiac surgeon today and also has applications in non-cardiac operations such as surgery to extract tumours. Such patients undergoing surgery for cancer may be at an increased risk of a thromboembolic event post surgery, due to disturbances in the normal clotting pathway leading to hypercoagulability. One such disturbance is malignancy-induced Protein C deficiency. A deficiency of Protein C can cause hypercoagulabitity. Recent studies have examined cardiopulmonary bypass and inherited Protein C deficiency. However, surgery for cancer patients with a malignancy-induced Protein C deficiency involving cardiopulmonary bypass has not been reported. Surgery using CPB in these patients may result in increased morbidity and mortality. The objective of this article is to review the literature in order to discuss the occurrence, the aetiology and possible management of cancer patients with malignancy-induced Protein C deficiencies that require cardiopulmonary bypass for their surgery. PMID:18666739

  18. 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

  19. Endogenous Androgen Deficiency Enhances Diet-Induced Hypercholesterolemia and Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

    PubMed Central

    Hatch, Nicholas W.; Srodulski, Sarah J.; Chan, Huei-Wei; Zhang, Xuan; Tannock, Lisa R.; King, Victoria L.

    2012-01-01

    Background Despite numerous clinical and animal studies, the role of sex steroid hormones on lipoprotein metabolism and atherosclerosis remain controversial. Objective We sought to determine the effects of endogenous estrogen and testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat diet with no added cholesterol. Methods Male and female low-density lipoprotein receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were performed to evaluate the effects of the presence or absence of endogenous hormones on lipid levels, lipoprotein distribution, and atherosclerosis development. Results Female mice fed the study diet for 17 weeks had a marked increase in levels of total cholesterol, triglycerides, apolipoprotein-B containing lipoproteins, and atherosclerosis compared with male mice. Surprisingly, ovariectomy in female mice had no effect on any of these parameters. In contrast, castration of male mice markedly increased total cholesterol concentrations, triglycerides, apolipoprotein B-containing lipoproteins, and atherosclerotic lesion formation compared with male and female mice. Conclusions These data suggest that endogenous androgens protect against diet-induced increases in cholesterol concentrations, formation of proatherogenic lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy, which decreases androgen concentrations, promotes increases in cholesterol concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion formation in lowdensity lipoprotein receptor-deficient mice in response to a low-fat diet. PMID:22981166

  20. Iodine in diet

    MedlinePlus

    ... products also contain iodine. Other good sources are plants grown in iodine-rich soil. ... goiter or hypothyroidism . Without enough iodine, the thyroid ... intake of iodine can reduce the function of the thyroid gland.

  1. 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.

  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. Proton irradiation effect on microstructure, strain localization and iodine-induced stress corrosion cracking in Zircaloy-4

    NASA Astrophysics Data System (ADS)

    Fournier, L.; Serres, A.; Auzoux, Q.; Leboulch, D.; Was, G. S.

    2009-01-01

    The radiation-induced microstructure, strain localization, and iodine-induced stress corrosion cracking (I-SCC) behaviour of recrystallized Zircaloy-4 proton-irradiated to 2 dpa at 305 °C was examined. type dislocation loops having 1/3<1 1 2¯ 0> Burgers vector and a mean diameter and density of, respectively, 10 nm and 17 × 10 21 m -3 were observed while no Zr(Fe,Cr) 2 precipitates amorphization or Fe redistribution were detected after irradiation. After transverse tensile testing to 0.5% macroscopic plastic strain at room temperature, almost exclusively basal channels were imaged. Statistical Schmid factor analysis shows that irradiation leads to a change in slip system activation from prismatic to basal due to a higher increase of critical resolved shear stresses for prismatic slip systems than for basal slip system. Finite element calculations suggest that dislocation channeling occurs in the irradiated proton layer at an equivalent stress close to 70% of the yield stress of the irradiated material, i.e. while the irradiated layer is still in the elastic regime for a 0.5% applied macroscopic plastic strain. Comparative constant elongation rate tensile tests performed at a strain rate of 10 -5 s -1 in iodized methanol solutions at room temperature on specimens both unirradiated and proton-irradiated to 2 dpa demonstrated a detrimental effect of irradiation on I-SCC.

  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. 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

  6. 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.

  7. Lesions of the entopeduncular nucleus in rats prevent apomorphine-induced deficient sensorimotor gating.

    PubMed

    Lütjens, Götz; Krauss, Joachim K; Schwabe, Kerstin

    2011-07-01

    Dopamine-induced hyperactivity and deficient sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR), are used as animal models for neuropsychiatric disorders such as schizophrenia and Tourette's syndrome. We here investigated whether excitotoxic lesions of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), would improve apomorphine-induced PPI-deficits and hyperactivity. Additionally, we investigated the effect of EPN lesions on cognition, motivation and motor skills. In male Sprague Dawley rats bilateral EPN lesions were induced by stereotactic injection of ibotenate (4 μg in 0.4 μl phosphate buffered saline, PBS) or sham-lesions by injection of vehicle PBS. After one week, rats were tested for learning and memory (continuous and delayed alternation, T-maze), for motivation (progressive ratio test with breakpoint of 3 min inactivity, Skinner box), and for motor skills (rotating rod). Thereafter, rats were tested for PPI of ASR (startle response system) after subcutaneous injection of apomorphine (1.0mg/kg and vehicle) and for locomotor activity (0.5mg/kg and vehicle). Ibotenate-induced EPN lesions did not affect learning and memory, motivation or motor skills. Basal locomotor activity and PPI was also not affected, but EPN lesions ameliorated apomorphine-induced hyperlocomotion and deficient PPI. This work indicates an important role of the EPN for the modulation of dopamine agonist-induced deficient sensorimotor gating and hyperlocomotion, without affecting normal behavioral function. PMID:21315767

  8. 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

  9. The Vacuolar Manganese Transporter MTP8 Determines Tolerance to Iron Deficiency-Induced Chlorosis in Arabidopsis.

    PubMed

    Eroglu, Seckin; Meier, Bastian; von Wirén, Nicolaus; Peiter, Edgar

    2016-02-01

    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

  10. Heme deficiency of soluble guanylate cyclase induces gastroparesis

    PubMed Central

    COSYNS, S. M. R.; DHAESE, I.; THOONEN, R.; BUYS, E. S.; VRAL, A.; BROUCKAERT, P.; LEFEBVRE, R. A.

    2016-01-01

    Background Soluble guanylate cyclase (sGC) is the principal target of nitric oxide (NO) to control gastrointestinal motility. The consequence on nitrergic signaling and gut motility of inducing a heme-free status of sGC, as induced by oxidative stress, was investigated. Methods sGCβ1H105F knock-in (apo-sGC) mice, which express heme-free sGC that has basal activity, but cannot be stimulated by NO, were generated. Key Results Diethylenetriamine NONOate did not increase sGC activity in gastrointestinal tissue of apo-sGC mice. Exogenous NO did not induce relaxation in fundic, jejunal and colonic strips, and pyloric rings of apo-sGC mice. The stomach was enlarged in apo-sGC mice with hypertrophy of the muscularis externa of the fundus and pylorus. In addition, gastric emptying and intestinal transit were delayed and whole-gut transit time was increased in the apo-sGC mice, while distal colonic transit time was maintained. The nitrergic relaxant responses to electrical field stimulation at 1–4 Hz were abolished in fundic and jejunal strips from apo-sGC mice, but in pyloric rings and colonic strips, only the response at 1 Hz was abolished, indicating the contribution of other transmitters than NO. Conclusions & Inferences The results indicate that the gastrointestinal consequences of switching from a native sGC to a heme-free sGC, which cannot be stimulated by NO, are most pronounced at the level of the stomach establishing a pivotal role of the activation of sGC by NO in normal gastric functioning. In addition, delayed intestinal transit was observed, indicating that nitrergic activation of sGC also plays a role in the lower gastrointestinal tract. PMID:23551931

  11. 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

  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. 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

  14. 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

  15. 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

  16. 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

  17. Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment

    PubMed Central

    Sartori, S.B.; Whittle, N.; Hetzenauer, A.; Singewald, N.

    2012-01-01

    Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg2+) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg2+ modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg2+ deficiency and whether Mg2+ deficiency is associated with altered HPA axis function. Compared with controls, Mg2+ deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg2+ deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg2+ deficiency caused an increase in the transcription of the corticotropin releasing hormone in the paraventricular hypothalamic nucleus (PVN), and elevated ACTH plasma levels, pointing to an enhanced set-point of the HPA axis. Chronic treatment with desipramine reversed the identified abnormalities of the stress axis. Functional mapping of neuronal activity using c-Fos revealed hyper-excitability in the PVN of anxious Mg2+ deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg2+ deficiency model as a mouse model of enhanced anxiety, showing sensitivity to treatment with anxiolytics and antidepressants. It is further suggested that dysregulations in the HPA axis may contribute to the hyper-emotionality in response to dietary induced hypomagnesaemia. This article is part of a Special Issue entitled ‘Anxiety and Depression’. PMID:21835188

  18. Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment.

    PubMed

    Sartori, S B; Whittle, N; Hetzenauer, A; Singewald, N

    2012-01-01

    Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg(2+)) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg(2+) modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg(2+) deficiency and whether Mg(2+) deficiency is associated with altered HPA axis function. Compared with controls, Mg(2+) deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg(2+) deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg(2+) deficiency caused an increase in the transcription of the corticotropin releasing hormone in the paraventricular hypothalamic nucleus (PVN), and elevated ACTH plasma levels, pointing to an enhanced set-point of the HPA axis. Chronic treatment with desipramine reversed the identified abnormalities of the stress axis. Functional mapping of neuronal activity using c-Fos revealed hyper-excitability in the PVN of anxious Mg(2+) deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg(2+) deficiency model as a mouse model of enhanced anxiety, showing sensitivity to treatment with anxiolytics and antidepressants. It is further suggested that dysregulations in the HPA axis may contribute to the hyper-emotionality in response to dietary induced hypomagnesaemia. This article is part of a Special Issue entitled 'Anxiety and Depression'. PMID:21835188

  19. 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.

  20. ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage

    PubMed Central

    Kessel, David H.; Price, Michael; Reiners, Jr., John J.

    2012-01-01

    Photodynamic therapy (PDT) involves photosensitizing agents that, in the presence of oxygen and light, initiate formation of cytotoxic reactive oxygen species (ROS). PDT commonly induces both apoptosis and autophagy. Previous studies with murine hepatoma 1c1c7 cells indicated that loss of autophagy-related protein 7 (ATG7) inhibited autophagy and enhanced the cytotoxicity of photosensitizers that mediate photodamage to mitochondria or the endoplasmic reticulum. In this study, we examined two photosensitizing agents that target lysosomes: the chlorin NPe6 and the palladium bacteriopheophorbide WST11. Irradiation of wild-type 1c1c7 cultures loaded with either photosensitizer induced apoptosis and autophagy, with a blockage of autophagic flux. An ATG7- or ATG5-deficiency suppressed the induction of autophagy in PDT protocols using either photosensitizer. Whereas ATG5-deficient cells were quantitatively similar to wild-type cultures in their response to NPe6 and WST11 PDT, an ATG7-deficiency suppressed the apoptotic response (as monitored by analyses of chromatin condensation and procaspase-3/7 activation) and increased the LD50 light dose by > 5-fold (as monitored by colony-forming assays). An ATG7-deficiency did not prevent immediate lysosomal photodamage, as indicated by loss of the lysosomal pH gradient. However, unlike wild-type and ATG5-deficient cells, the lysosomes of ATG7-deficient cells recovered this gradient within 4 h of irradiation, and never underwent permeabilization (monitored as release of endocytosed 10-kDa dextran polymers). We propose that the efficacy of lysosomal photosensitizers is in part due to both promotion of autophagic stress and suppression of autophagic prosurvival functions. In addition, an effect of ATG7 unrelated to autophagy appears to modulate lysosomal photodamage. PMID:22889762

  1. 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.

  2. 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

  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. DNA and chromosome breaks induced by iodine-123-labeled estrogen in Chinese hamster ovary cells

    SciTech Connect

    Schwartz, J.L. |; Mustafi, R.; Hughes, A.; DeSombre, E.R.

    1996-08-01

    The effects of the Auger electron-emitting isotope {sup 123}I, covalently bound to estrogen, on DNA single- and double-strand breakage and on chromosome breakage was determined in estrogen receptor-positive Chinese hamster ovary (CHO-ER) cells. Exposure to the {sup 123}I-labeled estrogen induced both single- and double-strand breaks with a ratio of single- to double-strand breaks of 2.8. The corresponding ratio with {sup 60}Co {gamma} rays was 15.6. The dose response was biphasic, suggesting either that receptor sites are saturated at high doses, or that there is a nonrandom distribution of breaks induced by the {sup 123}I-labeled estrogen. The {sup 123}I-labeled estrogen treatment induced chromosome aberrations with an efficiency of about 1 aberration for each 1000 disintegrations per cell. This corresponds to the mean lethal dose of {sup 123}I-labeled estrogen for these cells, suggesting that the lethal event induced by the Auger electron emitter bound to estrogen is a chromosome aberration. Most of the chromosome-type aberrations were dicentrics and rings, suggesting that {sup 123}I-labeled estrogen-induced chromosome breaks are rejoined. The F ratio, the ratio of dicentrics to centric rings, was 5.8 {+-} 1.7, which is similar to that seen with high-LET radiations. Our results suggest that {sup 123}I bound to estrogen is an efficient clastogenic agent, the cytotoxic damage produced by {sup 123}I bound to estrogen is very like damage induced by high-LET radiation, and the {sup 123}I in the estrogen receptor-DNA complex is probably in proximity to the sugar-phosphate backbone of the DNA. 40 refs., 7 figs.

  5. 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

  6. Chop Deficiency Protects Mice Against Bleomycin-induced Pulmonary Fibrosis by Attenuating M2 Macrophage Production.

    PubMed

    Yao, Yingying; Wang, Yi; Zhang, Zhijun; He, Long; Zhu, Jianghui; Zhang, Meng; He, Xiaoyu; Cheng, Zhenshun; Ao, Qilin; Cao, Yong; Yang, Ping; Su, Yunchao; Zhao, Jianping; Zhang, Shu; Yu, Qilin; Ning, Qin; Xiang, Xudong; Xiong, Weining; Wang, Cong-Yi; Xu, Yongjian

    2016-05-01

    C/EBP homologous protein (Chop) has been shown to have altered expression in patients with idiopathic pulmonary fibrosis (IPF), but its exact role in IPF pathoaetiology has not been fully addressed. Studies conducted in patients with IPF and Chop(-/-) mice have dissected the role of Chop and endoplasmic reticulum (ER) stress in pulmonary fibrosis pathogenesis. The effect of Chop deficiency on macrophage polarization and related signalling pathways were investigated to identify the underlying mechanisms. Patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis were affected by the altered Chop expression and ER stress. In particular, Chop deficiency protected mice against BLM-induced lung injury and fibrosis. Loss of Chop significantly attenuated transforming growth factor β (TGF-β) production and reduced M2 macrophage infiltration in the lung following BLM induction. Mechanistic studies showed that Chop deficiency repressed the M2 program in macrophages, which then attenuated TGF-β secretion. Specifically, loss of Chop promoted the expression of suppressors of cytokine signaling 1 and suppressors of cytokine signaling 3, and through which Chop deficiency repressed signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma signaling, the essential pathway for the M2 program in macrophages. Together, our data support the idea that Chop and ER stress are implicated in IPF pathoaetiology, involving at least the induction and differentiation of M2 macrophages. PMID:26883801

  7. Differential responses in pear and quince genotypes induced by Fe deficiency and bicarbonate.

    PubMed

    Donnini, Silvia; Castagna, Antonella; Ranieri, Annamaria; Zocchi, Graziano

    2009-07-15

    Most of the studies carried out on Fe deficiency condition in arboreous plants have been performed, with the exception of those carried out on plants grown in the field, in hydroponic culture utilizing a total iron depletion growth condition. This can cause great stress to plants. By introducing Fe deficiency induced by the presence of bicarbonate, we found significant differences between Pyrus communis L. cv. Conference and Cydonia oblonga Mill. BA29 and MA clones, characterized by different levels of tolerance to chlorosis. Pigment content and the main protein-pigment complexes were investigated by HPLC and protein gel blot analysis, respectively. While similar changes in the structural organization of photosystems (PSs) were observed in both species under Fe deficiency, a different reorganization of the photosynthetic apparatus was found in the presence of bicarbonate between tolerant and susceptible genotypes, in agreement with the photosynthetic electron transport rate measured in isolated thylakoids. In order to characterize the intrinsic factors determining the efficiency of iron uptake in a tolerant genotype, the main mechanisms induced by Fe deficiency in Strategy I species, such as Fe3+-chelate reductase (EC 1.16.1.7) and H+-ATPase (EC 3.6.3.6) activities, were also investigated. We demonstrate that physiological and biochemical root responses in quince and pear are differentially affected by iron starvation and bicarbonate supply, and we show a high correlation between tolerance and Strategy I activation. PMID:19269060

  8. 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. PMID:26212983

  9. Reduced early alcohol-induced liver injury in CD14-deficient mice.

    PubMed

    Yin, M; Bradford, B U; Wheeler, M D; Uesugi, T; Froh, M; Goyert, S M; Thurman, R G

    2001-04-01

    Activation of Kupffer cells by gut-derived endotoxin is associated with alcohol-induced liver injury. Recently, it was shown that CD14-deficient mice are more resistant to endotoxin-induced shock than wild-type controls. Therefore, this study was designed to investigate the role of CD14 receptors in early alcohol-induced liver injury using CD14 knockout and wild-type BALB/c mice in a model of enteral ethanol delivery. Animals were given a high-fat liquid diet continuously with ethanol or isocaloric maltose-dextrin as control for 4 wk. The liver to body weight ratio in wild-type mice (5.8 +/- 0.3%) was increased significantly by ethanol (7.3 +/- 0.2%) but was not altered by ethanol in CD14-deficient mice. Ethanol elevated serum alanine aminotransferase levels nearly 3-fold in wild-type mice, but not in CD14-deficient mice. Wild-type and knockout mice given the control high-fat diet had normal liver histology, whereas ethanol caused severe liver injury (steatosis, inflammation, and necrosis; pathology score = 3.8 +/- 0.4). In contrast, CD14-deficient mice given ethanol showed minimal hepatic changes (score = 1.6 +/- 0.3, p < 0.05). Additionally, NF-kappa B, TGF-beta, and TNF-alpha were increased significantly in wild-type mice fed ethanol but not in the CD14 knockout. Thus, chronic ethanol feeding caused more severe liver injury in wild-type than CD14 knockouts, supporting the hypothesis that endotoxin acting via CD14 plays a major role in the development of early alcohol-induced liver injury. PMID:11254735

  10. Dietary Deficiency of Essential Amino Acids Rapidly Induces Cessation of the Rat Estrous Cycle

    PubMed Central

    Bannai, Makoto; Ichimaru, Toru; Nakano, Sayako; Murata, Takuya; Higuchi, Takashi; Takahashi, Michio

    2011-01-01

    Reproductive functions are regulated by the sophisticated coordination between the neuronal and endocrine systems and are sustained by a proper nutritional environment. Female reproductive function is vulnerable to effects from dietary restrictions, suggesting a transient adaptation that prioritizes individual survival over reproduction until a possible future opportunity for satiation. This adaptation could also partially explain the existence of amenorrhea in women with anorexia nervosa. Because amino acid nutritional conditions other than caloric restriction uniquely alters amino acid metabolism and affect the hormonal levels of organisms, we hypothesized that the supply of essential amino acids in the diet plays a pivotal role in the maintenance of the female reproductive system. To test this hypothesis, we examined ovulatory cyclicity in female rats under diets that were deficient in threonine, lysine, tryptophan, methionine or valine. Ovulatory cyclicity was monitored by daily cytological evaluations of vaginal smears. After continuous feeding of the deficient diet, a persistent diestrus or anovulatory state was induced most quickly by the valine-deficient diet and most slowly by the lysine-deficient diet. A decline in the systemic insulin-like growth factor 1 level was associated with a dietary amino acid deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet with balanced amino acids maintained normal estrous cyclicity. These disturbances of the estrous cycle by amino acid deficiency were quickly reversed by the consumption of a normal diet. The continuous anovulatory state in this study is not attributable to a decrease in caloric intake but to an imbalance in the dietary amino acid composition. With a shortage of well-balanced amino acid sources, reproduction becomes risky for both the mother and the fetus. It could be viewed as an adaptation to the diet, diverting resources away from reproduction and reallocating them to

  11. 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.

  12. 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

  13. 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

  14. 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

  15. [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

  16. AMP-Activated Protein Kinase Deficiency Exacerbates Aging-Induced Myocardial Contractile Dysfunction

    PubMed Central

    Turdi, Subat; Fan, Xiujuan; Li, Ji; Zhao, Junxing; Huff, Anna F.; Du, Min; Ren, Jun

    2010-01-01

    Aging is associated with myocardial dysfunction although the underlying mechanism is unclear. AMPK, a key cellular fuel sensor for energy metabolism, is compromised with aging. This study examined the role of AMPK deficiency in aging-associated myocardial dysfunction. Young or old minwild-type (WT) and transgenic mice with overexpression of a mutant AMPK α2 subunit (kinase dead, KD) were used. AMPK α isoform activity, myocardial function and morphology were examined. DCF and JC-1 fluorescence probes were employed to quantify reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm), respectively. KD mice displayed significantly reduced α2 but not α1 AMPK isoform activity at both ages with a greater effect at old age. Aging itself decreased α1 isoform activity. Cardiomyocyte contractile function, intracellular Ca2+ handling and SERCA2a levels were compromised with aging, the effects of which were exacerbated by AMPK deficiency. H&E staining revealed cardiomyocyte hypertrophy with aging, which was more pronounced in KD mice. TEM micrographs displayed severe disruption of mitochondrial ultrastructure characterized by swollen, irregular shape and disrupted cristae in aged KD compared with WT mice. Aging enhanced ROS production and reduced ΔΨm, the effects of which were accentuated by AMPK deficiency. Immunoblotting data depicted unchanged Akt phosphorylation and a significant decrease in mitochondrial biogenesis cofactor PGC-1α in aged groups. AMPK deficiency but not aging decreased the phosphorylation of ACC and eNOS. Expression of membrane Glut4 and HSP90 was decreased in aged KD mice. Moreover, treatment of the AMPK activator metformin attenuated aging-induced cardiomyocyte contractile defects. Collectively, our data suggest a role for AMPK deficiency in aging-induced cardiac dysfunction possibly through disrupted mitochondrial function and ROS production. PMID:20477759

  17. Pancreas Recovery Following Caerulein-induced Pancreatitis is Impaired in Plasminogen Deficient Mice

    PubMed Central

    Lugea, Aurelia; Nan, Li; French, Samuel W.; Bezerra, Jorge A.; Gukovskaya, Anna S; Pandol, Stephen J.

    2006-01-01

    Background & Aims: The plasminogen (plg) system participates in tissue repair in several organs, but its role in pancreas repair remains poorly characterized. To better understand the role of plg in pancreas recovery following injury, we examined the course of caerulein-induced pancreatitis in plg deficient and sufficient mice. Methods: Pancreatitis was induced by caerulein administration (50 μg/kg, 7 ip injections). Mice were sacrificed either at the acute phase (7 hours after the first caerulein injection) or during recovery (at 2, 4 and 7 days). In pancreatic sections we examined: pancreatic morphology, trypsin activation, inflammatory cell infiltration, acinar cell death, cell proliferation, extracellular matrix (ECM) deposition, activation of stellate cells (PSCs), and components of the plg and metalloproteinase systems. Results: In plg sufficient mice, pancreatic plg levels and plasmin activity increased during the acute phase and remained elevated during recovery. Pancreatitis resolved in plg sufficient mice within 7 days. Pancreas recovery involved reorganization of the parenchyma structure, removal of necrotic debris, cell proliferation, transient activation of PSCs and moderate deposition of ECM proteins. Acute pancreatitis (7-h) was indistinguishable between plg deficient and sufficient mice. In contrast, pancreas recovery was impaired in plg deficient mice. Plg deficiency led to disorganized parenchyma, extensive acinar cell loss, poor removal of necrotic debris, reduced cell proliferation and fibrosis. Fibrosis was characterized by deposition of collagens and fibronectin, persistent activation of PSCs and upregulation of pancreatic TGF-β1. Conclusions: Plg/plasmin deficiency leads to features similar to those found in chronic pancreatitis such as parenchymal atrophy and fibrosis. PMID:16952557

  18. 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. PMID:26659808

  19. Nitric oxide is involved in phosphorus deficiency-induced cluster root development and citrate exudation in white lupin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White lupin (Lupinus albus) forms specialized cluster roots characterized by exudation of organic anions under phosphorus (P) deficiency. Here, we evaluated the role of nitric oxide (NO) in P deficiency-induced cluster-root formation and citrate exudation in white lupin. Plants were treated with NO ...

  20. 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

  1. 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

  2. Thiamin deficiency impairs endotoxin-induced increases in hepatic glucose output.

    PubMed

    Molina, P E; Yousef, K A; Smith, R M; Tepper, P G; Lang, C H; Abumrad, N N

    1994-05-01

    We addressed the role of thiamin, a cofactor for several enzymes involved in glucose metabolism, in the glucose metabolic response to endotoxin. Characterized by hyperglycemia, increased hepatic glucose production exceeding elevated rates of whole-body glucose utilization, this response is mediated by hormones and cytokines and is dependent on the immune and nutritional status of the host. We hypothesized that a thiamin-deficient state would impair the metabolic response to endotoxin. Rats were fed a thiamin-deficient or control diet for 6 wk before in vivo assessment of glucose kinetics. In control rats, Escherichia coli endotoxin increased the rate of glucose appearance (+76%), disappearance (+70%), and metabolic clearance (+50%). Thiamin deficiency resulted in increased plasma glucose (18%) and lactate (3- to 4-fold) as well as in a 30% decrease in insulin and an increase in glucagon (2.6-fold) and corticosterone (3.6-fold). Thiamin deficiency inhibited the endotoxin-induced hyperglycemia and the rise in hepatic glucose production, glucose utilization, and metabolic clearance rate. PMID:8172089

  3. Vitamin d deficiency attenuates high-fat diet-induced hyperinsulinemia and hepatic lipid accumulation in male mice.

    PubMed

    Liu, Xiao-Jing; Wang, Bi-Wei; Zhang, Cheng; Xia, Mi-Zhen; Chen, Yuan-Hua; Hu, Chun-Qiu; Wang, Hua; Chen, Xi; Xu, De-Xiang

    2015-06-01

    It is increasingly recognized that vitamin D deficiency is associated with increased risks of metabolic disorders among overweight children. A recent study showed that vitamin D deficiency exacerbated inflammation in nonalcoholic fatty liver disease through activating toll-like receptor 4 in a high-fat diet (HFD) rat model. The present study aimed to further investigate the effects of vitamin D deficiency on HFD-induced insulin resistance and hepatic lipid accumulation. Male ICR mice (35 d old) were randomly assigned into 4 groups as follows. In control diet and vitamin D deficiency diet (VDD) groups, mice were fed with purified diets. In HFD and VDD+HFD groups, mice were fed with HFD. In VDD and VDD+HFD groups, vitamin D in feed was depleted. Feeding mice with vitamin D deficiency diet did not induce obesity, insulin resistance, and hepatic lipid accumulation. By contrary, vitamin D deficiency markedly alleviated HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated HFD-induced up-regulation of hepatic peroxisome proliferator-activated receptor γ, which promoted hepatic lipid uptake and lipid droplet formation, and its target gene cluster of differentiation 36. In addition, vitamin D deficiency up-regulated carnitine palmitoyltrans 2, the key enzyme for fatty acid β-oxidation, and uncoupling protein 3, which separated oxidative phosphorylation from ATP production, in adipose tissue. These data suggest that vitamin D deficiency is not a direct risk factor for obesity, insulin resistance, and hepatic lipid accumulation. Vitamin D deficiency alleviates HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation through promoting fatty acid β-oxidation and elevating energy expenditure in adipose tissue. PMID:25774554

  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. In-situ measurements of iodine monoxide at coastal and open-ocean locations using laser induced fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Commane, R.; Whalley, L. K.; Furneaux, K. L.; Ingham, T.; Bloss, W. J.; Heard, D. E.

    2008-12-01

    The halogen oxides, IO and BrO, have traditionally been measured using the Long Path-Differential Optical Absorption Spectroscopy (LP-DOAS) technique. Laser Induced Fluorescence (LIF), however, provides a sensitive and selective alternative method to detect IO. LIF provides a point-source measurement of IO; comparison of IO data taken using LIF and LP-DOAS can help determine local sources of iodine at coastal sites. In-situ techniques, such as LIF, also allow a direct comparison with other co-located in-situ instruments, improving the understanding of the chemical interactions that occur. Furthermore the size, weight and flexibility of such instruments mean that they are readily deployable on ship and aircraft platforms, as well as at ground-based sites. The University of Leeds LIF-IO instruments have been operational since 2006; data taken at three contrasting locations will be presented. IO measurements were made at the Mace Head Observatory on the west coast of Ireland in 2007. The site is predominantly impacted by background air-masses from the north Atlantic. An anti-correlation between IO concentration and tidal height during the day was observable; a maximum of 33 pptV was observed during the lowest tides. A comparison with concurrent LP-DOAS measurements demonstrates local hot-spots of IO production. The release of I2 from a narrow strip of macro-algae, specifically laminaria, along this coastline acts as the major iodine source. In-situ IO measurements were also made at a second coastal site, in Roscoff, France as part of the Reactive Halogens in the Marine Boundary Layer (RHaMBLe) project. This stretch of coastline is also impacted by macro-algae and high concentrations of IO were again observable at low-tide. In contrast to Mace Head, the Roscoff site was influenced by local pollution. A negative correlation between IO and NO2 was observed during low-tide periods; a positive correlation between IO and new particle bursts was also recorded. This work

  6. Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells

    PubMed Central

    Shi, Xiaoli; Deng, Haohua; Dai, Zhe; Xu, Yancheng; Xiong, Xiaokan; Ma, Pei; Cheng, Jing

    2016-01-01

    Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes. PMID:26649147

  7. Effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat

    SciTech Connect

    Barton, R.W.

    1985-10-15

    Inherited deficiency of the enzyme adenosine deaminase (ADA) has been found in a significant proportion of patients with severe combined immunodeficiency disease and inherited defect generally characterized by a deficiency of both B and T cells. Two questions are central to understanding the pathophysiology of this disease: (1) at what stage or stages in lymphocyte development are the effects of the enzyme deficiency manifested; (2) what are the biochemical mechanisms responsible for the selective pathogenicity of the lymphoid system. We have examined the stage or stages of rat T-cell development in vivo which are affected by an induced adenosine deaminase deficiency using the ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2'-deoxycoformycin (DCF). In normal rats given daily administration of an ADA inhibitor, cortical thymocytes were markedly depleted; peripheral lymphocytes and pluripotent hemopoietic stem cells (CFU-S) all were relatively unaffected. Since a deficiency of ADA affects lymphocyte development, the regeneration of cortical and medullary thymocytes and their precursors after sublethal irradiation was used as a model of lymphoid development. By Day 5 after irradiation the thymus was reduced to 0.10-0.5% of its normal size; whereas at Days 9 and 14 the thymus was 20-40% and 60-80% regenerated, respectively. When irradiated rats were given daily parenteral injections of the ADA inhibitor plus adenosine or deoxyadenosine, thymus regeneration at Days 9 and 14 was markedly inhibited, whereas the regeneration of thymocyte precursors was essentially unaffected. Thymus regeneration was at least 40-fold lower than in rats given adenosine or deoxyadenosine alone. Virtually identical results were obtained with both ADA inhibitors, EHNA and DCF.

  8. 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. PMID:26562264

  9. Intranasal peptide-induced tolerance and linked suppression: consequences of complement deficiency.

    PubMed

    Fossati-Jimack, Liliane; Ling, Guang Sheng; Baudino, Lucie; Szajna, Marta; Manivannan, Kiruthika; Zhao, Jade Chen; Midgley, Robert; Chai, Jian-Guo; Simpson, Elizabeth; Botto, Marina; Scott, Diane

    2015-01-01

    A role for complement, particularly the classical pathway, in the regulation of immune responses is well documented. Deficiencies in C1q or C4 predispose to autoimmunity, while deficiency in C3 affects the suppression of contact sensitization and generation of oral tolerance. Complement components including C3 have been shown to be required for both B-cell and T-cell priming. The mechanisms whereby complement can mediate these diverse regulatory effects are poorly understood. Our previous work, using the mouse minor histocompatibility (HY) model of skin graft rejection, showed that both C1q and C3 were required for the induction of tolerance following intranasal peptide administration. By comparing tolerance induction in wild-type C57BL/6 and C1q-, C3-, C4- and C5-deficient C57BL/6 female mice, we show here that the classical pathway components including C3 are required for tolerance induction, whereas C5 plays no role. C3-deficient mice failed to generate a functional regulatory T (Treg) -dendritic cell (DC) tolerogenic loop required for tolerance induction. This was related to the inability of C3-deficient DC to up-regulate the arginine-consuming enzyme, inducible nitric oxide synthase (Nos-2), in the presence of antigen-specific Treg cells and peptide, leading to reduced Treg cell generation. Our findings demonstrate that the classical pathway and C3 play a critical role in the peptide-mediated induction of tolerance to HY by modulating DC function. PMID:25039245

  10. Intranasal peptide-induced tolerance and linked suppression: consequences of complement deficiency

    PubMed Central

    Fossati-Jimack, Liliane; Ling, Guang Sheng; Baudino, Lucie; Szajna, Marta; Manivannan, Kiruthika; Zhao, Jade Chen; Midgley, Robert; Chai, Jian-Guo; Simpson, Elizabeth; Botto, Marina; Scott, Diane

    2015-01-01

    A role for complement, particularly the classical pathway, in the regulation of immune responses is well documented. Deficiencies in C1q or C4 predispose to autoimmunity, while deficiency in C3 affects the suppression of contact sensitization and generation of oral tolerance. Complement components including C3 have been shown to be required for both B-cell and T-cell priming. The mechanisms whereby complement can mediate these diverse regulatory effects are poorly understood. Our previous work, using the mouse minor histocompatibility (HY) model of skin graft rejection, showed that both C1q and C3 were required for the induction of tolerance following intranasal peptide administration. By comparing tolerance induction in wild-type C57BL/6 and C1q-, C3-, C4- and C5-deficient C57BL/6 female mice, we show here that the classical pathway components including C3 are required for tolerance induction, whereas C5 plays no role. C3-deficient mice failed to generate a functional regulatory T (Treg) –dendritic cell (DC) tolerogenic loop required for tolerance induction. This was related to the inability of C3-deficient DC to up-regulate the arginine-consuming enzyme, inducible nitric oxide synthase (Nos-2), in the presence of antigen-specific Treg cells and peptide, leading to reduced Treg cell generation. Our findings demonstrate that the classical pathway and C3 play a critical role in the peptide-mediated induction of tolerance to HY by modulating DC function. PMID:25039245

  11. Surgical treatment for a paraplegic patient induced by congenital factor X deficiency

    PubMed Central

    Lin, Weicheng; Zhou, Jing; Wang, Tianbing; Zhang, Peixun

    2015-01-01

    Congenital factor X (FX) deficiency is a rare disease which usually leads to coagulation disorders. We reported a case of paraplegic patient induced by traumatic spinal epidural hematoma which was associated with congenital FX deficiency. The treatments of this patient included elevating FX activity (FX: C) by adding fresh-frozen plasma (FFP) or prothrombin complex concentration (PCC) to improve his coagulation function, and doing operation to remove his spinal hematoma. Symptoms started to resolve after operation. Besides, we found one of his elder brother had the same disease as the patient himself via family follow-up. They can survive because their FX: C are relatively high enough to keep them away from fatal bleeding. PMID:26550274

  12. Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice

    PubMed Central

    Sun, Der-Shan; Lee, Po-Chien; Kau, Jyh-Hwa; Shih, Yung-Luen; Huang, Hsin-Hsien; Li, Chen-Ru; Lee, Chin-Cheng; Wu, Yu-Ping; Chen, Kuo-Ching; Chang, Hsin-Hou

    2015-01-01

    Mice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-of-function approach involving injections of recombinant FVIII to complement the coagulation deficiency should ameliorate the pathogenesis. As expected, a sublethal dose of LT caused mortality in the mice that were non-lethally pretreated with an anticoagulant (warfarin). By contrast, treatments of recombinant FVIII reduced the mortality from a lethal dose of LT in mice. Our results indicated that LT-induced deficiency of FVIII is involved in LT-mediated pathogenesis. Using recombinant FVIII to correct the coagulant defect may enable developing a new strategy to treat anthrax. PMID:25906166

  13. 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

  14. Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice.

    PubMed

    Sun, Der-Shan; Lee, Po-Chien; Kau, Jyh-Hwa; Shih, Yung-Luen; Huang, Hsin-Hsien; Li, Chen-Ru; Lee, Chin-Cheng; Wu, Yu-Ping; Chen, Kuo-Ching; Chang, Hsin-Hou

    2015-01-01

    Mice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-of-function approach involving injections of recombinant FVIII to complement the coagulation deficiency should ameliorate the pathogenesis. As expected, a sublethal dose of LT caused mortality in the mice that were non-lethally pretreated with an anticoagulant (warfarin). By contrast, treatments of recombinant FVIII reduced the mortality from a lethal dose of LT in mice. Our results indicated that LT-induced deficiency of FVIII is involved in LT-mediated pathogenesis. Using recombinant FVIII to correct the coagulant defect may enable developing a new strategy to treat anthrax. PMID:25906166

  15. 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

  16. 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. PMID:23108647

  17. The impact of FANCD2 deficiency on formaldehyde-induced toxicity in human lymphoblastoid cell lines

    PubMed Central

    Ren, Xuefeng; Ji, Zhiying; McHale, Cliona M.; Yuh, Jessica; Bersonda, Jessica; Tang, Maycky; Smith, Martyn T.; Zhang, Luoping

    2015-01-01

    Formaldehyde (FA), a major industrial chemical and ubiquitous environmental pollutant, has recently been classified by the International Agency for Research on Cancer as a human leukemogen. The major mode of action of FA is thought to be the formation of DNA-protein crosslinks (DPCs). Repair of DPCs may be mediated by the Fanconi anemia pathway; however, data supporting the involvement of this pathway is limited, particularly in human hematopoietic cells. Therefore, we assessed the role of FANCD2, a critical component of the Fanconi anemia pathway, in FA-induced toxicity in human lymphoblast cell models of FANCD2-deficiency (PD20 cells) and FANCD2-sufficiency (PD20-D2 cells). After treatment of the cells with 0-150 μM FA for 24 hours, DPCs were increased in a dose-dependent manner in both cell lines, with greater increases in FANCD2-deficient PD20 cells. FA also induced cytotoxicity, micronuclei, chromosome aberrations, and apoptosis in a dose-dependent manner in both cell lines, with greater increases in cytotoxicity and apoptosis in PD20 cells. Increased levels of γ-ATR and γ-H2AX in both cell lines suggested the recognition of FA-induced DNA damage; however, the induction of BRCA2 was compromised in FANCD2-deficient PD20 cells, potentially reducing the capacity to repair DPCs. Together, these findings suggest that FANCD2 protein and the Fanconi anemia pathway are essential to protect human lymphoblastoid cells against FA toxicity. Future studies are needed to delineate the role of this pathway in mitigating FA-induced toxicity, particularly in hematopoietic stem cells, the target cells in leukemia. PMID:22872141

  18. Autophagy deficiency in β cells blunts incretin-induced suppression of glucagon release from α cells.

    PubMed

    Kim, Min Joo; Choi, Ok Kyong; Chae, Kyung Sil; Lee, Hakmo; Chung, Sung Soo; Ham, Dong-Sik; Kim, Ji-Won; Yoon, Kun-Ho; Park, Kyong Soo; Jung, Hye Seung

    2015-09-01

    Incretin-based therapy such as GLP-1 receptor agonists and DPP-4 inhibitors for type 2 diabetes mellitus is characterized by glucose-dependent insulin secretion and glucose-inhibited glucagon secretion. Recently, autophagy deficiency in islet β cells has been shown to contribute to the pathogenesis of type 2 diabetes mellitus however, with the role of incretin has not been established. To evaluate the role of autophagy in incretin effects, 8-week-old male β cell-specific Atg7 knockout (Atg7(Δβ cell)) mice and wild-type mice were administered vildagliptin for 12 weeks. Vildagliptin treatment improved glucose intolerance and hypoinsulinemia; however, it failed to suppress serum glucagon levels after glucose loading in the Atg7(Δβ cell) mice. Ex vivo glucose-induced glucagon suppression was also blunted in the islets from vildagliptin-treated Atg7(Δβ cell) mice. The α cell mass was not affected by β cell autophagy deficiency or vildagliptin. However, glucagon mRNA expression was significantly increased by vildagliptin in the autophagy-deficient islets, and was significantly reduced by vildagliptin in wild-type islets. Pancreatic glucagon contents were not in agreement with the changes in mRNA expression, suggesting a dysregulation in glucagon translation and secretion. In vitro studies revealed that glucose-stimulated cAMP production was impaired in the autophagy-deficient islets exposed to exendin-4. Taken together, the results suggest that the constitutive autophagy in β cells could regulate incretin-induced glucagon expression and release in α cells, and that cAMP may play a role in this process. PMID:26744903

  19. Autophagy deficiency in β cells blunts incretin-induced suppression of glucagon release from α cells

    PubMed Central

    Kim, Min Joo; Choi, Ok Kyong; Chae, Kyung Sil; Lee, Hakmo; Chung, Sung Soo; Ham, Dong-Sik; Kim, Ji-Won; Yoon, Kun-Ho; Park, Kyong Soo; Jung, Hye Seung

    2015-01-01

    Incretin-based therapy such as GLP-1 receptor agonists and DPP-4 inhibitors for type 2 diabetes mellitus is characterized by glucose-dependent insulin secretion and glucose-inhibited glucagon secretion. Recently, autophagy deficiency in islet β cells has been shown to contribute to the pathogenesis of type 2 diabetes mellitus however, with the role of incretin has not been established. To evaluate the role of autophagy in incretin effects, 8-week-old male β cell-specific Atg7 knockout (Atg7Δβ cell) mice and wild-type mice were administered vildagliptin for 12 weeks. Vildagliptin treatment improved glucose intolerance and hypoinsulinemia; however, it failed to suppress serum glucagon levels after glucose loading in the Atg7Δβ cell mice. Ex vivo glucose-induced glucagon suppression was also blunted in the islets from vildagliptin-treated Atg7Δβ cell mice. The α cell mass was not affected by β cell autophagy deficiency or vildagliptin. However, glucagon mRNA expression was significantly increased by vildagliptin in the autophagy-deficient islets, and was significantly reduced by vildagliptin in wild-type islets. Pancreatic glucagon contents were not in agreement with the changes in mRNA expression, suggesting a dysregulation in glucagon translation and secretion. In vitro studies revealed that glucose-stimulated cAMP production was impaired in the autophagy-deficient islets exposed to exendin-4. Taken together, the results suggest that the constitutive autophagy in β cells could regulate incretin-induced glucagon expression and release in α cells, and that cAMP may play a role in this process. PMID:26744903

  20. Vasodilator-Stimulated Phosphoprotein Deficiency Potentiates PAR-1-induced Increase in Endothelial Permeability in Mouse Lungs

    PubMed Central

    Profirovic, Jasmina; Han, Jingyan; Andreeva, Alexandra V.; Neamu, Radu F.; Pavlovic, Sasha; Vogel, Stephen M.; Walter, Ulrich; Voyno-Yasenetskaya, Tatyana A.

    2010-01-01

    Vasodilator-stimulated phosphoprotein (VASP) is implicated in the protection of the endothelial barrier in vitro and in vivo. VASP function in thrombin signaling in the endothelial cells (ECs) is not known. For the first time we studied the effects of VASP deficiency on EC permeability and pulmonary vascular permeability in response to thrombin receptor stimulation. We provided the evidence that VASP deficiency potentiates the increase in endothelial permeability induced by activation of thrombin receptor in cultured human umbilical vein endothelial cells (HUVECs) and isolated mouse lungs. Using transendothelial resistance measurement, we showed that siRNA-mediated VASP downregulation in HUVECs leads to a potentiation of thrombin- and protease-activated receptor 1 (PAR-1) agonist-induced increase in endothelial permeability. Compared to control cells, VASP-deficient HUVECs had delayed endothelial junctional reassembly and abrogated VE-cadherin cytoskeletal anchoring in the recovery phase after thrombin stimulation, as demonstrated by immunofluorescence studies and cell fractionation analysis, respectively. Measurement of the capillary filtration coefficient in isolated mouse lungs demonstrated that VASP−/− mice have increased microvascular permeability in response to infusion with PAR-1 agonist compared to wild type mice. Lack of VASP led to decreased Rac1 activation both in VASP-deficient HUVECs after thrombin stimulation and VASP−/− mouse lungs after PAR-1 agonist infusion, indicating that VASP effects on thrombin signaling may correlated with changes in Rac1 activity. This study demonstrates that VASP may play critical and complex role in the regulation of thrombin-dependent disruption of the endothelial barrier function. PMID:20945373

  1. Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced Parkinsonism.

    PubMed

    Qin, Xiaocui; Wu, Qiaoqi; Lin, Lifang; Sun, Aimin; Liu, Shuhu; Li, Xiaowen; Cao, Xiong; Gao, Tianming; Luo, Pengcheng; Zhu, Xinhong; Wang, Xuemin

    2015-08-01

    Soluble epoxide hydrolase (sEH) inhibition has been demonstrated to have beneficial effects on various diseases, such as hypertension, diabetes, and brain ischemia. However, whether sEH inhibition has therapeutic potential in Parkinson's disease is still unknown. In this paper, we found that sEH expression is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-treated mice, and sEH deficiency and inhibition significantly attenuated tyrosine hydroxylase (TH)-positive cell loss and improved rotarod performance. The substrate of sEH, 14,15-epoxyeicosatrienoic acid (14,15-EET), protected TH-positive cells and alleviated the rotarod performance deficits of wild-type mice but not sEH-knockout mice. Moreover, the 14,15-EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) abolished the neuronal protective effects of sEH deficiency. In primary cultured cortical neurons, MPP(+) induced significant Akt inactivation in neurons from sEH wild-type mice, and this effect was not observed in neurons from knockout mice. Our data indicate that sEH deficiency and inhibition increased 14,15-EET in MPTP-treated mice, which activated the Akt-mediated protection of TH-positive neurons and behavioral functioning. We also found that sEH deficiency attenuated TH-positive cell loss in a paraquat-induced mouse model of Parkinson's. Our data suggest that sEH inhibition might be a powerful tool to protect dopaminergic neurons in Parkinson's disease. PMID:25128026

  2. [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

  3. 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.

  4. Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model

    PubMed Central

    Darweesh, Amal Q; Fatani, Amal J

    2010-01-01

    In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine

  5. Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model.

    PubMed

    Sayed-Ahmed, Mohamed M; Darweesh, Amal Q; Fatani, Amal J

    2010-01-01

    In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4(th), 5(th) and 6(th) groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine

  6. 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

  7. 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

  8. Iodine content in bread, milk and the retention of inherent iodine in commonly used Indian recipes.

    PubMed

    Longvah, T; Toteja, G S; Upadhyay, A

    2013-01-15

    Iodine deficiency disorders (IDD) is still a major public health problem and iodized salt remains the most effective means to control IDD in India. Few reports indicate that vegans have inadequate iodine intake while at the same time concerns are being raised on the implementation of universal salt iodization in the country. Therefore, we investigated the iodine content in bread, milk and commonly used Indian recipes prepared without iodized salt and the retention of inherent iodine therein. Results showed considerable iodine content in bread (25 μg/100g) and milk (303 μg/L) as a positive fallout of universal salt iodization. Iodine content in 38 vegetarian recipes prepared without iodized salt was very low (2.9 ± 2.4 μg/100g). Retention of inherent iodine (65.6 ± 15.4%) and iodine from iodized salt (76.7 ± 10.3%) in the same recipes was comparable. Thus, universal salt iodization programme remains the single most important source of dietary iodine for the Indian population. PMID:23122074

  9. Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB₁ receptors: implications for schizophrenia.

    PubMed

    Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

    2013-08-01

    The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB₁-dependent manner, whereas pharmacological blockade of CB₁ receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB₁ receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB₁-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB₁ receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

  10. 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

  11. Generation of Glycosylphosphatidylinositol Anchor Protein-Deficient Blood Cells From Human Induced Pluripotent Stem Cells

    PubMed Central

    Yuan, Xuan; Braunstein, Evan M.; Ye, Zhaohui; Liu, Cyndi F.; Chen, Guibin; Zou, Jizhong; Cheng, Linzhao

    2013-01-01

    PIG-A is an X-linked gene required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIG-A mutant cells have a deficiency or absence of all GPI-anchored proteins (GPI-APs). Acquired mutations in hematopoietic stem cells result in the disease paroxysmal nocturnal hemoglobinuria, and hypomorphic germline PIG-A mutations lead to severe developmental abnormalities, seizures, and early death. Human induced pluripotent stem cells (iPSCs) can differentiate into cell types derived from all three germ layers, providing a novel developmental system for modeling human diseases. Using PIG-A gene targeting and an inducible PIG-A expression system, we have established, for the first time, a conditional PIG-A knockout model in human iPSCs that allows for the production of GPI-AP-deficient blood cells. PIG-A-null iPSCs were unable to generate hematopoietic cells or any cells expressing the CD34 marker and were defective in generating mesodermal cells expressing KDR/VEGFR2 (kinase insert domain receptor) and CD56 markers. In addition, PIG-A-null iPSCs had a block in embryonic development prior to mesoderm differentiation that appears to be due to defective signaling through bone morphogenetic protein 4. However, early inducible PIG-A transgene expression allowed for the generation of GPI-AP-deficient blood cells. This conditional PIG-A knockout model should be a valuable tool for studying the importance of GPI-APs in hematopoiesis and human development. PMID:24113066

  12. Vitamin D deficiency and exercise-induced laryngospasm in young competitive rowers.

    PubMed

    Heffler, Enrico; Bonini, Matteo; Brussino, Luisa; Solidoro, Paolo; Guida, Giuseppe; Boita, Monica; Nicolosi, Giuliana; Bucca, Caterina

    2016-07-01

    Exercise-induced dyspnea is common among adolescents and young adults and often originates from exercise-induced bronchoconstriction (EIB). Sometimes, dyspnea corresponds to exercise-induced laryngospasm (EILO), which is a paradoxical decrease in supraglottic/glottic area. Vitamin D deficiency, which occurs frequently at northern latitudes, might favor laryngospasm by impairing calcium transport and slowing striate muscle relaxation. The aim of this study was to evaluate whether vitamin D status has an influence on bronchial and laryngeal responses to exercise in young, healthy athletes. EIB and EILO were investigated during winter in 37 healthy competitive rowers (24 males; age range 13-25 years), using the eucapnic voluntary hyperventilation test (EVH). EIB was diagnosed when forced expiratory volume in the first second decreased by 10%, EILO when maximum mid-inspiratory flow (MIF50) decreased by 20%. Most athletes (86.5%) had vitamin D deficiency (below 30 ng/mL), 29 mild-moderate (78.4%) and 3 severe (8.1%). EVH showed EIB in 10 subjects (27%), EILO in 16 (43.2%), and combined EIB and EILO in 6 (16.2%). Athletes with EILO had lower vitamin D (19.1 ng/mL vs. 27.0 ng/mL, p < 0.001) and higher parathyroid hormone (30.5 pg/mL vs. 19.2 pg/mL, p = 0.006) levels. The degree of laryngoconstriction (post-EVH MIF50 as a percentage of pre-EVH MIF50) was related directly with vitamin D levels (r = 0.51; p = 0.001) and inversely with parathyroid hormone levels (r = -0.53; p = 0.001). We conclude that vitamin D deficiency is common during winter in young athletes living above the 40th parallel north and favors laryngospasm during exercise, probably by disturbing calcium homeostasis. This effect may negatively influence athletic performance. PMID:27218140

  13. Tetrahydrobiopterin Deficiency and Nitric Oxide Synthase Uncoupling Contribute to Atherosclerosis Induced by Disturbed Flow

    PubMed Central

    Li, Li; Chen, Wei; Rezvan, Amir; Jo, Hanjoong; Harrison, David G.

    2011-01-01

    Objective Tetrahydrobiopterin (BH4) is a critical cofactor for Nitric Oxide (NO) synthesis by NO synthase (NOS). Recently, we demonstrated that disturbed flow produced by partial carotid ligation decreases BH4 levels in vivo. We therefore aimed to determine whether atherosclerosis induced by disturbed flow is due to BH4 deficiency and NOS uncoupling and whether increasing BH4 would prevent endothelial dysfunction, plaque inflammation and atherosclerosis. Methods and Results We produced a region of disturbed flow in ApoE−/− mice using partial carotid ligation and fed these animals a high-fat diet. This caused eNOS uncoupling as characterized by increased vascular superoxide production, altered vascular reactivity and a change in eNOS migration on low-temperature gel. These perturbations were accompanied by severe atherosclerosis, infiltration of T cells and macrophages, and an increase in cytokine production. Treatment with BH4 recoupled NOS, decreased superoxide production, imporoved endothelium-dependent vasodilatation and virtually eliminated atherosclerosis. BH4 treatment also markedly reduced vascular inflammation and improved the cytokine milieu induced by disturbed flow. Conclusions Our results highlight a key role of BH4 deficiency and NOS uncoupling in atherosclerosis induced by disturbed flow, and provide insight into the effect of modulating vascular BH4 levels on atherosclerosis and inflammation at these sites of the circulation. PMID:21512164

  14. Selenium Deficiency-Induced Inflammation and Increased Expression of Regulating Inflammatory Cytokines in the Chicken Gastrointestinal Tract.

    PubMed

    Gao, Xuejiao; Zhang, Ziwei; Xing, Houjuan; Yu, Jiao; Zhang, Naisheng; Xu, Shiwen

    2016-09-01

    Selenium (Se), a nutritionally essential trace element, plays an important role in various aspects of health for a wide range of species, including birds. Se deficiency inhibits the growth of immune organs and decreases immune function, leading to many inflammatory diseases. The present study determined the effects and mechanism of dietary Se deficiency on gastrointestinal tract tissue inflammation. The histopathological changes showed that Se deficiency induced inflammatory lesions in the gastrointestinal tract tissues (glandular stomach, gizzard, duodenum, small intestine, and rectum). The expression levels of PTGE (prostagland E synthase), COX-2 (cyclooxygenase-2), TNF-α (tumor necrosis factor α), and NF-κB (nuclear transfer factor κB) in the gastrointestinal tract tissues (glandular stomach, gizzard, duodenum, small intestine, and rectum) were determined by qPCR on days 15, 25, 35, 45, and 55, respectively. The results showed that Se deficiency induced high expression levels of PTGE, COX-2, TNF-α, and NF-κB in the gastrointestinal tract tissues. The effects were more obvious in the duodenum and small intestine than those in the glandular stomach, gizzard, and rectum. In addition, the expression levels of these proteins in the gastrointestinal tract tissue increased in a time-dependent manner with Se deficiency feeding time. Furthermore, Se deficiency induced the production of pro-inflammatory factors, thus aggravating inflammatory lesions in the gastrointestinal tract. The effect of Se deficiency on inflammation and other gastrointestinal tract diseases should be further studied. PMID:26899319

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

    PubMed Central

    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.

    2012-01-01

    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. PMID:23041626

  16. The proinflammatory phenotype of PECAM-1-deficient mice results in atherogenic diet-induced steatohepatitis.

    PubMed

    Goel, Reema; Boylan, Brian; Gruman, Lynn; Newman, Peter J; North, Paula E; Newman, Debra K

    2007-12-01

    The severity of nonalcoholic steatohepatitis (NASH) is determined by environmental and genetic factors, the latter of which are incompletely characterized. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa transmembrane glycoprotein expressed on blood and vascular cells. In the present study, we provide data for the novel finding that genetic deficiency of PECAM-1 potentiates the development and progression of NASH. We found that the rate of development and severity of diet-induced NASH are markedly enhanced in PECAM-1-deficient [knockout (KO)] mice relative to wild-type (WT) mice, as measured by histological and biochemical evaluation. Livers from KO mice exhibited typical histological features of NASH, including macrovesicular fat accumulation, hepatocyte injury with infiltration of inflammatory cells, fibrosis, and heightened oxidative stress. Alanine aminotransferase, a marker for liver injury, was also significantly higher in KO compared with WT mice. Consistent with a role for PECAM-1 as a suppressor of proinflammatory cytokines, plasma levels of inflammatory cytokines, including TNF-alpha and monocyte chemoattractant protein-1 (MCP-1), were also significantly higher in KO compared with WT mice. These findings are the first to show that the PECAM-1-deficient mouse develops progressive nonalcoholic fatty liver disease (NAFLD), supporting a role for PECAM-1 as a negative regulator of NAFLD progression. Future examination of recently identified PECAM-1 allelic isoforms in humans as potential risk factors for developing NASH may be warranted. PMID:17932230

  17. 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

  18. GRK5 deficiency leads to susceptibility to intermittent hypoxia-induced cognitive impairment.

    PubMed

    Singh, Prabhakar; Peng, Wei; Zhang, Qiang; Ding, XueFeng; Suo, William Z

    2016-04-01

    Obstructive sleep apnea (OSA) leads to cognitive impairment in about 25% patients, though it remains elusive what makes one more susceptible than the other to be cognitively impaired. G protein-coupled receptor kinase-5 (GRK5) deficiency is recently found to render subjects more susceptible to cognitive impairment triggered by over-expression of Swedish mutant ß-amyloid precursor protein. This study is to determine whether GRK5 deficiency also renders subjects more susceptible to the OSA-triggered cognitive impairment. Both wild type (WT) and GRK5 knockout (KO) mice were placed in conditions absence and presence of intermittent hypoxia (IH) with 8%/21% O2 90-s cycle for 8h a day for a month, and then followed by behavioral assessments with battery of tasks. We found that the selected IH condition only induced marginally abnormal behavior (slightly elevated anxiety with most others unchanged) in the WT mice but it caused significantly more behavioral deficits in the KO mice, ranging from elevated anxiety, impaired balancing coordination, and impaired short-term spatial memory. These results suggest that GRK5 deficiency indeed makes the mice more susceptible to wide range of behavioral impairments, including cognitive impairments. PMID:26778781

  19. Use of iodine for water disinfection: iodine toxicity and maximum recommended dose.

    PubMed Central

    Backer, H; Hollowell, J

    2000-01-01

    Iodine is an effective, simple, and cost-efficient means of water disinfection for people who vacation, travel, or work in areas where municipal water treatment is not reliable. However, there is considerable controversy about the maximum safe iodine dose and duration of use when iodine is ingested in excess of the recommended daily dietary amount. The major health effect of concern with excess iodine ingestion is thyroid disorders, primarily hypothyroidism with or without iodine-induced goiter. A review of the human trials on the safety of iodine ingestion indicates that neither the maximum recommended dietary dose (2 mg/day) nor the maximum recommended duration of use (3 weeks) has a firm basis. Rather than a clear threshold response level or a linear and temporal dose-response relationship between iodine intake and thyroid function, there appears to be marked individual sensitivity, often resulting from unmasking of underlying thyroid disease. The use of iodine for water disinfection requires a risk-benefit decision based on iodine's benefit as a disinfectant and the changes it induces in thyroid physiology. By using appropriate disinfection techniques and monitoring thyroid function, most people can use iodine for water treatment over a prolonged period of time. PMID:10964787

  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. PMID:25866202

  1. 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

  2. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline

    PubMed Central

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-01-01

    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. PMID:25866202

  3. 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

  4. 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

  5. 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

  6. Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

    PubMed Central

    Santana, Alfredo; Medina, Carlos; Paz-Cabrera, Maria Cristina; Díaz-Gonzalez, Federico; Farré, Esther; Salas, Antonio; Radomski, Marek W; Quintero, Enrique

    2006-01-01

    AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice. METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelial injury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation. PMID:17072979

  7. 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. PMID:25599449

  8. Persistence of LPS-induced lung inflammation in surfactant protein-C-deficient mice.

    PubMed

    Glasser, Stephan W; Maxfield, Melissa D; Ruetschilling, Teah L; Akinbi, Henry T; Baatz, John E; Kitzmiller, Joseph A; Page, Kristen; Xu, Yan; Bao, Erik L; Korfhagen, Thomas R

    2013-11-01

    Pulmonary surfactant protein-C (SP-C) gene-targeted mice (Sftpc(-/-)) develop progressive lung inflammation and remodeling. We hypothesized that SP-C deficiency reduces the ability to suppress repetitive inflammatory injury. Sftpc(+/+) and Sftpc(-/-) mice given three doses of bacterial LPS developed airway and airspace inflammation, which was more intense in the Sftpc(-/-) mice at 3 and 5 days after the final dose. Compared with Sftpc(+/+)mice, inflammatory injury persisted in the lungs of Sftpc(-/-) mice 30 days after the final LPS challenge. Sftpc(-/-) mice showed LPS-induced airway goblet cell hyperplasia with increased detection of Sam pointed Ets domain and FoxA3 transcription factors. Sftpc(-/-) type II alveolar epithelial cells had increased cytokine expression after LPS exposure relative to Sftpc(+/+) cells, indicating that type II cell dysfunction contributes to inflammatory sensitivity. Microarray analyses of isolated type II cells identified a pattern of enhanced expression of inflammatory genes consistent with an intrinsic low-level inflammation resulting from SP-C deficiency. SP-C-containing clinical surfactant extract (Survanta) or SP-C/phospholipid vesicles blocked LPS signaling through the LPS receptor (Toll-like receptor [TLR] 4/CD14/MD2) in human embryonic kidney 293T cells, indicating that SP-C blocks LPS-induced cytokine production by a TLR4-dependent mechanism. Phospholipid vesicles alone did not modify the TLR4 response. In vivo deficiency of SP-C leads to inflammation, increased cytokine production by type II cells, and persistent inflammation after repetitive LPS stimulation. PMID:23795648

  9. Growth hormone secretagogue receptor deficiency in mice protects against obesity‐induced hypertension

    PubMed Central

    Harris, Louise E.; Morgan, David G.; Balthasar, Nina

    2014-01-01

    Abstract Growth hormone secretagogue receptor (GHS‐R) signaling has been associated with growth hormone release, increases in food intake and pleiotropic cardiovascular effects. Recent data demonstrated that acute GHS‐R antagonism leads to increases in mean arterial pressure mediated by the sympathetic nervous system in rats; a highly undesirable effect if GHS‐R antagonism was to be used as a therapeutic approach to reducing food intake in an already obese, hypertensive patient population. However, our data in conscious, freely moving GHS‐R deficient mice demonstrate that chronic absence of GHS‐R signaling is protective against obesity‐induced hypertension. GHS‐R deficiency leads to reduced systolic blood pressure variability (SBPV); in response to acute high‐fat diet (HFD)‐feeding, increases in the sympathetic control of SBPV are suppressed in GHS‐R KO mice. Our data further suggest that GHS‐R signaling dampens the immediate HFD‐mediated increase in spontaneous baroreflex sensitivity. In diet‐induced obesity, absence of GHS‐R signaling leads to reductions in obesity‐mediated hypertension and tachycardia. Collectively, our findings thus suggest that chronic blockade of GHS‐R signaling may not result in adverse cardiovascular effects in obesity. PMID:24760503

  10. High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

    PubMed

    Yang, Yang; Jing, Xiao-Peng; Zhang, Shou-Peng; Gu, Run-Xia; Tang, Fang-Xu; Wang, Xiu-Lian; Xiong, Yan; Qiu, Mei; Sun, Xu-Ying; Ke, Dan; Wang, Jian-Zhi; Liu, Rong

    2013-01-01

    Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit. PMID:23383172

  11. Paradoxical Relationship between Mn Superoxide Dismutase Deficiency and Radiation-Induced Cognitive Defects

    PubMed Central

    Corniola, Rikki; Zou, Yani; Leu, David; Fike, John R.; Huang, Ting-Ting

    2012-01-01

    Radiation therapy of the CNS, even at low doses, can lead to deficits in neurocognitive functions. Reduction in hippocampal neurogenesis is usually, but not always, associated with cognitive deficits resulting from radiation therapy. Generation of reactive oxygen species is considered the main cause of radiation-induced tissue injuries, and elevated levels of oxidative stress persist long after the initial cranial irradiation. Consequently, mutant mice with reduced levels of the mitochondrial antioxidant enzyme, Mn superoxide dismutase (MnSOD or Sod2), are expected to be more sensitive to radiation-induced changes in hippocampal neurogenesis and the related functions. In this study, we showed that MnSOD deficiency led to reduced generation of immature neurons in Sod2−/+ mice even though progenitor cell proliferation was not affected. Compared to irradiated Sod2+/+ mice, which showed cognitive defects and reduced differentiation of newborn cells towards the neuronal lineage, irradiated Sod2−/+ mice showed normal hippocampal-dependent cognitive functions and normal differentiation pattern for newborn neurons and astroglia. However, we also observed a disproportional decrease in newborn neurons in irradiated Sod2−/+ following behavioral studies, suggesting that MnSOD deficiency may render newborn neurons more sensitive to stress from behavioral trainings following cranial irradiation. A positive correlation between normal cognitive functions and normal dendritic spine densities in dentate granule cells was observed. The data suggest that maintenance of synaptic connections, via maintenance of dendritic spines, may be important for normal cognitive functions following cranial irradiation. PMID:23145165

  12. Defective development of pristane-oil-induced plasmacytomas in interleukin-6-deficient BALB/c mice.

    PubMed

    Lattanzio, G; Libert, C; Aquilina, M; Cappelletti, M; Ciliberto, G; Musiani, P; Poli, V

    1997-09-01

    Interleukin (IL)-6 is known to be an essential growth factor for myeloma cells, both in vitro and in vivo. In mice, IL-6 is required for development of B cell tumors upon infection with a retrovirus expressing the myc/raf oncogenes. In the present study, we used the pristane-oil-induced plasmacytoma model, which more closely mimics tumor transformation and progression in human multiple myeloma. Also using this system, we found that IL-6-deficient BALB/c mice are protected against tumor development. Although the pristane-induced inflammatory reaction was less pronounced in IL-6-deficient mice versus their wild-type littermates, both B cell differentiation and plasma cell formation took place, and even morphological evidence of plasma cell transformation was detected, albeit at a low frequency. However, in the absence of IL-6, there were never signs of uncontrolled proliferation of either normal B lymphocytes or tumor cells, suggesting that the role of IL-6 in murine plasmacytoma and possibly also in human multiple myeloma is to ensure abnormal survival and proliferation of previously transformed tumor cells and therefore tumor development and progression. PMID:9284817

  13. Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice

    PubMed Central

    Liu, Jian; Divoux, Adeline; Sun, Jiusong; Zhang, Jie; Clément, Karine; Glickman, Jonathan N.; Sukhova, Galina K.; Wolters, Paul J.; Du, Juan; Gorgun, Cem Z.; Doria, Alessandro; Libby, Peter; Blumberg, Richard S.; Kahn, Barbara B.; Hotamisligil, Gokhan S.; Shi, Guo-Ping

    2009-01-01

    Although mast cell functions classically relate to allergic responses1–3, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm, and cancer4–8. This study presents evidence that mast cells contribute importantly to diet-induced obesity and diabetes. White adipose tissues (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Genetically determined mast cell deficiency and pharmacological stabilization of mast cells in mice reduce body weight gain and levels of inflammatory cytokines, chemokines, and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer of cytokine-deficient mast cells established that these cells contribute to mice adipose tissue cysteine protease cathepsin expression, apoptosis, and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance by production of IL6 and IFN-γ. Mast cell stabilizing agents in clinical use reduced obesity and diabetes in mice, suggesting the potential of developing novel therapies for these common human metabolic disorders. PMID:19633655

  14. 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. PMID:26092248

  15. IFN-γ deficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine- and choline-deficient high-fat diet.

    PubMed

    Luo, Xiao-Yu; Takahara, Terumi; Kawai, Kengo; Fujino, Masayuki; Sugiyama, Toshiro; Tsuneyama, Koichi; Tsukada, Kazuhiro; Nakae, Susumu; Zhong, Liang; Li, Xiao-Kang

    2013-12-01

    Cytokines play important roles in all stages of steatohepatitis, including hepatocyte injury, the inflammatory response, and the altered function of sinusoidal cells. This study examined the involvement of a major inflammatory cytokine, interferon-γ (IFN-γ), in the progression of steatohepatitis. In a steatohepatitis model by feeding a methionine- and choline-deficient high-fat (MCDHF) diet to both wild-type and IFN-γ-deficient mice, the liver histology, expression of genes encoding inflammatory cytokines, and fibrosis-related markers were examined. To analyze the effects of IFN-γ on Kupffer cells in vitro, we examined the tumor necrosis factor-α (TNF-α) production by a mouse macrophage cell line. Forty two days of MCDHF diet resulted in weight loss, elevated aminotransferases, liver steatosis, and inflammation in wild-type mice. However, the IFN-γ-deficient mice exhibited less extensive changes. RT-PCR revealed that the expression of tumor necrosis factor-α (TNF-α), transforming growth factor-β, inducible nitric oxide synthase, interleukin-4 and osteopontin were increased in wild-type mice, although they were suppressed in IFN-γ-deficient mice. Seventy days of MCDHF diet induced much more liver fibrosis in wild-type mice than in IFN-γ-deficient mice. The expression levels of fibrosis-related genes, α-smooth muscle actin, type I collagen, tissue inhibitor of matrix metalloproteinase-1, and matrix metalloproteinase-2, were dramatically increased in wild-type mice, whereas they were significantly suppressed in IFN-γ-deficient mice. Moreover, in vitro experiments showed that, when RAW 264.7 macrophages were treated with IFN-γ, they produced TNF-α in a dose-dependent manner. The present study showed that IFN-γ deficiency might inhibit the inflammatory response of macrophages cells and subsequently suppress stellate cell activation and liver fibrosis. These findings highlight the critical role of IFN-γ in the progression of steatohepatitis. PMID

  16. 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

  17. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice

    PubMed Central

    2011-01-01

    Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin) induced cardiac toxicity. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p.), left ventricular pressure volume loops were measured in HeN compotent (TLR4+/+) and HeJ mutant (TLR4-/-) treated with trastuzumab and control mice. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs) for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α), Western immunoblotting assay for ICAM-1, and used troponin I for cardiac injury marker. Results Trastuzumab injection resulted in an impairment of left ventricular function in TLR-4 competent (HeN), in contrast TLR4-/- trastuzumab mice showed improved left ventricular function EF%, CO; p < 0.05, attenuation of mononuclear cell infiltration in TLR4 -/-; p < 0.05 vs.TLR-4 competent (HeN), reduced level of cytokines TNF-α, MCP-1 and ICAM-1 expression in TLR4-/-, marked reduction of myocardial troponin-I levels in TLR4-deficient mice. Data are presented as means ± SE; n = 8 in each group p < 0.05 vs.TLR-4 competent (HeN). Conclusions Treatment with trastuzumab induces an inflammatory response that contributes to myocardial tissue TLR4 mediates chemokine expression (TNF-α, MCP-1and ICAM-1), so in experimental animals TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in trastuzumab induced cardiomyopathy. PMID:21999911

  18. 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

  19. 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. PMID:26754788

  20. Collagenase-3 (MMP-13) deficiency protects C57BL/6 mice from antibody-induced arthritis

    PubMed Central

    2013-01-01

    Introduction Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis. Methods For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13–/–) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacrificed every second day for histological examination of the ankle joints. Ankle sections were evaluated histologically for infiltration of inflammatory cells, pannus tissue formation and bone/cartilage destruction. Semi-quantitative PCR was used to determine MMP-13 expression levels in ankle joints of untreated and K/BxN serum-injected mice. Results This study shows that MMP-13 is a regulator of inflammation. We observed increased expression of MMP-13 in ankle joints of WT mice during K/BxN serum-induced arthritis and both K/BxN serum-treated WT and MMP-13–/– mice developed progressive arthritis with a similar onset. However, MMP-13–/– mice showed significantly reduced disease over the whole arthritic period. Ankle joints of WT mice showed severe joint destruction with extensive inflammation and erosion of cartilage and bone. In contrast, MMP-13–/– mice displayed significantly decreased severity of arthritis (50% to 60%) as analyzed by clinical and histological scoring methods. Conclusions MMP-13 deficiency acts to suppress the local inflammatory responses. Therefore, MMP-13 has a role in the pathogenesis of arthritis, suggesting MMP-13 is a potential therapeutic target. PMID:24369907

  1. Resveratrol prevents rapamycin-induced upregulation of autophagy and selectively induces apoptosis in TSC2-deficient cells

    PubMed Central

    Alayev, Anya; Sun, Yang; Snyder, Rose B; Berger, Sara Malka; Yu, Jane J; Holz, Marina K

    2014-01-01

    The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is hyperactivated in a variety of cancers and disorders, including lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC), which are characterized by mutations in tumor suppressors TSC1 or TSC2. The concern with the use of mTORC1 inhibitors, such as rapamycin or its analogs (rapalogs), is that they cause upregulation of autophagy and suppress the negative feedback loop to Akt, which promotes cell survival, causing the therapy to be only partially effective, and relapse occurs upon cessation of treatment. In this study, we investigate the use of rapamycin in combination with resveratrol, a naturally occurring polyphenol, in TSC2-deficient cells. We tested whether such combination would prevent rapamycin-induced upregulation of autophagy and shift the cell fate toward apoptosis. We found that this combination treatment blocked rapamycin-induced upregulation of autophagy and restored inhibition of Akt. Interestingly, the combination of rapamycin and resveratrol selectively promoted apoptosis of TSC2-deficient cells. Thus, the addition of resveratrol to rapamycin treatment may be a promising option for selective and targeted therapy for diseases with TSC loss and mTORC1 hyperactivation. PMID:24304514

  2. 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

  3. 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.

  4. Endothelial cell tetrahydrobiopterin deficiency attenuates LPS-induced vascular dysfunction and hypotension☆

    PubMed Central

    Chuaiphichai, Surawee; Starr, Anna; Nandi, Manasi; Channon, Keith M.; McNeill, Eileen

    2016-01-01

    Overproduction of nitric oxide (NO) is thought to be a key mediator of the vascular dysfunction and severe hypotension in patients with endotoxaemia and septic shock. The contribution of NO produced directly in the vasculature by endothelial cells to the hypotension seen in these conditions, vs. the broader systemic increase in NO, is unclear. To determine the specific role of endothelium derived NO in lipopolysaccharide (LPS)-induced vascular dysfunction we administered LPS to mice deficient in endothelial cell tetrahydrobiopterin (BH4), the essential co-factor for NO production by NOS enzymes. Mice deficient in endothelial BH4 production, through loss of the essential biosynthesis enzyme Gch1 (Gch1fl/flTie2cre mice) received a 24 hour challenge with LPS or saline control. In vivo LPS treatment increased vascular GTP cyclohydrolase and BH4 levels in aortas, lungs and hearts, but this increase was significantly attenuated in Gch1fl/flTie2cre mice, which were also partially protected from the LPS-induced hypotension. In isometric tension studies, in vivo LPS treatment reduced the vasoconstriction response and impaired endothelium-dependent and independent vasodilatations in mesenteric arteries from wild-type mice, but not in Gch1fl/flTie2cre mesenteric arteries. Ex vivo LPS treatment decreased vasoconstriction response to phenylephrine in aortic rings from wild-type and not in Gch1fl/flTie2cre mice, even in the context of significant eNOS and iNOS upregulation. These data provide direct evidence that endothelial cell NO has a significant contribution to LPS-induced vascular dysfunction and hypotension and may provide a novel therapeutic target for the treatment of systemic inflammation and patients with septic shock. PMID:26276526

  5. 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

  6. 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.

  7. 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

  8. Vitamin D deficiency exacerbates atypical antipsychotic-induced metabolic side effects in rats: involvement of the INSIG/SREBP pathway.

    PubMed

    Dang, Ruili; Jiang, Pei; Cai, Hualin; Li, Huande; Guo, Ren; Wu, Yanqin; Zhang, Lihong; Zhu, Wenye; He, Xin; Liu, Yiping; Xu, Ping

    2015-08-01

    Metabolic syndrome is a major concern in psychotic patients receiving atypical antipsychotics. Recent evidence suggests that sterol regulatory element-binding proteins (SREBPs) and insulin-induced genes (INSIGs) are implicated in the antipsychotic-induced metabolic side-effects. Vitamin D (VD) deficiency, a highly prevalent phenomenon among patients with psychosis, might also predispose individuals to metabolic syndrome Considering that VD has modulating effects on the INSIG/SREBP pathway, it is possible that VD may have a role in the antipsychotic-induced metabolic disturbances involving its effects on the INSIG/SREBP system. Thus, the present study aimed to evaluate the effects of VD deficiency and VD supplementation on antipsychotic-induced metabolic changes in rats. After 4-week administration, clozapine (10mg/kg/d) and risperidone (1mg/kg/d) both caused glucose intolerance and insulin resistance in VD deficient rats, but not in rats with sufficient VD status. Antipsychotic treatments, especially clozapine, elevated serum lipid levels, which were most apparent in VD deficient rats, but alleviated in VD-supplemented rats. Additionally, antipsychotic treatments down-regulated INSIGs and up-regulated SREBPs expression in VD deficient rats, and these effects were attenuated when VD status was more sufficient. Collectively, this study disclose the novel findings that antipsychotic-induced metabolic disturbances is exacerbated by VD deficiency and can be alleviated by VD supplementation, providing new evidence for the promising role of VD in prevention and treatment of metabolic disorders caused by antipsychotic medications. Furthermore, our data also suggest the involvement of INSIG/SREBP pathway in the antipsychotic-induced hyperlipidemia and beneficial effects of VD on lipid profile. PMID:26003080

  9. Nox2 Deficiency Prevents Hypertension-Induced Vascular Dysfunction and Hypertrophy in Cerebral Arterioles

    PubMed Central

    Chan, Siu-Lung; Baumbach, Gary L.

    2013-01-01

    Oxidative stress is involved in many hypertension-related vascular diseases in the brain, including stroke and dementia. Thus, we examined the role of genetic deficiency of NADPH oxidase subunit Nox2 in the function and structure of cerebral arterioles during hypertension. Arterial pressure was increased in right-sided cerebral arterioles with transverse aortic banding for 4 weeks in 8-week-old wild-type (WT) and Nox2-deficient (-/y) mice. Mice were given NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) or vehicle to drink. We measured the reactivity in cerebral arterioles through open cranial window in anesthetized mice and wall cross-sectional area and superoxide levels ex vivo. Aortic constriction increased systolic and pulse pressures in right-sided carotid arteries in all groups of mice. Ethidium fluorescence showed increased superoxide in right-sided cerebral arterioles in WT, but not in Nox2-/y mice. Dilation to acetylcholine, but not sodium nitroprusside, was reduced, and cross-sectional areas were increased in the right-sided arterioles in WT, but were unchanged in Nox2-/y mice. L-NAME reduced dilation to acetylcholine but did not result in hypertrophy in right-sided arterioles of Nox2-/y  mice. In conclusion, hypertension-induced superoxide production derived from Nox2-containing NADPH oxidase promotes hypertrophy and causes endothelial dysfunction in cerebral arterioles, possibly involving interaction with nitric oxide. PMID:23573415

  10. 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

  11. Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes

    PubMed Central

    Khan, Mohammad Moshahid; Kempuraj, Duraisamy; Zaheer, Smita; Zaheer, Asgar

    2014-01-01

    Inflammation is closely intertwined with pathogenesis of Parkinson's disease (PD). Increasing evidence suggests that inhibition of glia-mediated inflammation might represent a promising therapeutic target for PD. Glia maturation factor (GMF), an inflammatory protein, predominantly localized in astrocytes is previously isolated, sequenced and cloned in our laboratory. In the present investigation, we demonstrate that GMF-deficiency in astrocytes upregulates the antioxidant status and limit the extent of lipid peroxidation and production of reactive oxygen species (ROS) along with diminished nuclear factor-κB-mediated inflammatory responses in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity. Primary astrocytes obtained from wild-type (Wt) and GMF-deficient (GMF-KO) mice were treated with 5, 10, and 20 μM MPP+ for 24, 48, and 72 h in vitro. Our results show decreased release of ROS and increased level of glutathione in astrocytes obtained from GMF-KO mice when compared to astrocytes derived from Wt mice following MPP+ treatment. Additionally, we found decreased activity of NF-κB, and reduced levels of proinflammatory tumor necrosis factor- α, interleukin-1β (IL-1β), IL-17, IL-33, and chemokine (C–C motif) ligand 2 (CCL2) in GMF-KO astrocytes when compared to Wt astrocytes. Our overall results suggest that GMF-KO astrocytes are significantly resistant to MPP+ toxicity when compared to Wt astrocytes. PMID:24430624

  12. Amelioration of Stroke-Induced Neurological Deficiency by Lyophilized Powder of Catapol and Puerarin

    PubMed Central

    Liu, Yang; Xue, Qiang; Li, Xu; Zhang, Jifen; Fu, Zhifeng; Feng, Binbin; Chen, Yi; Xu, Xiaoyu

    2014-01-01

    Catalpol and puerarin are active ingredients isolated from Rehmannia glutinosa Libosch and Radix Puerariae, respectively. They are popular in research for their poly-pharmacological effects. This research focused on effect of anti-stroke by lyophilized powder of catalpol and puerarin (C-P) and potential mechanisms. At the beginning of research, C-P was identified and analyzed by HPLC. Neurological function was evaluated by Longa score, neurological complex function score and beam balance score after permanent middle cerebral artery occlusion (PMCAO) in mice. Infarct volume and water content were evaluated after treatment of C-P. Anti-oxidative stress, anti-apoptosis, angiogenesis and neurogenesis were investigated by ELISA, WB and immunohistochemical stain respectively. With treatment of C-P, neurological deficiency of PMCAO mice was ameliorated. Morphologically, infarct volume and water content in ischemic hemisphere were significantly reduced by C-P. In vivo and in vitro, oxidative stress injury was extenuated by C-P. Meanwhile, Caspase-3 was down-regulated and Bxl-2 was up-regulated by C-P in vivo. In addition, C-P enhanced angiogenesis around the infarct of cortex and neurogenesis in the Hippocampal Dentate Gyrus (DG). Hence, C-P ameliorated stroke-induced neurological deficiency through its multiple neuroprotections. What's more, this article provides us a novel formula of active ingredients for stroke. PMID:24719562

  13. 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.

  14. Glia maturation factor deficiency suppresses 1-methyl-4-phenylpyridinium-induced oxidative stress in astrocytes.

    PubMed

    Khan, Mohammad Moshahid; Kempuraj, Duraisamy; Zaheer, Smita; Zaheer, Asgar

    2014-08-01

    Inflammation is closely intertwined with pathogenesis of Parkinson's disease (PD). Increasing evidence suggests that inhibition of glia-mediated inflammation might represent a promising therapeutic target for PD. Glia maturation factor (GMF), an inflammatory protein, predominantly localized in astrocytes is previously isolated, sequenced and cloned in our laboratory. In the present investigation, we demonstrate that GMF-deficiency in astrocytes upregulates the antioxidant status and limit the extent of lipid peroxidation and production of reactive oxygen species (ROS) along with diminished nuclear factor-κB-mediated inflammatory responses in 1-methyl-4-phenylpyridinium (MPP(+))-induced toxicity. Primary astrocytes obtained from wild-type (Wt) and GMF-deficient (GMF-KO) mice were treated with 5, 10, and 20 μM MPP(+) for 24, 48, and 72 h in vitro. Our results show decreased release of ROS and increased level of glutathione in astrocytes obtained from GMF-KO mice when compared to astrocytes derived from Wt mice following MPP(+) treatment. Additionally, we found decreased activity of NF-κB, and reduced levels of proinflammatory tumor necrosis factor- α, interleukin-1β (IL-1β), IL-17, IL-33, and chemokine (C-C motif) ligand 2 (CCL2) in GMF-KO astrocytes when compared to Wt astrocytes. Our overall results suggest that GMF-KO astrocytes are significantly resistant to MPP(+) toxicity when compared to Wt astrocytes. PMID:24430624

  15. Physiological responses of Tunisian grapevine varieties to bicarbonate-induced iron deficiency.

    PubMed

    Ksouri, Riadh; Gharsalli, Mohamed; Lachaal, Mokhtar

    2005-03-01

    Plants are frequently submitted to iron deficiency when growing on calcareous soils, which contain high concentrations of bicarbonate. The purpose of this study was to investigate the variability of physiological responses of Tunisian grapevine varieties to bicarbonate-induced iron chlorosis. Vine woodcuttings of seven autochthonous Tunisian varieties (Khamri, Mahdaoui, Blan3, Saouadi, Arich Dressé, Beldi and Balta4), two rootstocks (140Ru and S.O.4), and an introduced table variety (Cardinal) were cultivated on inert sand for 2 months using a complete nutrient solution (20 microM Fe) that was either well supplied or not supplied with 10 mM HCO3-. Young leaves of plants cultivated on bicarbonate-enriched medium showed characteristic symptoms of iron chlorosis, although the intensity of the symptoms depended on the variety and the rootstock. Chlorosis score confirmed these observations since the most sensitive varieties showed the highest values. This variability in tolerance to iron deficiency was also displayed when analysing the physiological parameters (shoot length, plant dry weight, and chlorophyll concentration) and the iron contents in the 4th leaf. Analysis of morphological and physiological parameters showed three behaviour groups. The first one corresponded to tolerant varieties (Khamri, Mahdaoui, and the root-stock: 140Ru), the second included moderately tolerant vines (Saouadi, Arich Dressé, Blanc3, and the rootstock: S.O.4) and the third represented the sensitive ones (Balta4, Beldi, and Cardinal). PMID:15832686

  16. Rapamycin Regulates Bleomycin-Induced Lung Damage in SP-C-Deficient Mice.

    PubMed

    Madala, Satish K; Maxfield, Melissa D; Davidson, Cynthia R; Schmidt, Stephanie M; Garry, Daniel; Ikegami, Machiko; Hardie, William D; Glasser, Stephan W

    2011-01-01

    Injury to the distal respiratory epithelium has been implicated as an underlying cause of idiopathic lung diseases. Mutations that result in SP-C deficiencies are linked to a small subset of spontaneous and familial cases of interstitial lung disease (ILD) and interstitial pulmonary fibrosis (IPF). Gene-targeted mice that lack SP-C (Sftpc(-/-)) develop an irregular ILD-like disease with age and are a model of the human SP-C related disease. In the current study, we investigated whether rapamycin could ameliorate bleomycin-induced fibrosis in the lungs of Sftpc(-/-) mice. Sftpc(+/+) and -/- mice were exposed to bleomycin with either preventative administration of rapamycin or therapeutic administration beginning eight days after the bleomycin injury. Rapamycin-treatment increased weight loss and decreased survival of bleomycin-treated Sftpc(+/+) and Sftpc(-/-) mice. Rapamycin did not reduce the fibrotic disease in the prophylactic or rescue experiments of either genotype of mice. Further, rapamycin treatment augmented airway resistance and reduced lung compliance of bleomycin-treated Sftpc(-/-) mice. Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-γ. These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD/IPF. PMID:21660239

  17. 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. PMID:26336925

  18. Low temperature synthesis of iodine-doped TiO 2 nanocrystallites with enhanced visible-induced photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Ma, Yi; Fu, Ji-Wen; Tao, Xia; Li, Xin; Chen, Jian-Feng

    2011-03-01

    Iodine-doped TiO 2 nanocrystallites (denoted as I-TNCs) were prepared via a newly developed triblock copolymer-mediated sol-gel method at a temperature of 393 K. I-doping, crystallization and the formation of porous structure have been simultaneously achieved. The obtained particles were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and UV-vis spectrophotometer. The results indicated that the as-prepared I-TNCs possessed a diameter of ca. 5 nm with anatase crystalline structure and a specific surface area of over 200 m 2 g -1. The presence of iodine expanded the photoresponse in visible light range, and led to enrich in surface hydroxyl group on the TiO 2 surface. Compared with the commercial photocatalyst P25, the I-TNCs significantly enhanced the photocatalytic efficiency in the degradation of rhodamine B and 2,4-dichlorophenol, and the I-TNCs with 2.5 mol% doping ratio exhibited the best photocatalytic activity.

  19. Rotation induced octupole correlations in the neutron-deficient 109Te nucleus

    NASA Astrophysics Data System (ADS)

    de Angelis, G.; Fahlander, C.; Gadea, A.; Farnea, E.; Bazzacco, D.; Belcari, N.; Blasi, N.; Bizzeti, P. G.; Bizzeti-Sona, A.; de Acuña, D.; de Poli, M.; Grawe, H.; Johnson, A.; Lo Bianco, G.; Lunardi, S.; Napoli, D. R.; Nyberg, J.; Pavan, P.; Persson, J.; Rossi Alvarez, C.; Rudolph, D.; Schubart, R.; Spolaore, P.; Wyss, R.; Xu, F.

    1998-10-01

    High spin states in the neutron deficient nucleus 109Te have been populated with the 58Ni+54Fe reaction at 220 MeV and investigated through γ-spectroscopy methods at the GASP spectrometer making use of reaction channel selection with the ISIS Si-ball. The level scheme has been extended up to an excitation energy of ~12.1 MeV. The spins and parities of the observed levels are assigned tentatively supporting the identification of two bands of opposite parity connected by strong dipole transitions inferred to be of E1 character. Octupole correlations in 109Te induced by rotation are suggested as the cause of this effect.

  20. Induced Structural Disorder as a Molecular Mechanism for Enzyme Dysfunction in Phosphoglucomutase 1 Deficiency.

    PubMed

    Stiers, Kyle M; Kain, Bailee N; Graham, Abigail C; Beamer, Lesa J

    2016-04-24

    Human phosphoglucomutase 1 (PGM1) plays a central role in cellular glucose homeostasis, mediating the switch between glycolysis and gluconeogenesis through the conversion of glucose 1-phosphate and glucose 6-phosphate. Recent clinical studies have identified mutations in this enzyme as the cause of PGM1 deficiency, an inborn error of metabolism classified as both a glycogen storage disease and a congenital disorder of glycosylation. Reported here are the first crystal structures of two disease-related missense variants of PGM1, along with the structure of the wild-type enzyme. Two independent glycine-to-arginine substitutions (G121R and G291R), both affecting key active site loops of PGM1, are found to induce regions of structural disorder, as evidenced by a nearly complete loss of electron density for as many as 23 aa. The disordered regions are not contiguous in sequence to the site of mutation, and even cross domain boundaries. Other structural rearrangements include changes in the conformations of loops and side chains, some of which occur nearly 20 Å away from the site of mutation. The induced structural disorder is correlated with increased sensitivity to proteolysis and lower-resolution diffraction, particularly for the G291R variant. Examination of the multi-domain effects of these G➔R mutations establishes a correlation between interdomain interfaces of the enzyme and missense variants of PGM1 associated with disease. These crystal structures provide the first insights into the structural basis of enzyme dysfunction in PGM1 deficiency and highlight a growing role for biophysical characterization of proteins in the field of precision medicine. PMID:26972339

  1. Relaxin deficiency attenuates pregnancy-induced adaptation of the mesenteric artery to angiotensin II in mice.

    PubMed

    Marshall, Sarah A; Leo, Chen Huei; Senadheera, Sevvandi N; Girling, Jane E; Tare, Marianne; Parry, Laura J

    2016-05-01

    Pregnancy is associated with reduced peripheral vascular resistance, underpinned by changes in endothelial and smooth muscle function. Failure of the maternal vasculature to adapt correctly leads to serious pregnancy complications, such as preeclampsia. The peptide hormone relaxin regulates the maternal renal vasculature during pregnancy; however, little is known about its effects in other vascular beds. This study tested the hypothesis that functional adaptation of the mesenteric and uterine arteries during pregnancy will be compromised in relaxin-deficient (Rln(-/-)) mice. Smooth muscle and endothelial reactivity were examined in small mesenteric and uterine arteries of nonpregnant (estrus) and late-pregnant (day 17.5) wild-type (Rln(+/+)) and Rln(-/-) mice using wire myography. Pregnancy per se was associated with significant reductions in contraction to phenylephrine, endothelin-1, and ANG II in small mesenteric arteries, while sensitivity to endothelin-1 was reduced in uterine arteries of Rln(+/+) mice. The normal pregnancy-associated attenuation of ANG II-mediated vasoconstriction in mesenteric arteries did not occur in Rln(-/-) mice. This adaptive failure was endothelium-independent and did not result from altered expression of ANG II receptors or regulator of G protein signaling 5 (Rgs5) or increases in reactive oxygen species generation. Inhibition of nitric oxide synthase with l-NAME enhanced ANG II-mediated contraction in mesenteric arteries of both genotypes, whereas blockade of prostanoid production with indomethacin only increased ANG II-induced contraction in arteries of pregnant Rln(+/+) mice. In conclusion, relaxin deficiency prevents the normal pregnancy-induced attenuation of ANG II-mediated vasoconstriction in small mesenteric arteries. This is associated with reduced smooth muscle-derived vasodilator prostanoids. PMID:26936785

  2. Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity

    PubMed Central

    Jammoul, Firas; Wang, Qingping; Nabbout, Rimas; Coriat, Caroline; Duboc, Agnès; Simonutti, Manuel; Dubus, Elisabeth; Craft, Cheryl M.; Ye, Wen; Collins, Stephen D.; Dulac, Olivier; Chiron, Catherine; Sahel, José A.; Picaud, Serge

    2008-01-01

    Objective Although vigabatrin irreversibly constricts the visual field, it remains a potent therapy for infantile spasms and a third-line drug for refractory epilepsies. In albino animals, this drug induces a reduction in retinal cell function, retinal disorganisation and cone photoreceptor damage. The objective of this study was to investigate the light dependence of the vigabatrin-elicited retinal toxicity and to screen for molecules preventing this secondary effect of vigabatrin. Methods Rats and mice were treated daily with vigabatrin 40mg and 3mg, respectively. Retinal cell lesions were demonstrated by assessing cell function with electroretinogram measurements, and quantifying retinal disorganization, gliosis and cone cell densities. Results Vigabatrin-elicited retinal lesions were prevented by maintaining animals in darkness during treatment. Different mechanisms including taurine deficiency were reported to produce such phototoxicity; we therefore measured amino acid plasma levels in vigabatrin-treated animals. Taurine levels were 67% lower in vigabatrin-treated animals than in control animals. Taurine supplementation reduced all components of retinal lesions in both rats and mice. Among 6 vigabatrin-treated infants, the taurine plasma level was found to be below normal in three patients and undetectable in two patients. Interpretation These results indicate that vigabatrin generates a taurine deficiency responsible for its retinal phototoxicity. Future studies will investigate whether co-treatment with taurine and vigabatrin can limit epileptic seizures without inducing the constriction of the visual field. Patients on vigabatrin could gain immediate benefit from reduced light exposures and dietetic advice on taurine-rich foods. PMID:19194884

  3. Bleomycin-induced pulmonary fibrosis is attenuated in gamma-glutamyl transpeptidase-deficient mice.

    PubMed

    Pardo, Annie; Ruiz, Victor; Arreola, José Luis; Ramírez, Remedios; Cisneros-Lira, José; Gaxiola, Miguel; Barrios, Roberto; Kala, Subbarao V; Lieberman, Michael W; Selman, Moisés

    2003-03-15

    To investigate repair mechanisms in bleomycin-induced pulmonary fibrosis, we used mice deficient in gamma-glutamyl transpeptidase (GGT-/-), a key enzyme in glutathione (GSH) and cysteine metabolism. Seventy-two hours after bleomycin (0.03 U/g), GGT-/- mice displayed a different inflammatory response to wild-type mice as judged by a near absence of neutrophils in lung tissue and bronchoalveolar lavage and a less pronounced rise in matrix metalloproteinase-9. Inflammation in GGT-/- mice consisted mainly of lymphocytes and macrophages. At 1 month, lungs from bleomycin-treated GGT-/- mice exhibited minimal areas of fibrosis compared with wild-type mice(light microscopy fibrosis index: 510 +/- 756 versus 1975 +/- 817, p < 0.01). Lung collagen content revealed a significant increase in bleomycin-treated wild-type (15.1 +/- 3.8 versus 8.5 +/- 0.7 microg hydroxy(OH)-proline/mg dry weight, p < 0.01) but not in GGT-/- (10.4 +/- 1.7 versus 8.8 +/- 0.8). Control lungs from GGT-/- showed a significant reduction of cysteine (0.03 +/- 0.005 versus 0.055 +/- 0.001, p < 0.02) and GSH levels (1.24 +/- 0.055 versus 1.79 +/- 0.065, p < 0.002). These values decreased after 72 hours of bleomycin in both GGT-/- and wild-type but reached their respective control values after 1 month. Supplementation with N-acetyl cysteine partially ameliorated the effects of GGT deficiency. These findings suggest that increased neutrophils and matrix metalloproteinase-9 during the early inflammatory response and adequate thiol reserves are key elements in the fibrotic response after bleomycin-induced pulmonary injury. PMID:12468440

  4. Cdc42 deficiency induces podocyte apoptosis by inhibiting the Nwasp/stress fibers/YAP pathway

    PubMed Central

    Huang, Z; Zhang, L; Chen, Y; Zhang, H; Zhang, Q; Li, R; Ma, J; Li, Z; Yu, C; Lai, Y; Lin, T; Zhao, X; Zhang, B; Ye, Z; Liu, S; Wang, W; Liang, X; Liao, R; Shi, W

    2016-01-01

    Podocyte apoptosis is a major mechanism that leads to proteinuria in many chronic kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. The Rho family of small GTPases has been shown to be required in maintaining podocyte structure and function. Recent studies have indicated that podocyte-specific deletion of Cdc42 in vivo, but not of RhoA or Rac1, leads to congenital nephrotic syndrome and glomerulosclerosis. However, the underlying cellular events in podocyte controlled by Cdc42 remain unclear. Here, we assessed the cellular mechanisms by which Cdc42 regulates podocyte apoptosis. We found that the expression of Cdc42 and its activity were significantly decreased in high glucose-, lipopolysaccharide- or adriamycin-injured podocytes. Reduced Cdc42 expression in vitro and in vivo by small interfering RNA and selective Cdc42 inhibitor ML-141, respectively, caused podocyte apoptosis and proteinuria. Our results further demonstrated that insufficient Cdc42 or Nwasp, its downstream effector, could decrease the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Moreover, our data indicated that the loss of stress fibers caused by Cdc42/Nwasp deficiency also decreased Yes-associated protein (YAP) mRNA and protein expression, and induced podocyte apoptosis. Podocyte apoptosis induced by Cdc42/Nwasp/stress fiber deficiency was significantly inhibited by overexpressing-active YAP. Thus, the Cdc42/Nwasp/stress fibers/YAP signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary Cdc42 would be one potent way to prevent proteinuria kidney diseases. PMID:26986510

  5. NLRP3 Deficiency Reduces Macrophage Interleukin-10 Production and Enhances the Susceptibility to Doxorubicin-induced Cardiotoxicity.

    PubMed

    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

  6. Deficiency of interleukin-15 enhances susceptibility to acetaminophen-induced liver injury in mice.

    PubMed

    Hou, Hsein-San; Liao, Ching-Len; Sytwu, Huey-Kang; Liao, Nan-Shih; Huang, Tien-Yu; Hsieh, Tsai-Yuan; Chu, Heng-Cheng

    2012-01-01

    Hepatocytes have a direct necrotic role in acetaminophen (APAP)-induced liver injury (AILI), prolonged secondary inflammatory response through innate immune cells and cytokines also significantly contributes to APAP hepatotoxicity. Interleukin 15 (IL-15), a multifunction cytokine, regulates the adaptive immune system and influences development and function of innate immune cells. To better understand the role of IL-15 in liver injury, we treated wild-type (WT) and IL-15-knockout (Il15⁻/⁻) mice with a hepatotoxic dose of APAP to induce AILI and evaluated animal survival, liver damage, APAP metabolism in livers and the inflammatory response. Production of pro-inflammatory cytokines/chemokines was greater in Il15⁻/⁻ than WT mice. Subanalysis of hepatic infiltrated monocytes revealed greater neutrophil influx, along with greater hepatic induction of inducible nitric oxide synthase (iNOS), in Il15⁻/⁻ than WT mice. In addition, the level of hepatic hemeoxygenase 1 (HO-1) was partially suppressed in Il15⁻/⁻ mice, but not in WT mice. Interestingly, elimination of Kupffer cells and neutrophils did not alter the vulnerability to excess APAP in Il15⁻/⁻ mice. However, injection of galactosamine, a hepatic transcription inhibitor, significantly reduced the increased APAP sensitivity in Il15⁻/⁻ mice but had minor effect on WT mice. We demonstrated that deficiency of IL-15 increased mouse susceptibility to AILI. Moreover, Kupffer cell might affect APAP hepatotoxicity through IL-15. PMID:23028657

  7. 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

  8. Ferric carboxymaltose-mediated attenuation of Doxorubicin-induced cardiotoxicity in an iron deficiency rat model.

    PubMed

    Toblli, Jorge Eduardo; Rivas, Carlos; Cao, Gabriel; Giani, Jorge Fernando; Funk, Felix; Mizzen, Lee; Dominici, Fernando Pablo

    2014-01-01

    Since anthracycline-induced cardiotoxicity (AIC), a complication of anthracycline-based chemotherapies, is thought to involve iron, concerns exist about using iron for anaemia treatment in anthracycline-receiving cancer patients. This study evaluated how intravenous ferric carboxymaltose (FCM) modulates the influence of iron deficiency anaemia (IDA) and doxorubicin (3-5 mg per kg body weight [BW]) on oxidative/nitrosative stress, inflammation, and cardiorenal function in spontaneously hypertensive stroke-prone (SHR-SP) rats. FCM was given as repeated small or single total dose (15 mg iron per kg BW), either concurrent with or three days after doxorubicin. IDA (after dietary iron restriction) induced cardiac and renal oxidative stress (markers included malondialdehyde, catalase, Cu,Zn-superoxide dismutase, and glutathione peroxidase), nitrosative stress (inducible nitric oxide synthase and nitrotyrosine), inflammation (tumour necrosis factor-alpha and interleukin-6), and functional/morphological abnormalities (left ventricle end-diastolic and end-systolic diameter, fractional shortening, density of cardiomyocytes and capillaries, caveolin-1 expression, creatinine clearance, and urine neutrophil gelatinase-associated lipocalin) that were aggravated by doxorubicin. Notably, iron treatment with FCM did not exacerbate but attenuated the cardiorenal effects of IDA and doxorubicin independent of the iron dosing regimen. The results of this model suggest that intravenous FCM can be used concomitantly with an anthracycline-based chemotherapy without increasing signs of AIC. PMID:24876963

  9. Cnr2 Deficiency Confers Resistance to Inflammation-Induced Preterm Birth in Mice

    PubMed Central

    Sun, Xiaofei; Cappelletti, Monica; Li, Yingju; Karp, Christopher L.; Divanovic, Senad

    2014-01-01

    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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Iodine intake and status of UK women of childbearing age recruited at the University of Surrey in the winter.

    PubMed

    Bath, Sarah C; Sleeth, Michelle L; McKenna, Marianne; Walter, Alan; Taylor, Andrew; Rayman, Margaret P

    2014-11-28

    As intra-thyroidal iodine stores should be maximised before conception to facilitate the increased thyroid hormone production during pregnancy, women who are planning to become pregnant should ideally consume 150 μg iodine/d (US RDA). As few UK data exist for this population group, a cross-sectional study was carried out at the University of Surrey to assess the iodine intake and status of women of childbearing age. Total iodine excretion was measured from 24 h urine samples in fifty-seven women; iodine intake was estimated by assuming that 90 % of ingested iodine was excreted. The average iodine intake was also estimated from 48 h food diaries that the participants completed. The median urinary iodine concentration value (63·1 μg/l) indicated the group to be mildly iodine deficient by WHO criteria. By contrast, the median 24 h urinary iodine excretion value (149·8 μg/24 h) indicated a relatively low risk of iodine deficiency. The median estimated iodine intake, extrapolated from urinary excretion, was 167 μg/d, whereas it was lower, at 123 μg/d, when estimated from the 48 h food diaries. Iodine intake estimated from the food diaries and 24 h urinary iodine excretion were strongly correlated (r 0·75, P< 0·001). The 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. The present study highlights the need for revised cut-off values for iodine deficiency that are method- and age group-specific. PMID:25274294

  15. Electron microscopy of low iodinated thyroglobulin molecules.

    PubMed

    Berg, G; Ekholm, R

    1975-04-29

    Thyroglobulin molecules were studied in the electron microscope with negative staining technique. In a first series of experiments samples of thyroglobulin varying in iodine content from 0.5 to 0.03% were prepared from the thyroids of mice and rats kept on iodine-poor diets. All samples contained thyroglobulin molecules of the normal ovoid shape, not deviating in size or shape from molecules obtained from normal thyroids. However, in addition, another type of molecule having a cylindrical shape was observed in all samples. The proportion of these cylindrical molecules increased from a few per cent in the moderately iodine-poor thyroglobulin samples to more than 80% in the highly iodine-deficient thyroglobulin (0.03%). In a second series of experiments extremely iodine-poor thyroglobulin (smaller than 0.005%) was obtained from propylthiouracil-treated rats. In these preparations practically all molecules had a cylindrical shape. These samples also contained smaller particles interpreted to be dissociation products. The cylindrical molecules were of two types, one appearing compact and measuring 250 times 135 A (length times diameter) and the other appearing porous and having a length of 145 and a diameter of 205 A. It is concluded that the cylindrical molecules represent non- or low-iodinated thyroglobulin and it is suggested that the porous cylindrical molecule is an unfolded form of the compact cylinder. PMID:1138879

  16. 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

  17. Evaluation of iodine content and stability in recipes prepared with biofortified potatoes.

    PubMed

    Cerretani, Lorenzo; Comandini, Patrizia; Fumanelli, Davide; Scazzina, Francesca; Chiavaro, Emma

    2014-11-01

    Iodine is an essential micronutrient of the human diet. Deficiency of iodine is diffused in many areas of the world and mild deficiency is present also in developed countries around Europe. Biofortification of vegetables could represent a better strategy with respect to iodized salt in order to increase iodine intake. The aim of this study was evaluating the stability of iodine, derived from biofortified potatoes, in the preparation process of three Italian typical dishes: dumplings, vegetable pie, and focaccia bread. The obtained results showed a good stability of iodine in cooking processes, in particular, during baking of focaccia bread. Significant losses of iodine were detected during boiling of dumplings and baking of vegetable pie. Although the different stability during the cooking processes, the three dishes maintained a good final content of iodine, ranging from the 33.3% to 52.7% of daily recommended intake in adults for individual serving size. PMID:24828007

  18. 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

  19. 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

  20. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice.

    PubMed

    Fuso, Andrea; Nicolia, Vincenzina; Ricceri, Laura; Cavallaro, Rosaria A; Isopi, Elisa; Mangia, Franco; Fiorenza, Maria Teresa; Scarpa, Sigfrido

    2012-07-01

    Methylation reactions linked to homocysteine in the one-carbon metabolism are increasingly elicited in Alzheimer's disease, although the association of hyperhomocysteinemia and of low B vitamin levels with the disease is still debated. We previously demonstrated that hyperhomocysteinemia and DNA hypomethylation induced by B vitamin deficiency are associated with PSEN1 and BACE1 overexpression and amyloid production. The present study is aimed at assessing S-adenosylmethionine effects in mice kept under a condition of B vitamin deficiency. To this end, TgCRND8 mice and wild-type littermates were assigned to control or B vitamin deficient diet, with or without S-adenosylmethionine supplementation. We found that S-adenosylmethionine reduced amyloid production, increased spatial memory in TgCRND8 mice and inhibited the upregulation of B vitamin deficiency-induced PSEN1 and BACE1 expression and Tau phosphorylation in TgCRND8 and wild-type mice. Furthermore, S-adenosylmethionine treatment reduced plaque spreading independently on B vitamin deficiency. These results strengthen our previous observations on the possible role of one-carbon metabolism in Alzheimer's disease, highlighting hyperhomocysteinemia-related mechanisms in dementia onset/progression and encourage further studies aimed at evaluating the use of S-adenosylmethionine as a potential candidate drug for the treatment of the disease. PMID:22221883

  1. [Dysfunction of serotonergic systems in thiamine-deficient diet fed mice: effects of SSRI on abnormality induced by thiamine deficiency].

    PubMed

    Murata, Atsunobu; Nakagawasai, Osamu; Yamadera, Fumihiro; Oba, Akira; Wakui, Kenji; Arai, Yuichiro; Tadano, Takeshi

    2004-04-01

    Mice fed a thiamine deficient (TD) diet, showed some abnormal behaviors such as amnesia and mood abnormality. It is known that several neurons, especially marked in serotonergic neuron, are damaged in humans and rodents in the earlier phase of TD. The symptoms derived from dysfunction of serotonergic neurons are observed in Wernicke-Korsakoff patients (WKS)-derived TD, and it is known that fluvoxamine is effective for WKS. However, the mechanism of this dysfunction is still unclear. For that reason, we studied the relative mechanism between abnormal behaviors and selective dysfunction of serotonergic neurons in TD animals. As a result, this dysfunction by TD is much affected by the brainstem region. But the effect of fluvoxamine on depressive symptoms in WKS patients is not reported; therefore we also studied the effects of fluvoxamine on the depressive behaviors in TD mice as a model of WKS. The increase of immobility time in a forced swimming test as depressive behavior in TD mice was significantly inhibited by fluvoxamine, suggesting an improvable effect on depressive symptoms. With those results of ours, the possible mechanisms between the abnormal behaviors derived from the dysfunction of serotonergic neurons and the role of serotonin in TD and WKS are reviewed here. PMID:15164618

  2. 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

  3. 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

  4. Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer’s mouse model

    PubMed Central

    Karuppagounder, Saravanan S.; Xu, Hui; Shi, Qingli; Chen, Lian H.; Pedrini, Steve; Pechman, David; Baker, Harriet; Beal, M. Flint; Gandy, Sam E.; Gibson, Gary E.

    2009-01-01

    Mitochondrial dysfunction, oxidative stress and reductions in thiamine-dependent enzymes have been implicated in multiple neurological disorders including Alzheimer's disease (AD). Experimental thiamine deficiency (TD) is an established model for reducing the activities of thiamine-dependent enzymes in brain. TD diminishes thiamine dependent enzymes throughout the brain, but produces a time-dependent selective neuronal loss, glial activation, inflammation, abnormalities in oxidative metabolism and clusters of degenerating neurites in only specific thalamic regions. The present studies tested how TD alters brain pathology in Tg19959 transgenic mice over expressing a double mutant form of the amyloid precursor protein (APP). TD exacerbated amyloid plaque pathology in transgenic mice and enlarged the area occupied by plaques in cortex, hippocampus and thalamus by 50%, 200% and 200%, respectively. TD increased Aβ1–42 levels by about three-fold, β-CTF (C99) levels by 33% and β-secretase (BACE1) protein levels by 43%. TD induced inflammation in areas of plaque formation. Thus, the induction of mild impairment of oxidative metabolism, oxidative stress and inflammation induced by TD alters metabolism of APP and/or Aβ and promotes accumulation of plaques independent of neuron loss or neuritic clusters. PMID:18406011

  5. 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

  6. 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. PMID:23781510

  7. 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. PMID:22744648

  8. 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

  9. 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

  10. Nitric Oxide Induction of Parkin Translocation in PTEN-induced Putative Kinase 1 (PINK1) Deficiency

    PubMed Central

    Han, Ji-Young; Kang, Min-Ji; Kim, Kyung-Hee; Han, Pyung-Lim; Kim, Hyun-Seok; Ha, Ji-Young; Son, Jin H.

    2015-01-01

    The failure to trigger mitophagy is implicated in the pathogenesis of familial Parkinson disease that is caused by PINK1 or Parkin mutations. According to the prevailing PINK1-Parkin signaling model, mitophagy is promoted by the mitochondrial translocation of Parkin, an essential PINK1-dependent step that occurs via a previously unknown mechanism. Here we determined that critical concentrations of NO was sufficient to induce the mitochondrial translocation of Parkin even in PINK1 deficiency, with apparent increased interaction of full-length PINK1 accumulated during mitophagy, with neuronal nitric oxide synthase (nNOS). Specifically, optimum levels of NO enabled PINK1-null dopaminergic neuronal cells to regain the mitochondrial translocation of Parkin, which appeared to be significantly suppressed by nNOS-null mutation. Moreover, nNOS-null mutation resulted in the same mitochondrial electron transport chain (ETC) enzyme deficits as PINK1-null mutation. The involvement of mitochondrial nNOS activation in mitophagy was further confirmed by the greatly increased interactions of full-length PINK1 with nNOS, accompanied by mitochondrial accumulation of phospho-nNOS (Ser1412) during mitophagy. Of great interest is that the L347P PINK1 mutant failed to bind to nNOS. The loss of nNOS phosphorylation and Parkin accumulation on PINK1-deficient mitochondria could be reversed in a PINK1-dependent manner. Finally, non-toxic levels of NO treatment aided in the recovery of PINK1-null dopaminergic neuronal cells from mitochondrial ETC enzyme deficits. In summary, we demonstrated the full-length PINK1-dependent recruitment of nNOS, its activation in the induction of Parkin translocation, and the feasibility of NO-based pharmacotherapy for defective mitophagy and ETC enzyme deficits in Parkinson disease. PMID:25716315

  11. ACETAMINOPHEN-INDUCED HEPATIC NEUTROPHIL ACCUMULATION AND INFLAMMATORY LIVER INJURY IN CD18-DEFICIENT MICE

    PubMed Central

    Williams, C. David; Bajt, Mary Lynn; Farhood, Anwar; Jaeschke, Hartmut

    2014-01-01

    Background Acetaminophen (APAP) hepatotoxicity is currently the most frequent cause of acute liver failure in the US and many European countries. Although intracellular signaling mechanisms are critical for hepatocellular injury, a contribution of inflammatory cells, especially neutrophils, has been suggested. However, conflicting results were obtained when using immunological intervention strategies. Aims The role of neutrophils was investigated using a CD18-deficient mouse model. Results Treatment of C57Bl/6 wild type mice with 300 mg/kg APAP resulted in severe liver cell necrosis at 12 and 24 h. This injury was accompanied by formation of cytokines and chemokines and accumulation of neutrophils in the liver. However, there was no difference in the inflammatory response or liver injury in CD18-deficient mice compared to wild type animals. In contrast to treatment with endotoxin, no upregulation of CD11b or priming for reactive oxygen was observed on neutrophils isolated from the peripheral blood or the liver after APAP administration. Furthermore, animals treated with endotoxin 3 h after APAP experienced an exaggerated inflammatory response as indicated by substantially higher cytokine and chemokine formation and twice the number of neutrophils in the liver. However, liver injury in the two-hit model was the same as with APAP alone. Conclusions Our data do not support the hypothesis that neutrophils contribute to APAP hepatotoxicity or that a neutrophil-mediated injury phase could be provoked by a second, pro-inflammatory hit. Thus, APAP-induced liver injury in mice is dominated by intracellular mechanisms of cell death rather than by neutrophilic inflammation. PMID:20500806

  12. Autophagy deficiency in myeloid cells increases susceptibility to obesity-induced diabetes and experimental colitis.

    PubMed

    Lee, Hae-Youn; Kim, Jinyoung; Quan, Wenying; Lee, June-Chul; Kim, Min-Soo; Kim, Seok-Hyung; Bae, Jin-Woo; Hur, Kyu Yeon; Lee, Myung-Shik

    2016-08-01

    Autophagy, which is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria, affects diverse aspects of metabolism, and its dysregulation has been incriminated in various metabolic disorders. However, the role of autophagy of myeloid cells in adipose tissue inflammation and type 2 diabetes has not been addressed. We produced mice with myeloid cell-specific deletion of Atg7 (autophagy-related 7), an essential autophagy gene (Atg7 conditional knockout [cKO] mice). While Atg7 cKO mice were metabolically indistinguishable from control mice, they developed diabetes when bred to ob/w mice (Atg7 cKO-ob/ob mice), accompanied by increases in the crown-like structure, inflammatory cytokine expression and inflammasome activation in adipose tissue. Mφs (macrophages) from Atg7 cKO mice showed significantly higher interleukin 1 β release and inflammasome activation in response to a palmitic acid plus lipopolysaccharide combination. Moreover, a decrease in the NAD(+):NADH ratio and increase in intracellular ROS content after treatment with palmitic acid in combination with lipopolysaccharide were more pronounced in Mφs from Atg7 cKO mice, suggesting that mitochondrial dysfunction in autophagy-deficient Mφs leads to an increase in lipid-induced inflammasome and metabolic deterioration in Atg7 cKO-ob/ob mice. Atg7 cKO mice were more susceptible to experimental colitis, accompanied by increased colonic cytokine expression, T helper 1 skewing and systemic bacterial invasion. These results suggest that autophagy of Mφs is important for the control of inflammasome activation in response to metabolic or extrinsic stress, and autophagy deficiency in Mφs may contribute to the progression of metabolic syndrome associated with lipid injury and colitis. PMID:27337687

  13. Evaluation of Intrarenal Oxygenation in Iodinated Contrast-Induced Acute Kidney Injury–Susceptible Rats by Blood Oxygen Level–Dependent Magnetic Resonance Imaging

    PubMed Central

    Li, Lu-Ping; Lu, Jing; Zhou, Ying; Papadopoulou, Maria V.; Franklin, Tammy; Bokhary, Ujala; Solomon, Richard; Sen, Anindya; Prasad, Pottumarthi V.

    2016-01-01

    Objectives The objectives of this study were to evaluate differences in intrarenal oxygenation as assessed by blood oxygen level–dependent (BOLD) magnetic resonance imaging in contrast-induced acute kidney injury (CIAKI)–susceptible rats when using 4 contrast media with different physicochemical properties and to demonstrate the feasibility of acquiring urinary neutrophil gelatinase–associated lipocalin (NGAL) levels as a marker of CIAKI in this model. Materials and Methods Our institutional animal care and use committee approved the study. Sixty-six Sprague-Dawley rats were divided into CIAKI-susceptible groups (received nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester [10 mg/kg] and cycloxygenase inhibitor indomethacin [10mg/kg]) and control groups (received saline instead). One of the 4 iodinated contrast agents (iothalamate, iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram of body weight). Multiple blood oxygen level–dependent magnetic resonance images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after N-nitro-L-arginine methyl ester (or saline), indomethacin (or saline), and iodinated contrast agent (or placebo). R2* (R2* = 1/T2*) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of kidney injury (unlike serum creatinine), was measured 4 hours after contrast injection in the 2 subgroups. Results Differences in blood oxygen level–dependent magnetic resonance imaging results between the contrast media were observed in all 4 renal regions. However, the inner stripe of the outer medulla (ISOM) showed the most pronounced changes in the CIAKI-susceptible group and R2* increased significantly (P < 0.01) over time with all 4 contrast media. In the control groups, only iodixanol showed an increase in R2

  14. 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

  15. 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

  16. 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. PMID:25131448

  17. 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

  18. 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

  19. RMI1 deficiency in mice protects from diet and genetic-induced obesity.

    PubMed

    Suwa, Akira; Yoshino, Masayasu; Yamazaki, Chihiro; Naitou, Masanori; Fujikawa, Rie; Matsumoto, Shun-Ichiro; Kurama, Takeshi; Shimokawa, Teruhiko; Aramori, Ichiro

    2010-02-01

    The aim of this study is to discover and characterize novel energy homeostasis-related molecules. We screened stock mouse embryonic stem cells established using the exchangeable gene trap method, and examined the effects of deficiency of the target gene on diet and genetic-induced obesity. The mutant strain 0283, which has an insertion at the recQ-mediated genome instability 1 (RMI1) locus, possesses a number of striking features that allow it to resist metabolic abnormalities. Reduced RMI1 expression, lower fasting-blood glucose and a reduced body weight (normal diet) were observed in the mutant mice. When fed a high-fat diet, the mutant mice were resistant to obesity, and also showed improved glucose intolerance and reduced abdominal fat tissue mass and food intake. In addition, the mutants were also resistant to obesity induced by the lethal yellow agouti (A(y)) gene. Endogenous RMI1 genes were found to be up-regulated in the liver and adipose tissue of KK-A(y) mice. RMI1 is a component of the Bloom's syndrome gene helicase complex that maintains genome integrity and activates cell-cycle checkpoint machinery. Interestingly, diet-induced expression of E2F8 mRNA, which is an important cell cycle-related molecule, was suppressed in the mutant mice. These results suggest that the regulation of energy balance by RMI1 is attributable to the regulation of food intake and E2F8 expression in adipose tissue. Taken together, these findings demonstrate that RMI1 is a novel molecule that regulates energy homeostasis. PMID:20050919

  20. 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

  1. 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)

  2. 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.

  3. MicroRNA-155 deficiency promotes nephrin acetylation and attenuates renal damage in hyperglycemia-induced nephropathy.

    PubMed

    Lin, Xu; You, Yanwu; Wang, Jie; Qin, Youling; Huang, Peng; Yang, Fafen

    2015-04-01

    MiR-155 has been reported to be involved in both innate and adaptive immune responses. But the role of miR-155 in hyperglycemia-induced nephropathy is still unknown. In our current study, 3-month-old male wild-type C57 mice and Mir-155(-/-) mice were used to establish hyperglycemia-induced nephropathy. In our hyperglycemia-induced nephropathy model, the expression of podocyte injury marker desmin was markedly increased in the diabetes group when compared with control. Diabetes also significantly decreased the levels of nephrin and acetylated nephrin, whereas the expression of miR-155 was markedly increased in diabetes group when compared with control. MiR-155(-/-) mice showed significantly increased expression of nephrin, acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with wild-type control. MiR-155 deficiency results in significantly decrease in IL-17A expression both in vivo and in vitro. And the increased expression of WT-1, nephrin, and ac-nephrin was reversed with additional treatment of rmIL-17. Furthermore, we found that the inhibited Th17 differentiation induced by miR-155 deficiency was dependent on increased expression of SOCS1. In conclusion, miR-155 deficiency promotes nephrin acetylation and attenuates renal damage in hyperglycemia-induced nephropathy. This was associated with inhibited IL-17 production through enhancement of SOCS1 expression. PMID:24969676

  4. 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

  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. 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. PMID:23782592

  7. 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.

  8. 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

  9. Vitamin B-12 deficiency induces anomalies of base substitution and methylation in the DNA of rat colonic epithelium.

    PubMed

    Choi, Sang-Woon; Friso, Simonetta; Ghandour, Haifa; Bagley, Pamela J; Selhub, Jacob; Mason, Joel B

    2004-04-01

    Derangements of one-carbon metabolism can directly affect the integrity of the genome by producing inappropriate uracil insertion into DNA and by altering patterns of DNA methylation. Vitamin B-12, a one-carbon nutrient, serves as a cofactor in the synthesis of precursors of biological methylation and in nucleotide synthesis. We therefore examined whether vitamin B-12 deficiency can induce these molecular anomalies in the colonic mucosa of rats. Weanling male Sprague-Dawley rats (n = 30) were divided into 2 groups and fed either a vitamin B-12-deficient diet or a similar diet containing adequate amounts of the vitamin. Rats from each group were killed at 6 and 10 wk. Uracil misincorporation into DNA was measured by GC/MS and genomic DNA methylation was measured by LC/MS. Plasma vitamin B-12 concentrations in deficient rats were below detectable limits at 6 and 10 wk; in control rats, concentrations were 0.46 +/- 0.07 and 0.42 +/- 0.10 nmol/L at those times. Although the colon total folate concentration did not differ between the groups, the proportion that was methylfolate was marginally greater in the deficient rats at 10 wk (P = 0.05) compared with control, consistent with the "methylfolate trap" that develops during vitamin B-12 deficiency. After 10 wk, the colonic DNA of the deficient rats displayed a 35% decrease in genomic methylation and a 105% increase in uracil incorporation (P < 0.05). This vitamin B-12-deficient diet, which was of insufficient severity to cause anemia or illness, created aberrations in both base substitution and methylation of colonic DNA, which might increase susceptibility to carcinogenesis. PMID:15051821

  10. Zinc deficiency induces apoptosis via mitochondrial p53- and caspase-dependent pathways in human neuronal precursor cells.

    PubMed

    Seth, Rohit; Corniola, Rikki S; Gower-Winter, Shannon D; Morgan, Thomas J; Bishop, Brian; Levenson, Cathy W

    2015-04-01

    Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. Disruption of mitochondrial membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species (ROS) after 24h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved. Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin-μ, established that these alterations were largely dependent on p53. Together these data identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated mechanisms leading to apoptosis during zinc deficiency. PMID:25467851

  11. Restraint stress induces and exacerbates intestinal inflammation in interleukin-10 deficient mice

    PubMed Central

    Koh, Seong-Joon; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Kim, Joo Sung

    2015-01-01

    AIM: To investigate the effects of restraint stress on chronic colitis in interleukin (IL)-10 deficient (IL-10-/-) mice. METHODS: The first experiment compared the effect of restraint stress on the development of intestinal inflammation in wild-type and IL-10-/- mice. Both wild-type and IL-10-/- mice were physically restrained in a well-ventilated, 50 cm3 conical polypropylene tube for 2 h per day for three consecutive days. The second experiment was performed to assess the effect of restraint stress on exacerbation of colitis induced by piroxicam in IL-10-/- mice. The IL-10-/- mice were exposed to restraint stress for 2 h per day for 3 consecutive days, and then treated with piroxicam for 4 d at a dose of 200 ppm administered in the rodent chow. RESULTS: In the first experiment, none of the wild-type mice with or without restraint stress showed clinical and histopathological abnormality in the gut. However, IL-10-/- mice exposed to restraint stress exhibited histologically significant intestinal inflammation as compared to those without restraint stress. In the second experiment, restraint stress significantly reduced body weight and increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10-/- mice. Colonic IL12p40 mRNA expression was strongly increased in mice exposed to restraint stress. CONCLUSION: This novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease. PMID:26229400

  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. Lead phytotoxicity in soils and nutrient solutions is related to lead induced phosphorus deficiency.

    PubMed

    Cheyns, Karlien; Peeters, Sofie; Delcourt, Dorien; Smolders, Erik

    2012-05-01

    This study was set up to relate lead (Pb) bioavailability with its toxicity to plants in soils. Tomato and barley seedlings were grown in six different PbCl(2) spiked soils (pH: 4.7-7.4; eCEC: 4.2-41.7 cmol(c)/kg). Soils were leached and pH corrected after spiking to exclude confounding factors. Plant growth was halved at 1600-6500 mg Pb/kg soil for tomato and at 1900-8300 mg Pb/kg soil for barley. These soil Pb threshold were unrelated to soil pH, organic carbon, texture or eCEC and neither soil solution Pb nor Pb(2+) ion activity adequately explained Pb toxicity among soils. Shoot phosphorus (P) concentrations significantly decreased with increasing soil Pb concentrations. Tomato grown in hydroponics at either varying P supply or at increasing Pb (equal initial P) illustrated that shoot P explained growth response in both scenarios. The results suggest that Pb toxicity is partially related to Pb induced P deficiency, likely due to lead phosphate precipitation. PMID:22377902

  14. 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

  15. Calvarial Cleidocraniodysplasia-like defects with ENU-induced Nell-1 deficiency

    PubMed Central

    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

    2011-01-01

    NELL-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. In order 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 (CCD). 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, while 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. PMID:22337375

  16. 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. PMID:22337375

  17. Myostatin deficiency but not anti-myostatin blockade induces marked proteomic changes in mouse skeletal muscle.

    PubMed

    Salzler, Robert R; Shah, Darshit; Doré, Anthony; Bauerlein, Roy; Miloscio, Lawrence; Latres, Esther; Papadopoulos, Nicholas J; Olson, William C; MacDonald, Douglas; Duan, Xunbao

    2016-07-01

    Pharmacologic blockade of the myostatin (Mstn)/activin receptor pathway is being pursued as a potential therapy for several muscle wasting disorders. The functional benefits of blocking this pathway are under investigation, in particular given the findings that greater muscle hypertrophy results from Mstn deficiency arising from genetic ablation compared to post-developmental Mstn blockade. Using high-resolution MS coupled with SILAC mouse technology, we quantitated the relative proteomic changes in gastrocnemius muscle from Mstn knockout (Mstn(-/-) ) and mice treated for 2-weeks with REGN1033, an anti-Mstn antibody. Relative to wild-type animals, Mstn(-/-) mice had a two-fold greater muscle mass and a >1.5-fold change in expression of 12.0% of 1137 quantified muscle proteins. In contrast, mice treated with REGN1033 had minimal changes in muscle proteome (0.7% of 1510 proteins >1.5-fold change, similar to biological difference 0.5% of 1310) even though the treatment induced significant 20% muscle mass increase. Functional annotation of the altered proteins in Mstn(-/-) mice corroborates the mutiple physiological changes including slow-to-fast fiber type switch. Thus, the proteome-wide protein expression differs between Mstn(-/-) mice and mice subjected to specific Mstn blockade post-developmentally, providing molecular-level insights to inform mechanistic hypotheses to explain the observed functional differences. PMID:27214824

  18. 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.

  19. 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.

  20. Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature

    PubMed Central

    Taccioli, C; Chen, H; Jiang, Y; Liu, XP; Huang, K; Smalley, KJ; Farber, JL; Croce, CM; Fong, LY

    2011-01-01

    Chronic inflammation is implicated in the pathogenesis of esophageal squamous cell cancer (ESCC). The causes of inflammation in ESCC, however, are undefined. Dietary zinc-deficiency (ZD) increases the risk of ESCC. We have previously shown that short-term ZD (6 weeks) in rats induces overexpression of the proinflammatory mediators S100a8 and S100a9 in the esophageal mucosa with accompanying esophageal epithelial hyperplasia. Here we report that prolonged ZD (21 weeks) in rats amplified this inflammation that when combined with non-carcinogenic low doses of the environmental carcinogen N-nitrosomethylbenzylamine (NMBA) elicited a 66.7% (16/24) incidence of ESCC. With zinc-sufficiency NMBA produced no cancers (0/21) (P<0.001). At tumor endpoint, the neoplastic ZD esophagus as compared with zinc-sufficient esophagus had an inflammatory gene signature with upregulation of numerous cancer-related inflammation genes (CXC and CC chemokines, chemokine receptors, cytokines, and Cox-2) in addition to S100a8 and S100a9. This signature was already activated in the earlier dysplastic stage. Additionally, time-course bioinformatics analysis of expression profiles at tumor endpoint and prior to NMBA exposure revealed that this sustained inflammation was due to ZD rather than carcinogen exposure. Importantly, zinc replenishment reversed this inflammatory signature at both the dysplastic and neoplastic stages of ESCC development, and prevented cancer formation. Thus, the molecular definition of ZD-induced inflammation as a critical factor in ESCC development has important clinical implications with regard to development and prevention of this deadly disease. PMID:22179833

  1. Fatty Acid Binding Protein 4 Deficiency Protects against Oxygen-Induced Retinopathy in Mice

    PubMed Central

    Saint-Geniez, Magali; Ghelfi, Elisa; Liang, Xiaoliang; Yu, Chenwei; Spencer, Carrie; Abend, Stephanie; Hotamisligil, Gokhan; Cataltepe, Sule

    2014-01-01

    Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide due to increasing survival rates of premature infants. Initial suppression, followed by increased production of the retinal vascular endothelial growth factor-A (VEGF) expression are key events that trigger the pathological neovascularization in ROP. Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone that is induced by VEGF in a subset of endothelial cells. FABP4 exhibits a pro-angiogenic function in cultured endothelial cells and in airway microvasculature, but whether it plays a role in modulation of retinal angiogenesis is not known. We hypothesized that FABP4 deficiency could ameliorate pathological retinal vascularization and investigated this hypothesis using a well-characterized mouse model of oxygen-induced retinopathy (OIR). We found that FABP4 was not expressed in retinal vessels, but was present in resident macrophages/microglial cells and endothelial cells of the hyaloid vasculature in the immature retina. While FABP4 expression was not required for normal development of retinal vessels, FABP4 expression was upregulated and localized to neovascular tufts in OIR. FABP4−/− mice demonstrated a significant decrease in neovessel formation as well as a significant improvement in physiological revascularization of the avascular retinal tissues. These alterations in retinal vasculature were accompanied by reduced endothelial cell proliferation, but no effect on apoptosis or macrophage/microglia recruitment. FABP4−/− OIR samples demonstrated decreased expression of genes involved in angiogenesis, such as Placental Growth Factor, and angiopoietin 2. Collectively, our findings suggest FABP4 as a potential target of pathologic retinal angiogenesis in proliferative retinopathies. PMID:24802082

  2. Fatty acid binding protein 4 deficiency protects against oxygen-induced retinopathy in mice.

    PubMed

    Saint-Geniez, Magali; Ghelfi, Elisa; Liang, Xiaoliang; Yu, Chenwei; Spencer, Carrie; Abend, Stephanie; Hotamisligil, Gokhan; Cataltepe, Sule

    2014-01-01

    Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide due to increasing survival rates of premature infants. Initial suppression, followed by increased production of the retinal vascular endothelial growth factor-A (VEGF) expression are key events that trigger the pathological neovascularization in ROP. Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone that is induced by VEGF in a subset of endothelial cells. FABP4 exhibits a pro-angiogenic function in cultured endothelial cells and in airway microvasculature, but whether it plays a role in modulation of retinal angiogenesis is not known. We hypothesized that FABP4 deficiency could ameliorate pathological retinal vascularization and investigated this hypothesis using a well-characterized mouse model of oxygen-induced retinopathy (OIR). We found that FABP4 was not expressed in retinal vessels, but was present in resident macrophages/microglial cells and endothelial cells of the hyaloid vasculature in the immature retina. While FABP4 expression was not required for normal development of retinal vessels, FABP4 expression was upregulated and localized to neovascular tufts in OIR. FABP4-/- mice demonstrated a significant decrease in neovessel formation as well as a significant improvement in physiological revascularization of the avascular retinal tissues. These alterations in retinal vasculature were accompanied by reduced endothelial cell proliferation, but no effect on apoptosis or macrophage/microglia recruitment. FABP4-/- OIR samples demonstrated decreased expression of genes involved in angiogenesis, such as Placental Growth Factor, and angiopoietin 2. Collectively, our findings suggest FABP4 as a potential target of pathologic retinal angiogenesis in proliferative retinopathies. PMID:24802082

  3. Induced expression of nucleolin phosphorylation-deficient mutant confers dominant-negative effect on cell proliferation.

    PubMed

    Xiao, Shu; Caglar, Elif; Maldonado, Priscilla; Das, Dibash; Nadeem, Zaineb; Chi, Angela; Trinité, Benjamin; Li, Xin; Saxena, Anjana

    2014-01-01

    Nucleolin (NCL) is a major nucleolar phosphoprotein that has pleiotropic effects on cell proliferation and is elevated in a variety of tumors. NCL is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2) and mitotic cyclin-dependent kinase 1 (CDK1). Earlier we demonstrated that a NCL-mutant that is partly defective in undergoing phosphorylation by CK2 inhibits chromosomal replication through its interactions with Replication Protein A, mimicking the cellular response to DNA damage. We further delineated that the N-terminus of NCL associates with Hdm2, the most common E3 ubiquitin ligase of p53. We reported that NCL antagonizes Hdm2 to stabilize p53 and stimulates p53 transcriptional activity. Although NCL-phosphorylation by CK2 and ribosomal DNA transcription are closely coordinated during interphase, the role of NCL phosphorylation in regulating cell proliferation remains unexplored. We have therefore engineered unique human cells that specifically induce expression of NCL-wild type (WT) or a phosphorylation-deficient NCL-mutant, 6/S*A where all the six CK2 consensus serine sites residing in the N-terminus NCL were mutated to alanine. Here we show that this NCL-mutant is defective in undergoing phosphorylation by CK2. We also demonstrate that NCL-phosphorylation by CK2 is required through the S-phase progression in cell cycle and hence proliferation. Induced expression of NCL with mutated CK2 phosphorylation sites stabilizes p53, results in higher expression of Bcl2 (B-cell lymphoma 2) homology 3 (BH3)-only apoptotic markers and causes a dominant-negative effect on cell viability. Our unique cellular system thus provides the first evidential support to delineate phospho-specific functions of NCL on cell proliferation. PMID:25313645

  4. Oxidative stress responses and root lignification induced by Fe deficiency conditions in pear and quince genotypes.

    PubMed

    Donnini, Silvia; Dell'Orto, Marta; Zocchi, Graziano

    2011-01-01

    We analysed Pyrus communis cv. Conference and Cydonia oblonga BA29, differently tolerant to lime-induced chlorosis, to identify the key mechanisms involved in their different performance under Fe deficiency induced by the absence of Fe (-Fe) or by the presence of bicarbonate (+FeBic). Under our experimental conditions, a decrease in root elongation was observed in BA29 under bicarbonate supply. Superoxide dismutase (SOD) and peroxidase (POD) activities were analysed and the relative isoforms were detected by native electrophoresis. The data obtained for both genotypes under -Fe and for BA29 +FeBic suggest the occurrence of overproduction of reactive oxygen species (ROS) and, at the same time, of a scarce capacity to detoxify them. The detection of ROS (O(2)(-) and H(2)O(2)) through histochemical localization supports these results and suggests that they could account for the modifications of mechanical properties of the cell wall during stress adaptation. On the other hand, in the cv. Conference +FeBic, an increase in non-specific POD activity was detected, confirming its higher level of protection in particular against H(2)O(2) accumulation. Peroxidases involved in lignification were assayed and histochemical analysis was performed. The results suggest that only in BA29 under bicarbonate supply can the presence of ROS in root apoplast be correlated with lignin deposits in external layers and in endodermis as a consequence of the shift of PODs towards a lignification role. We suggest that in BA29 the decrease in root growth could impair mineral nutrition, generating susceptibility to calcareous soils. In the cv. Conference, the allocation of new biomass to the root system could improve soil exploration and consequently Fe uptake. PMID:21389006

  5. Induced Expression of Nucleolin Phosphorylation-Deficient Mutant Confers Dominant-Negative Effect on Cell Proliferation

    PubMed Central

    Xiao, Shu; Caglar, Elif; Maldonado, Priscilla; Das, Dibash; Nadeem, Zaineb; Chi, Angela; Trinité, Benjamin; Li, Xin; Saxena, Anjana

    2014-01-01

    Nucleolin (NCL) is a major nucleolar phosphoprotein that has pleiotropic effects on cell proliferation and is elevated in a variety of tumors. NCL is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2) and mitotic cyclin-dependent kinase 1 (CDK1). Earlier we demonstrated that a NCL-mutant that is partly defective in undergoing phosphorylation by CK2 inhibits chromosomal replication through its interactions with Replication Protein A, mimicking the cellular response to DNA damage. We further delineated that the N-terminus of NCL associates with Hdm2, the most common E3 ubiquitin ligase of p53. We reported that NCL antagonizes Hdm2 to stabilize p53 and stimulates p53 transcriptional activity. Although NCL-phosphorylation by CK2 and ribosomal DNA transcription are closely coordinated during interphase, the role of NCL phosphorylation in regulating cell proliferation remains unexplored. We have therefore engineered unique human cells that specifically induce expression of NCL-wild type (WT) or a phosphorylation-deficient NCL-mutant, 6/S*A where all the six CK2 consensus serine sites residing in the N-terminus NCL were mutated to alanine. Here we show that this NCL-mutant is defective in undergoing phosphorylation by CK2. We also demonstrate that NCL-phosphorylation by CK2 is required through the S-phase progression in cell cycle and hence proliferation. Induced expression of NCL with mutated CK2 phosphorylation sites stabilizes p53, results in higher expression of Bcl2 (B-cell lymphoma 2) homology 3 (BH3)-only apoptotic markers and causes a dominant-negative effect on cell viability. Our unique cellular system thus provides the first evidential support to delineate phospho-specific functions of NCL on cell proliferation. PMID:25313645

  6. Endothelial Nitric Oxide Synthase Deficient Mice Are Protected from Lipopolysaccharide Induced Acute Lung Injury

    PubMed Central

    Gross, Christine M.; Rafikov, Ruslan; Kumar, Sanjiv; Aggarwal, Saurabh; Ham III, P. Benson; Meadows, Mary Louise; Cherian-Shaw, Mary; Kangath, Archana; Sridhar, Supriya; Lucas, Rudolf; Black, Stephen M.

    2015-01-01

    Lipopolysaccharide (LPS) derived from the outer membrane of gram-negative bacteria induces acute lung injury (ALI) in mice. This injury is associated with lung edema, inflammation, diffuse alveolar damage, and severe respiratory insufficiency. We have previously reported that LPS-mediated nitric oxide synthase (NOS) uncoupling, through increases in asymmetric dimethylarginine (ADMA), plays an important role in the development of ALI through the generation of reactive oxygen and nitrogen species. Therefore, the focus of this study was to determine whether mice deficient in endothelial NOS (eNOS-/-) are protected against ALI. In both wild-type and eNOS-/- mice, ALI was induced by the intratracheal instillation of LPS (2 mg/kg). After 24 hours, we found that eNOS-/-mice were protected against the LPS mediated increase in inflammatory cell infiltration, inflammatory cytokine production, and lung injury. In addition, LPS exposed eNOS-/- mice had increased oxygen saturation and improved lung mechanics. The protection in eNOS-/- mice was associated with an attenuated production of NO, NOS derived superoxide, and peroxynitrite. Furthermore, we found that eNOS-/- mice had less RhoA activation that correlated with a reduction in RhoA nitration at Tyr34. Finally, we found that the reduction in NOS uncoupling in eNOS-/- mice was due to a preservation of dimethylarginine dimethylaminohydrolase (DDAH) activity that prevented the LPS-mediated increase in ADMA. Together our data suggest that eNOS derived reactive species play an important role in the development of LPS-mediated lung injury. PMID:25786132

  7. 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. PMID:26144993

  8. Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells

    PubMed Central

    2012-01-01

    Background The high cost and low level of cancer survival urge the finding of new drugs having better mechanisms. There is a high trend of patients to be “back to nature” and use natural products as an alternative way to cure cancer. The fact is that some of available anticancer drugs are originated from plants, such as taxane, vincristine, vinblastine, pacitaxel. Curcumin (diferuloylmethane), a dietary pigment present in Curcuma longa rizhome is reported to induce cell cycle arrest in some cell lines. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. The inhibition of cdk1 phosphorylation is one of alternative strategy which could selectively kill cancer cells and potentially be combined with DNA damaging agent such as curcumin. Methods T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining. Results In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10 μM. Increasing concentration up to 30 μM increased the number of cell death. Whilst genistein alone at low concentration (≤10 μM) induced cell proliferation, addition of genistein (20 μM) 16 h after curcumin resulted in more cell death (89%), 34% higher than that administered at the same time (56%). The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50 μM) induced necrotic cells. Conclusions Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of treatment and this method

  9. 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

  10. 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

  11. 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

  12. Reduced endoplasmic reticulum stress-induced apoptosis and impaired unfolded protein response in TRPC3-deficient M1 macrophages

    PubMed Central

    Solanki, Sumeet; Dube, Prabhatchandra R.; Tano, Jean-Yves; Birnbaumer, Lutz

    2014-01-01

    Endoplasmic reticulum (ER) stress is a prominent mechanism of macrophage apoptosis in advanced atherosclerotic lesions. Recent studies from our laboratory showed that advanced atherosclerotic plaques in Apoe−/− mice with bone marrow deficiency of the calcium-permeable channel Transient Receptor Potential Canonical 3 (TRPC3) are characterized by reduced areas of necrosis and fewer apoptotic macrophages than animals transplanted with Trpc3+/+ bone marrow. In vitro, proinflammatory M1 but not anti-inflammatory M2 macrophages derived from Trpc3−/−Apoe−/− animals exhibited reduced ER stress-induced apoptosis. However, whether this was due to a specific effect of TRPC3 deficiency on macrophage ER stress signaling remained to be determined. In the present work we used polarized macrophages derived from mice with macrophage-specific deficiency of TRPC3 to examine the expression level of ER stress markers and the activation status of some typical mediators of macrophage apoptosis. We found that the reduced susceptibility of TRPC3-deficient M1 macrophages to ER stress-induced apoptosis correlates with an impaired unfolded protein response (UPR), reduced mitochondrion-dependent apoptosis, and reduced activation of the proapoptotic molecules calmodulin-dependent protein kinase II and signal transducer and activator of transcription 1. Notably, none of these pathways was altered in TRPC3-deficient M2 macrophages. These findings show for the first time an obligatory requirement for a member of the TRPC family of cation channels in ER stress-induced apoptosis in macrophages, underscoring a rather selective role of the TRPC3 channel on mechanisms related to the UPR signaling in M1 macrophages. PMID:25031020

  13. Sources of dietary iodine: bread, cows' milk, and infant formula in the Boston area.

    PubMed

    Pearce, Elizabeth N; Pino, Sam; He, Xuemei; Bazrafshan, Hamid R; Lee, Stephanie L; Braverman, Lewis E

    2004-07-01

    Dietary iodine is essential for thyroid hormone production. Although U.S. dietary iodine is generally adequate, some groups, especially women of childbearing age, are at risk for mild iodine deficiency. Children's average urinary iodine is higher than that of adults. U.S. dietary iodine sources have not been assessed recently. A survey of iodine content in 20 brands of bread, 18 brands of cows' milk, and eight infant formulae was performed between 2001 and 2002. Three bread varieties contained more than 300 microg iodine per slice. Iodine content in other brands was far lower (mean +/- sd, 10.1 +/- 13.2 microg iodine/slice). All cows' milk samples had at least 88 microg iodine/250 ml, ranging from 88-168 microg (116.0 +/- 22.1 microg/250 ml). Infant formulae values ranged from 16.2 to 56.8 microg iodine/5 oz (23.5 +/- 13.78 microg/5 oz). The public should be aware of the need for adequate dietary iodine intake and should be aware that ingredient lists do not reflect the iodine content of foods. PMID:15240625

  14. 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

  15. CD47 Deficiency Protects Mice From Diet-induced Obesity and Improves Whole Body Glucose Tolerance and Insulin Sensitivity

    PubMed Central

    Maimaitiyiming, Hasiyeti; Norman, Heather; Zhou, Qi; Wang, Shuxia

    2015-01-01

    CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were protected from HF diet-induced obesity displaying decreased weight gain and reduced adiposity. This led to decreased MCP1/CCR2 dependent macrophage infiltration into adipose tissue and reduced inflammation, resulting in improved glucose tolerance and insulin sensitivity. In addition, CD47 deficiency stimulated the expression of UCP1 and carnitine palmitoyltransferase 1b (CPT1b) levels in brown adipose tissue, leading to increased lipid utilization and heat production. This contributes to the increased energy utilization and reduced adiposity observed in these mice. Taken together, these data revealed a novel role for CD47 in the development of obesity and its related metabolic complications. PMID:25747123

  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. Sigma-1 receptor deficiency reduces MPTP-induced parkinsonism and death of dopaminergic neurons

    PubMed Central

    Hong, J; Sha, S; Zhou, L; Wang, C; Yin, J; Chen, L

    2015-01-01

    Sigma-1 receptor (σ1R) has been reported to be decreased in nigrostriatal motor system of Parkinson's disease patients. Using heterozygous and homozygous σ1R knockout (σ1R+/− and σ1R−/−) mice, we investigated the influence of σ1R deficiency on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-impaired nigrostriatal motor system. The injection of MPTP for 5 weeks in wild-type mice (MPTP-WT mice), but not in σ1R+/− or σ1R−/− mice (MPTP-σ1R+/− or MPTP-σ1R−/− mice), caused motor deficits and ~40% death of dopaminergic neurons in substantia nigra pars compacta with an elevation of N-methyl-d-aspartate receptor (NMDAr) NR2B phosphorylation. The σ1R antagonist NE100 or the NR2B inhibitor Ro25-6981 could alleviate the motor deficits and the death of dopaminergic neurons in MPTP-WT mice. By contrast, MPTP-σ1R+/− mice treated with the σ1R agonist PRE084 or MPTP-σ1R−/− mice treated with the NMDAr agonist NMDA appeared to have similar motor deficits and loss of dopaminergic neurons as MPTP-WT mice. The pharmacological or genetic inactivation of σ1R suppressed the expression of dopamine transporter (DAT) in substantia nigra, which was corrected by NMDA. The activation of σ1R by PRE084 enhanced the DAT expression in WT mice or σ1R+/− mice. By contrast, the level of vesicular monoamine transporter 2 (VMAT2) in σ1R+/− mice or σ1R−/− mice had no difference from WT mice. Interestingly, MPTP-WT mice showed the reduction in the levels of DAT and VMAT2, but MPTP-σ1R−/− mice did not. The inactivation of σ1R by NE100 could prevent the reduction of VMAT2 in MPTP-WT mice. In addition, the activation of microglia cells in substantia nigra was equally enhanced in MPTP-WT mice and MPTP-σ1R−/− mice. The number of activated astrocytes in MPTP-σ1R−/− mice was less than that in MPTP-WT mice. The findings indicate that the σ1R deficiency through suppressing NMDAr function and DAT expression can reduce MPTP-induced death of

  18. 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

  19. 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

  20. 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

  1. 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

  2. Protein profile of Beta vulgaris leaf apoplastic fluid and changes induced by Fe deficiency and Fe resupply.

    PubMed

    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

  3. 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

  4. Soluble epoxide hydrolase deficiency inhibits dextran sulfate sodium-induced colitis and carcinogenesis in mice.

    PubMed

    Zhang, Wanying; Li, Haonan; Dong, Hua; Liao, Jie; Hammock, Bruce D; Yang, Guang-Yu

    2013-12-01

    Soluble epoxide hydrolase (sEH) hydrolyses/inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs) to their corresponding diols, and targeting sEH leads to strong anti-inflammatory effects. In the present study, using a tissue microarray and immunohistochemical approach, a significant increase of sEH expression was identified in ulcerative colitis (UC)-associated dysplasia and adenocarcinoma. The effects of deficiency in the sEH gene were determined on dextran sulfate sodium (DSS) colitis-induced carcinogenesis. The effects of EETs on lipopolysaccharide (LPS)-activated macrophages were analyzed in vitro. With extensive histopathological and immunohistochemical analyses, compared to wild-type mice, sEH(-/-) mice exhibited a significant decrease in tumor incidence (13/20 vs. 6/19, p<0.05) and a markedly reduced average tumor size (59.62±20.91 mm(3) vs. 22.42±11.22 mm(3)), and a significant number of pre-cancerous dysplasia (3±1.18 vs. 2±0.83, p<0.01). The inflammatory activity, as measured by the extent/proportion of erosion/ulceration/dense lymphoplasmacytosis (called active colitis index) in the colon, was significantly lower in sEH(-/-) mice (44.7%±24.9% vs. 20.2%±16.2%, p<0.01). The quantitative polymerase chain reaction (qPCR) assays demonstrated significantly low levels of cytokines/chemokines including monocyte chemoattractant protein (MCP-1), inducible nitric oxide synthase (iNOS), vasopressin-activated calcium-mobilizing (VCAM-1), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). In vitro, LPS-activated macrophages treated with 14,15-EET showed a significant reduction of LPS-triggered IL-1β and TNF-α expression. Eicosanoic acid metabolic profiling revealed a significant increase of the ratios of EETs/ dihydroeicosatrienoic acids (DHETs) and epoxyoctadecennoic acid/dihydroxyoctadecenoic acid (EpOMEs/DiHOMEs). These results indicate that sEH plays an important role in the development of colitis and in inducing carcinogenesis

  5. 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

  6. 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

  7. 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

  8. Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice.

    PubMed

    Wu, Chia-Hua; Mohammadmoradi, Shayan; Thompson, Joel; Su, Wen; Gong, Ming; Nguyen, Genevieve; Yiannikouris, Frédérique

    2016-07-01

    Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR-deficient mice (PRR(Adi/Y)) with almost no detectable white adipose tissues. As a consequence, the livers of PRR(Adi/Y) mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte-PRR-deficient mice were resistant to diet-induced obesity. Both high-fat- and low-fat-fed PRR(Adi/Y) mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRR(Adi/Y) mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRR(Adi/Y) mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRR(Adi/Y) mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARγ (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation. PMID:27185751

  9. Diet-induced iron deficiency anemia and pregnancy outcome in rhesus monkeys12

    PubMed Central

    Golub, Mari S; Hogrefe, Casey E; Tarantal, Alice F; Germann, Stacey L; Beard, John L; Georgieff, Michael K; Calatroni, Agustin; Lozoff, Betsy

    2006-01-01

    Background Iron deficiency anemia (IDA) is relatively common in the third trimester of pregnancy, but causal associations with low birth weight and compromised neonatal iron status are difficult to establish in human populations. Objective The objective was to determine the effects of diet-induced IDA on intrauterine growth and neonatal iron status in an appropriate animal model for third-trimester IDA in women. Design Hematologic and iron-status measures, pregnancy outcomes, and fetal and neonatal evaluations were compared between pregnant rhesus monkeys (n = 14) fed a diet containing 10 μg Fe/g diet from the time of pregnancy detection (gestation days 28–30) and controls (n = 24) fed 100 μg Fe/g diet. Results By the third trimester, 79% of the iron-deprived dams and 29% of the control monkeys had a hemoglobin concentration <11 g/dL. There were also significant group differences in hematocrit, mean corpuscular volume, transferrin saturation, serum ferritin, and serum iron. At birth, the newborns of monkeys iron-deprived during pregnancy had significantly lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin values and a lower ratio of erythroid to total colony-forming units in bone marrow than did the control newborns. Pregnancy weight gain did not differ significantly between the iron-deprived and control dams, and the fetuses and newborns of the iron-deprived dams were not growth retarded relative to the controls. Gestation length, the number of stillbirths, and neonatal neurobehavioral test scores did not differ significantly by diet group. Conclusion These data indicate that an inadequate intake of iron from the diet during pregnancy in rhesus monkeys can lead to compromised hematologic status of the neonate without indications of growth retardation or impaired neurologic function at birth. PMID:16522913

  10. Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury.

    PubMed

    Boddu, Ravindra; Hull, Travis D; Bolisetty, Subhashini; Hu, Xianzhen; Moehle, Mark S; Daher, João Paulo Lima; Kamal, Ahmed Ibrahim; Joseph, Reny; George, James F; Agarwal, Anupam; Curtis, Lisa M; West, Andrew B

    2015-07-15

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson's disease, and LRRK2 is also linked to Crohn's and Hansen's disease. LRRK2 is expressed in many organs in mammals but is particularly abundant in the kidney. We find that LRRK2 protein is predominantly localized to collecting duct cells in the rat kidney, with much lower expression in other kidney cells. While genetic knockout (KO) of LRRK2 expression is well-tolerated in mice and rats, a unique age-dependent pathology develops in the kidney. The cortex and medulla of LRRK2 KO rat kidneys become darkly pigmented in early adulthood, yet aged animals display no overt signs of kidney failure. Accompanying the dark pigment we find substantial macrophage infiltration in LRRK2 KO kidneys, suggesting the presence of chronic inflammation that may predispose to kidney disease. Unexpectedly, the dark kidneys of the LRRK2 KO rats are highly resistant to rhabdomyolysis-induced acute kidney injury compared with wild-type rats. Biochemical profiling of the LRRK2 KO kidneys using immunohistochemistry, proteomic and lipidomic analyses show a massive accumulation of hemoglobin and lipofuscin in renal tubules that account for the pigmentation. The proximal tubules demonstrate a corresponding up-regulation of the cytoprotective protein heme oxygenase-1 (HO-1) which is capable of mitigating acute kidney injury. The unusual kidney pathology of LRRK2 KO rats highlights several novel physiological roles for LRRK2 and provides indirect evidence for HO-1 expression as a protective mechanism in acute kidney injury in LRRK2 deficiency. PMID:25904107

  11. Carnitine Palmitoyltransferase 1b Deficiency Protects Mice from Diet-Induced Insulin Resistance

    PubMed Central

    Kim, Teayoun; He, Lan; Johnson, Maria S.; Li, Yan; Zeng, Ling; Ding, Yishu; Long, Qinqiang; Moore, John F.; Sharer, Jon D.; Nagy, Tim R.; Young, Martin E.; Wood, Philip A.; Yang, Qinglin

    2014-01-01

    Background Carnitine Palmitoyl Transferase 1 (CPT1) is the rate-limiting enzyme governing long-chain fatty acid entry into mitochondria. CPT1 inhibitors have been developed and exhibited beneficial effects against type II diabetes in short-term preclinical animal studies. However, the long-term effects of treatment remain unclear and potential non-specific effects of these CPT1 inhibitors hamper in-depth understanding of the potential molecular mechanisms involved. Methods We investigated the effects of restricting the activity of the muscle isoform CPT1b in mice using heterozygous CPT1b deficient (Cpt1b+/−) and Wild Type (WT) mice fed with a High Fat Diet (HFD) for 22 weeks. Insulin sensitivity was assessed using Glucose Tolerance Test (GTT), insulin tolerance test and hyperinsulinemic euglycemic clamps. We also examined body weight/composition, tissue and systemic metabolism/energetic status, lipid profile, transcript analysis, and changes in insulin signaling pathways. Results We found that Cpt1b+/− mice were protected from HFD-induced insulin resistance compared to WT littermates. Cpt1b+/− mice exhibited elevated whole body glucose disposal rate and skeletal muscle glucose uptake. Furthermore, Cpt1b+/− skeletal muscle showed diminished ex vivo palmitate oxidative capacity by ~40% and augmented glucose oxidation capacity by ~50% without overt change in whole body energy metabolism. HFD feeding Cpt1b+/− but not WT mice exhibited well-maintained insulin signaling in skeletal muscle, heart, and liver. Conclusion The present study on a genetic model of CPT1b restriction supports the concept that partial CPT1b inhibition is a potential therapeutic strategy. PMID:25309812

  12. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells

    PubMed Central

    Yusa, Kosuke; Rashid, S. Tamir; Strick-Marchand, Helene; Varela, Ignacio; Liu, Pei-Qi; Paschon, David E.; Miranda, Elena; Ordóñez, Adriana; Hannan, Nick; Rouhani, Foad Jafari; Darche, Sylvie; Alexander, Graeme; Marciniak, Stefan J.; Fusaki, Noemi; Hasegawa, Mamoru; Holmes, Michael C.; Di Santo, James P.; Lomas, David A.; Bradley, Allan; Vallier, Ludovic

    2011-01-01

    Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders1,2,3,4. However, the use of hIPSCs in the context of genetically inherited human disease will require correction of disease-causing mutations in a manner that is fully compatible with clinical applications3,5. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome6. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of hIPSCs. Here, we show that a combination of zinc finger nucleases (ZFNs)7 and piggyBac8,9 technology in hIPSCs can achieve bi-allelic correction of a point mutation (Glu342Lys) in the α1-antitrypsin (A1AT, also called SERPINA1) gene that is responsible for α1-antitrypsin deficiency (A1ATD). Genetic correction of hIPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle for the potential of combining hIPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies. PMID:21993621

  13. Epidemiology of nodular goitre. Influence of iodine intake.

    PubMed

    Carlé, Allan; Krejbjerg, Anne; Laurberg, Peter

    2014-08-01

    More than one tenth of the world population is to some degree affected by goitre and most of these harbour nodules. The large differences in thyroid disease prevalence between populations may be caused by genetic and environmental factors. Among the latter, iodine deficiency seems by far to be the most important risk factor. Thus, nodular goitre is a condition predominantly seen in iodine deficient areas of the world. In the present review, we evaluated in detail autopsy and ultrasound studies of the thyroid gland. In autopsy studies, large thyroid volumes and high frequencies of goitres have been reported in countries affected by iodine deficiency. Many cross-sectional studies using thyroid ultrasound investigations have been performed world-wide and reported high thyroid volumes and goitre prevalences, and to some extent also high prevalences of thyroid nodules in iodine-deficient countries. Most of these goitres were classified as nodular goitres. On the other hand, few studies have shown that abundant iodine intake may lead to development of diffuse goitres, but world-wide this has been a minor problem compared with development of nodular goitres. In the past century we have observed a trend towards smaller thyroid glands, and hopefully less than 10% of the world population will experience goitre within a few decades. PMID:25047199

  14. Attenuation of high sucrose diet–induced insulin resistance in tryptophan 2,3-dioxygenase deficient Drosophila melanogaster vermilion mutants

    PubMed Central

    Navrotskaya, Valeriya; Oxenkrug, Gregory; Vorobyova, Lyudmila; Summergrad, Paul

    2015-01-01

    Exposure to high sugar diet (HSD) serves as an experimental model of insulin resistance (IR) and type 2 diabetes (T2D) in mammals and insects. Peripheral IR induced by HSD delays emergence of pupae from larvae and decreases body weight of Drosophila imago. Understanding of mechanisms of IR/T2D is essential for refining T2D prevention and treatment strategies. Dysregulation of tryptophan (TRP) – kynurenine (KYN) pathway was suggested as one of the mechanisms of IR development. Rate-limiting enzyme of TRP – KYN pathway in Drosophila is TRP 2,3-dioxygenase (TDO), an evolutionary conserved ortholog of human TDO. In insects TDO is encoded by vermilion gene. TDO is not active in vermilion mutants. In order to evaluate the possible impact of deficient formation of KYN from TRP on the inducement of IR by HSD, we compared the effect of HSD in wild type (Oregon) and vermilion mutants of Drosophila melanogaster by assessing the time of white pupae emergence from larva and body weight of imago. Delay of emergence of pupae from larvae induced by high sucrose diet was less pronounced in vermilion (1.4 days) than in Oregon flies (3.3 days) in comparison with flies maintained on standard diet. Exposure to high sucrose diet decreased body weight of Oregon (but not vermilion) imago. Attenuation of high sucrose diet–induced IR/T2D in vermilion flies might depend on deficiency of TRP – KYN pathway. Besides IR/T2D, HSD induces obesity in Drosophila. Future studies of HSD-induced obesity and IR/T2D in TDO deficient vermilion mutants of Drosophila might help to understand the mechanisms of high association between IR/T2D and obesity. Modulation of TRP – KYN metabolism might be utilized for prevention and treatment of IR/T2D. PMID:26191458

  15. Dietary zinc deficiency induces oxidative stress and promotes tumor necrosis factor-α- and interleukin-1β-induced RANKL expression in rat bone

    PubMed Central

    Suzuki, Takako; Katsumata, Shin-ichi; Matsuzaki, Hiroshi; Suzuki, Kazuharu

    2016-01-01

    We investigated the effects of dietary zinc deficiency on oxidative stress and bone metabolism. Four-week-old male Wistar rats were randomly assigned to one of three groups for 4 weeks: a zinc-adequate group (30 ppm); a zinc-deficient group (1 ppm); and a pair-fed group (30 ppm) that was pair-fed to the zinc-deficient group. The iron content and the thiobarbituric acid reactive substance level in bone were higher in the zinc-deficient group than in the zinc-adequate and pair-fed groups. The mRNA expression level of osteoblastogenesis-related genes such as bone morphogenetic protein 2 and runt-related transcription factor 2 was lower in the zinc-deficient group than in the zinc-adequate and pair-fed groups. In contrast, the mRNA expression levels of tumor necrosis factor-α, interleukin-1β and osteoclastogenesis-related genes such as receptor activator of nuclear factor-κB ligand and nuclear factor of activated T cells cytoplasmic 1 were higher in the zinc-deficient group than in the zinc-adequate and pair-fed groups. These findings suggested that dietary zinc deficiency reduced osteoblastogenesis via a decrease in the expression of bone morphogenetic protein 2 and increased osteoclastogenesis via enhancement of the expression of receptor for activator of nuclear factor-κB ligand induced by oxidative stress-stimulated tumor necrosis factor-α and interleukin-1β. PMID:27013778

  16. Diquat induces renal proximal tubule injury in glutathione reductase-deficient mice

    SciTech Connect

    Rogers, Lynette K. . E-mail: rogersl@ccri.net; Bates, Carlton M.; Welty, Stephen E.; Smith, Charles V.

    2006-12-15

    Reactive oxygen species (ROS) have been associated with many human diseases, and glutathione (GSH)-dependent processes are pivotal in limiting tissue damage. To test the hypothesis that Gr1{sup a1Neu} (Neu) mice, which do not express glutathione reductase (GR), would be more susceptible than are wild-type mice to ROS-mediated injury, we studied the effects of diquat, a redox cycling toxicant. Neu mice exhibited modest, dose- and time-dependent elevations in plasma alanine aminotransferase (ALT) activities, 126 {+-} 36 U/l at 2 h after 5 {mu}mol/kg of diquat, but no ALT elevations were observed in diquat-treated C3H/HeN mice for up to 6 h after 50 {mu}mol/kg of diquat. Histology indicated little or no hepatic necrosis in diquat-treated mice of either strain, but substantial renal injury was observed in diquat-treated Neu mice, characterized by brush border sloughing in the proximal tubules by 1 h and tubular necrosis by 2 h after doses of 7.5 {mu}mol/kg. Decreases in renal GSH levels were observed in the Neu mice by 2 h post dose (3.4 {+-} 0.4 vs 0.2 {+-} 0.0 {mu}mol/g tissue at 0 and 50 {mu}mol/kg, respectively), and increases in renal GSSG levels were observed in the Neu mice as early as 0.5 h after 7.5 {mu}mol/kg (105.5 {+-} 44.1 vs 27.9 {+-} 4.8 nmol/g tissue). Blood urea nitrogen levels were elevated by 2 h in Neu mice after doses of 7.5 {mu}mol/kg (Neu vs C3H, 32.8 {+-} 4.1 vs 17.9 {+-} 0.3 mg/dl). Diquat-induced renal injury in the GR-deficient Neu mice offers a useful model for studies of ROS-induced renal necrosis and of the contributions of GR in defense against oxidant-mediated injuries in vivo.

  17. GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus

    PubMed Central

    Yu, Hong; Vikhe Patil, Kim; Han, Chul; Fabella, Brian; Canlon, Barbara; Someya, Shinichi; Cederroth, Christopher R.

    2016-01-01

    Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the

  18. GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus.

    PubMed

    Yu, Hong; Vikhe Patil, Kim; Han, Chul; Fabella, Brian; Canlon, Barbara; Someya, Shinichi; Cederroth, Christopher R

    2016-01-01

    Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the

  19. Generation of CD44 gene-deficient mouse derived induced pluripotent stem cells: CD44 gene-deficient iPSCs.

    PubMed

    Song, Zhenwei; Ji, Qianqian; Zhao, Haijing; Nie, Yu; He, Zuyong; Chen, Yaosheng; Cong, Peiqing

    2014-10-01

    Induced pluripotent stem cells (iPSCs) show good promise for the treatment of defects caused by numerous genetic diseases. Herein, we successfully generated CD44 gene-deficient iPSCs using Oct4, Sox2, Klf4, and vitamin C. The generated iPSCs displayed a characteristic morphology similar to the well-characterized embryonic stem cells. Alkaline phosphatase, cell surface (SSEA1, NANOG, and OCT4), and pluripotency markers were expressed at high levels in these cells. The iPSCs formed teratomas in vivo and supported full-term development of constructed porcine embryos by inter-species nuclear transplantation. Importantly, incubation with trichostatin A increased the efficiency of iPSCs generation by increasing the histone acetylation levels. Moreover, more iPSCs colonies appeared following cell passaging during colony picking, thus increasing the effectiveness of iPSCs selection. Thus, our work provides essential stem cell materials for the treatment of genetic diseases and proposes a novel strategy to enhance the efficiency of induced reprogramming. PMID:24952030

  20. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model

    PubMed Central

    Martínez-Morentin, Leticia; Martínez, Lidia; Piloto, Sarah; Yang, Hua; Schon, Eric A.; Garesse, Rafael; Bodmer, Rolf; Ocorr, Karen; Cervera, Margarita; Arredondo, Juan J.

    2015-01-01

    The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans. PMID:25792727

  1. Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator

    PubMed Central

    de Giorgio-Miller, Alexander; Bottoms, Steve; Laurent, Geoffrey; Carmeliet, Peter; Herrick, Sarah

    2005-01-01

    The deposition of fibrin is an integral part of the tissue repair process, but its persistence is also associated with a number of fibrotic conditions. This study addressed the hypothesis that reduced fibrinolysis and fibrin persistence are associated with an enhanced accumulation of collagen and the development of skin fibrosis. Decreased fibrinolysis was confirmed in fibrin gel cultures that contained human dermal fibroblasts plus the specific plasmin inhibitor α2-antiplasmin or dermal fibroblasts isolated from plasminogen activator (PA)-deficient mice. Collagen accumulation was significantly increased in the presence of inhibitor and in tPA-deficient, but not uPA-deficient, fibroblasts compared with controls. These findings were also confirmed using a skin fibrosis model in which multiple injections of fibrin were given subcutaneously to PA-deficient mice. Injection sites from tPA-deficient mice displayed significantly increased collagen levels compared with uPA-deficient mice and wild-type controls. Up-regulation of fibroblast procollagen gene expression and reduced activation of pro-MMP-1 appeared to mediate the increase in collagen by human dermal fibroblasts in the presence of α2-antiplasmin. These findings suggest that persistent fibrin is associated with enhanced collagen accumulation that may result in the development of fibrotic skin disorders in which reduced fibrinolysis is a feature. PMID:16127152

  2. 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.

  3. A deficiency in Mdm2 binding protein (MTBP) inhibits Myc-induced B cell proliferation and lymphomagenesis

    PubMed Central

    Odvody, Jessica; Vincent, Tiffaney; Arrate, Maria Pia; Grieb, Brian; Wang, Shuo; Garriga, Judit; Lozano, Guillermina; Iwakuma, Tomoo; Haines, Dale S.; Eischen, Christine M.

    2010-01-01

    Mdm2 binding protein (MTBP) has been implicated in cell cycle arrest and the Mdm2-p53 tumor suppressor pathway through its interaction with Mdm2. To determine the function of MTBP in tumorigenesis and its potential role in the Mdm2-p53 pathway, we crossed Mtbp deficient mice to Eµ-myc transgenic mice, in which overexpression of the oncogene c-Myc induces B cell lymphomas primarily through inactivation of the Mdm2-p53 pathway. We report that Myc-induced B cell lymphoma development in Mtbp heterozygous mice was profoundly delayed. Surprisingly, reduced levels of Mtbp did not lead to an increase in B cell apoptosis or affect Mdm2. Instead, an Mtbp deficiency inhibited Myc-induced proliferation and the upregulation of Myc target genes necessary for cell growth. Consistent with a role in proliferation, Mtbp expression was induced by Myc and other factors that promote cell cycle progression and was elevated in lymphomas from humans and mice. Therefore, Mtbp functioned independent of Mdm2 and was a limiting factor for the proliferative and transforming functions of Myc. Thus, Mtbp is a previously unrecognized regulator of Myc-induced tumorigenesis. PMID:20305689

  4. 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. PMID:26631051

  5. Nitric Oxide Deficiency Accelerates Chlorophyll Breakdown and Stability Loss of Thylakoid Membranes during Dark-Induced Leaf Senescence in Arabidopsis

    PubMed Central

    Liu, Fang; Guo, Fang-Qing

    2013-01-01

    Nitric oxide (NO) has been known to preserve the level of chlorophyll (Chl) during leaf senescence. However, the mechanism by which NO regulates Chl breakdown remains unknown. Here we report that NO negatively regulates the activities of Chl catabolic enzymes during dark-induced leaf senescence. The transcriptional levels of the major enzyme genes involving Chl breakdown pathway except for RED CHL CATABOLITE REDUCTASE (RCCR) were dramatically up-regulated during dark-induced Chl degradation in the leaves of Arabidopsis NO-deficient mutant nos1/noa1 that exhibited an early-senescence phenotype. The activity of pheide a oxygenase (PAO) was higher in the dark-induced senescent leaves of nos1/noa1 compared with wild type. Furthermore, the knockout of PAO in nos1/noa1 background led to pheide a accumulation in the double mutant pao1 nos1/noa1, which retained the level of Chl during dark-induced leaf senescence. The accumulated pheide a in darkened leaves of pao1 nos1/noa1 was likely to inhibit the senescence-activated transcriptional levels of Chl catabolic genes as a feed-back inhibitory effect. We also found that NO deficiency led to decrease in the stability of photosynthetic complexes in thylakoid membranes. Importantly, the accumulation of pheide a caused by PAO mutations in combination with NO deficiency had a synergistic effect on the stability loss of thylakoid membrane complexes in the double mutant pao1 nos1/noa1 during dark-induced leaf senescence. Taken together, our findings have demonstrated that NO is a novel negative regulator of Chl catabolic pathway and positively functions in maintaining the stability of thylakoid membranes during leaf senescence. PMID:23418559

  6. Galanin 3 receptor-deficient mice show no alteration in the oxazolone-induced contact dermatitis phenotype.

    PubMed

    Botz, Bálint; Brunner, Susanne M; Kemény, Ágnes; Pintér, Erika; McDougall, Jason J; Kofler, Barbara; Helyes, Zsuzsanna

    2016-09-01

    Allergic contact dermatitis (ACD) is an inflammatory skin disease induced by allergen exposure and characterized by erythema, oedema and immune cell infiltration. The sensory peptide galanin (GAL) and its three receptors (GAL1-3 ) are involved in regulating inflammation. As GAL and its receptors are expressed in human and murine skin and GAL expression is increased in oxazolone-induced contact allergy, it could play a role in dermatitis. As GAL reduces neurogenic plasma extravasation in the mouse skin via GAL3 activation, the role of GAL3 in the oxazolone-induced dermatitis model was explored. Following topical challenge with oxazolone, GAL3 gene-deficient mice showed a trend towards reduced ear thickness. Plasma extravasation and neutrophil infiltration increased considerably upon oxazolone challenge in both GAL3 knockout animals and wild-type controls without any observable effect of the gene deletion. We conclude that a lack of GAL3 does not influence oxazolone-induced ACD. PMID:27121264

  7. Goiter Frequency Is More Strongly Associated with Gastric Adenocarcinoma than Urine Iodine Level

    PubMed Central

    Tabaeizadeh, Mohammad; Haghpanah, Vahid; Keshtkar, Abbasali; Semnani, Shahryar; Roshandel, Gholamreza; Adabi, Khadijeh; Heshmat, Ramin; Rohani, Davood; Kia, Alireza; Hatami, Ehsan; Jahangirrad, Ataollah; Nabizadeh, Ramin

    2013-01-01

    Purpose We designed our study to evaluate the hypothesis that gastric cancer is correlated with iodine deficiency or thyroid dysfunction. Materials and Methods We investigated the total body iodine reserve, thyroid function status and autoimmune disorder in 40 recently diagnosed gastric adenocarcinoma cases versus 80 healthy controls. The participants came from a region with high gastric cancer rate but sufficient iodine supply due to salt iodination. The investigation included urine iodine level, thyroid gland clinical and ultrasonographic examination, and thyroid function tests. Results Goiter was detected more frequently in the case group (P=0.001); such a finding, however, was not true for lower than normal urine iodine levels. The free T3 mean level was significantly lower in the case group compared to the control group (P=0.005). Conclusions The higher prevalence of goiter rather than low levels of urinary iodine in gastric adenocarcinoma cases suggests that goiter, perhaps due to protracted but currently adjusted iodine deficiency, is more likely to be associ