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Sample records for iodine deficiency induces

  1. The disorders induced by iodine deficiency.

    PubMed

    Delange, F

    1994-01-01

    This paper reviews present knowledge on the etiology, pathophysiology, complications, prevention, and therapy of the disorders induced by iodine deficiency. The recommended dietary allowances of iodine are 100 micrograms/day for adults and adolescents, 60-100 micrograms/day for children aged 1 to 10 years, and 35-40 micrograms/day in infants aged less than 1 year. When the physiological requirements of iodine are not met in a given population, a series of functional and developmental abnormalities occur including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retardation, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute a hindrance to the development of the affected populations, are grouped under the general heading of iodine deficiency disorders (IDD). At least one billion people are at risk of IDD. Iodine deficiency, therefore, constitutes one of the most common preventable causes of mental deficiency in the world today. Most of the affected populations live in mountainous areas in preindustrialized countries, but 50 to 100 million people are still at risk in Europe. The most important target groups to the effects of iodine deficiency from a public health point of view are pregnant mothers, fetuses, neonates, and young infants because the main complication of IDD, i.e., brain damage resulting in irreversible mental retardation, is the consequence of thyroid failure occurring during pregnancy, fetal, and early postnatal life. The main cause of endemic goiter and cretinism is an insufficient dietary supply of iodine. The additional role of naturally occurring goitrogens has been documented in the case of certain foods (milk, cassava, millet, nuts) and bacterial and chemical water pollutants. The mechanism by which the thyroid gland adapts to an insufficient iodine supply is to increase the trapping of iodide as well as the subsequent

  2. Epidemiology of iodine deficiency.

    PubMed

    Vanderpump, Mark P

    2017-04-01

    Iodine is an essential component of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) produced by the thyroid gland. Iodine deficiency impairs thyroid hormone production and has adverse effects throughout life, particularly early in life as it impairs cognition and growth. Iodine deficiency remains a significant problem despite major national and international efforts to increase iodine intake, primarily through the voluntary or mandatory iodization of salt. Recent epidemiological data suggest that iodine deficiency is an emerging issue in industrialized countries, previously thought of as iodine-sufficient. International efforts to control iodine deficiency are slowing, and reaching the third of the worldwide population that remains deficient poses major challenges.

  3. 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 ...

  4. Iodine deficiency: Clinical implications.

    PubMed

    Niwattisaiwong, Soamsiri; Burman, Kenneth D; Li-Ng, Melissa

    2017-03-01

    Iodine is crucial for thyroid hormone synthesis and fetal neurodevelopment. Major dietary sources of iodine in the United States are dairy products and iodized salt. Potential consequences of iodine deficiency are goiter, hypothyroidism, cretinism, and impaired cognitive development. Although iodine status in the United States is considered sufficient at the population level, intake varies widely across the population, and the percentage of women of childbearing age with iodine deficiency is increasing. Physicians should be aware of the risks of iodine deficiency and the indications for iodine supplementation, especially in women who are pregnant or lactating.

  5. 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.

  6. 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.

  7. Iodine deficiency in Europe.

    PubMed

    Delange, F

    1995-01-18

    Iodine is a trace element present in the human body in minute amounts (15-20 mg in adults, i.e. 0.0285 x 10(-3)% of body weight). The only confirmed function of iodine is to constitute an essential substrate for the synthesis of thyroid hormones, tetraiodothyronine, thyroxine or T4 and triiodothyronine, T3 (1). In thyroxine, iodine is 60% by weight. Thyroid hormones, in turn, play a decisive role in the metabolism of all cells of the organism (2) and in the process of early growth and development of most organs, especially of the brain (3). Brain development in humans occurs from fetal life up to the third postnatal year (4). Consequently, a deficit in iodine and/or in thyroid hormones occurring during this critical period of life will result not only in the slowing down of the metabolic activities of all the cells of the organism but also in irreversible alterations in the development of the brain. The clinical consequence will be mental retardation (5). When the physiological requirements of iodine are not met in a given population, a series of functional and developmental abnormalities occur (Table 1), including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retardation, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute an hindrance to the development of the affected population, are grouped under the general heading of Iodine Deficiency Disorders, IDD (6). Broad geographic areas exist in which the population is affected by IDD.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 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

  9. MARGINAL IODINE DEFICIENCY EXACERBATES PERCHLORATE THYROID TOXICITY.

    EPA Science Inventory

    The environmental contaminant perchlorate disrupts thyroid homeostasis via inhibition of iodine uptake into the thyroid. This work tested whether iodine deficiency exacerbates the effects of perchlorate. Female 27 day-old LE rats were fed a custom iodine deficient diet with 0, 50...

  10. Dietary restriction causing iodine-deficient goitre.

    PubMed

    Cheetham, Tim; Plumb, Emma; Callaghan, James; Jackson, Michael; Michaelis, Louise

    2015-08-01

    Iodine-deficient goitre was common in some parts of the UK prior to the introduction of salt iodisation. Many contemporary salt preparations do not contain much iodine, and there are renewed concerns about the iodine status of the population. We present a boy with severe allergy who developed goitre and significant thyroid dysfunction in association with an iodine-deficient 'food-restricted' diet. The case highlights the importance of a comprehensive nutritional assessment in all children on multiple food restrictions.

  11. Iodine deficiency, more than cretinism and goiter.

    PubMed

    Verheesen, R H; Schweitzer, C M

    2008-11-01

    Recent reports of the World Health Organization show iodine deficiency to be a worldwide occurring health problem. As iodine status is based on median urinary iodine excretion, even in countries regarded as iodine sufficient, a considerable part of the population may be iodine deficient. Iodine is a key element in the synthesis of thyroid hormones and as a consequence, severe iodine deficiency results in hypothyroidism, goiter, and cretinism with the well known biochemical alterations. However, it is also known that iodine deficiency may give rise to clinical symptoms of hypothyroidism without abnormality of thyroid hormone values. This led us to the hypothesis that iodine deficiency may give rise to subtle impairment of thyroid function leading to clinical syndromes resembling hypothyroidism or diseases that have been associated with the occurrence of hypothyroidism. We describe several clinical conditions possibly linked to iodine deficiency, a connection that has not been made thus far. In this paper we will focus on the relationship between iodine deficiency and obesity, attention deficit hyperactivity disorder (ADHD), psychiatric disorders, fibromyalgia, and malignancies.

  12. 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.

  13. Historical aspects of iodine deficiency control.

    PubMed

    Vanderpas, Jean-Baptiste; Moreno-Reyes, Rodrigo

    2017-04-01

    In 1895, iodine was characterized as an essential element of thyroid tissue by Baumann. The efficacy of iodine to prevent goiter was demonstrated by Marine in Northern USA in 1916-1920. Severe endemic goiter and cretinism had been almost entirely eliminated from continental Western Europe and Northern America before the 1930's; however large populations elsewhere and even some places in Western Europe (Sicily) were still affected up to the 2000's. Public health consequences of iodine deficiency are not limited to endemic goiter and cretinism. Iodine deficiency disorders include also increased neonatal death rate and decreased intellectual development, although these consequences are not included in the current estimation of the Global Burden Disease related to iodine deficiency. Severe iodine deficiency as a public health problem is now largely under control worldwide, but can still affect isolated places, in hard-to-reach and/or politically neglected populations. We emphasize the importance of maintaining international cooperation efforts, in order to monitor iodine status where iodine deficiency is now adequately controlled, and identify at-risk population where it is not. The goal should be now global eradication of severe iodine deficiency. Commercial distribution of iodized salt remains the most appropriate strategy. A randomized clinical trial in New Guinea clearly showed in the 1970's that correcting severe iodine deficiency early in pregnancy prevents endemic neurological cretinism. This supports the essential role of thyroid hormones of maternal origin on the normal fetal development, during the first trimester of pregnancy (i.e. when fetal thyroid is still not functional). A randomized clinical trial in Congo (RD) in the 1970's also showed that correcting severe iodine deficiency during pregnancy prevents myxœdematous cretinism, particularly prevalent in affected Congolese areas.

  14. Promotion of N-methyl-N-nitrosourea-induced thyroid tumors by iodine deficiency in F344/NCr rats.

    PubMed

    Ohshima, M; Ward, J M

    1984-07-01

    Six-week-old male F344 rats were each given an injection once iv of N-methyl-N-nitrosourea [(MNU) CAS: 684-93-5] at a dose of 41.2 mg/kg body weight. Two weeks later, groups of rats were placed on iodine-deficient (ID) or iodine-adequate (IA) diets and then sacrificed at 20 and 33 weeks. Other groups received ID or IA diets without MNU. For localizing thyroid-stimulating hormone (TSH) and prolactin, sections of pituitary glands were stained by the avidin-biotin-peroxidase complex technique with the use of anti-rat TSH or prolactin antibody. At 20 weeks, rats receiving MNU and ID diets had a 100% incidence of diffuse follicular goiter and multiple follicular adenomas of the thyroid. Focal proliferative thyroid follicular lesions including focal hyperplasias and adenomas per square centimeter of thyroid gland were significantly increased in rats given MNU and ID diets in comparison with rats given MNU and IA diets. At 33 weeks, all MNU rats on ID diets had a significantly increased incidence of thyroid carcinoma of the follicular or papillary types and diffuse pituitary thyrotroph hyperplasia, hypertrophy, and vacuolar degeneration. Rats fed ID diets without MNU had diffuse follicular goiter but no tumors at any time period. MNU given alone in rats fed IA diets induced a 10% incidence of single thyroid adenomas at 20 weeks and 70% at 33 weeks and a 10% incidence of thyroid carcinoma at 33 weeks. Tumors induced in other organs by MNU were not affected by the ID diets. Thus this experiment provided evidence that ID diets are potent promoters of thyroid tumors in this system, but the ID diet itself without carcinogen was not carcinogenic under the conditions of the study.

  15. 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.

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

    PubMed

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

    2014-02-01

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

  17. 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

  18. Severe Hypothyroidism From Iodine Deficiency Associated With Parenteral Nutrition.

    PubMed

    Golekoh, Marjorie C; Cole, Conrad R; Jones, Nana-Hawa Yayah

    2016-11-01

    Parenteral nutrition is crucial for supply of nutrients in children who cannot tolerate a full enteral diet. In the United States, it is not standard of care to give iodine to children dependent on parenteral nutrition, hence iodine is not routinely included in the micronutrient package. Herein, we present a case of a boy with hypothyroidism secondary to iodine deficiency after prolonged exclusive use of parenteral nutrition. Our case highlights the importance of screening for iodine deficiency and administering timely iodine supplementation in these at-risk children to prevent iatrogenic hypothyroidism.

  19. 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…

  20. Current Iodine Nutrition Status and Awareness of Iodine Deficiency in Tuguegarao, Philippines

    PubMed Central

    Kim, Bu Kyung; Seok, Kwang-Hyuk; Lee, Andrew S.; Oak, Chul Ho; Kim, Ghi Chan; Jeong, Chae-Kyeong; Choi, Sung In; Afidchao, Pablo M.; Choi, Young Sik

    2014-01-01

    The Philippines is one of the countries where adequate iodine status has been achieved. However, iodine deficiency still remains an important public health problem in this country. In this study, we evaluated iodine nutrition status and investigated an awareness status of iodine deficiency targeting high school students of Tuguegarao, Philippines. A total of 260 students provided samples for urinary iodine analysis, among which 146 students completed thyroid volume measurement by ultrasonography and answering the questionnaires. The median urinary iodine level was 355.3 µg/L and only 3.8% of the students were in the range of iodine deficiency status according to the ICCIDD criteria. Although 62.3% of students answered that they can list problems resulting from iodine deficiency, a majority of students (70.5%) were unable to identify problems other than goiter. They did not appreciate that adequate iodine levels are important during pregnancy and for development of children. 33.6% of students answered that they did not use iodized salt and the biggest reason was that they did not find it necessary. Based on these results, we suggest that a future strategy should be focused on vulnerable groups to completely eliminate iodine deficiency, including women at their reproductive ages and during pregnancy. PMID:25374598

  1. 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

  2. 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.

  3. [Sanitary and technological solutions of the elimination of iodine deficiency by iodination of drinking water].

    PubMed

    Rakhmanin, Iu A; Kir'ianova, L F; Mikhaĭlova, R I; Sevost'ianova, E M; Ryzhova, I N; Alekseeva, A B; Nedachin, A E

    2001-01-01

    Comprehensive studies of the sanitary standards provided research evidence for the maximum allowable concentrations of iodine in the drinking water by taking into account its daily allowances dose and the formation of transformation by-products due to iodine disinfection, drinking water preservation, and iodine deficiency prevention in the endemic areas. Techniques of water iodination have been devised and tested in the experimental and industrial setting, including those for packaging drinking water, as well as those by using portable water purifiers based on highly effective iodine-selective adsorptive compounds which make it possible to solve the task of administering iodine dosages into the water (with allowances born in mind), under domestic conditions as well.

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

    PubMed

    Caron, Philippe

    2015-07-01

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

  5. Combating iodine deficiency: lessons from China, Indonesia, and Madagascar.

    PubMed

    Goh, Chor-ching

    2002-09-01

    This study investigated the factors contributing to a successful and sustainable elimination of iodine-deficiency disorders, drawing from salt fortification experiences in China, Indonesia, and Madagascar. Government officials, salt farmers, salt producers, and wholesalers were interviewed to collect data during field visits. Analyses used in the study include simple correlation, and wherever data permit, regression. The study found that measures crucial for combating iodine deficiency include raising public awareness of the disorders, ensuring easy access to iodated salt, promoting compliance in the salt industry, and monitoring and enforcement. Factors that ensure a reliable supply of iodated salt are equally important as those that create the demand for it. Governments must ensure that surveillance and enforcement mechanisms are functioning right from the time that salt iodation is made compulsory. For sustainability during later years, the adequacy of iodine in iodated salt must be monitored, and incentives must be modified as needed to increase compliance rates in the salt industry. Once national coverage of iodated salt reaches over 90%, the government can concentrate on fine-tuning and targeting resources at areas with a low consumption of iodated salt. Elimination of micronutrient deficiencies has a long-term impact on public health; moreover, poorer segments of the population, who are more vulnerable to such deficiencies, have more to gain from fortification programs. Thus, lessons from the successful elimination of iodine-deficiency disorders are valuable for future similar micronutrient activities.

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

    PubMed

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

    2012-01-01

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

  7. 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…

  8. [Iodine deficiency in the world and in the Czech Republic--current status and perspectives].

    PubMed

    Zamrazil, V; Bílek, R; Cerovská, J; Dvoráková, M; Nemecek, J

    2010-12-01

    Iodopenia is importance world-wide problem--the cause of spectrum of iodine deficiency disorders (IDD). The "simple" way for its compensation is iodine supplementation--preferably by iodinization of salt: in the Czech Republic prevalence of IDD was very high in the past. The complex program for compensation of iodine deficiency realized in the CR includes improvement of salt iodization, supplementation of pregnant and lactating women, fortification of products for babies' nutrition and increasing use of iodinized salt in general population incl. food industry. Thus CR is country with compensated iodine deficiency according to criteria WHO, UNICEF, ICCIDD. In future, however, systematic interest should be focused on optimalization of iodine saturation, esp. in pregnant women and evaluation of possible risk of supranormal iodine intake (impairment of thyroid function, activation of thyroid autoimmunity). Taking in account, the changes of nutrition and life style systematic monitoring of quality of iodine supplementation seems to be essential.

  9. 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.

  10. Iodine deficiency in the U.K.: an overlooked cause of impaired neurodevelopment?

    PubMed

    Bath, Sarah C; Rayman, Margaret P

    2013-05-01

    This review describes historical iodine deficiency in the U.K., gives current information on dietary sources of iodine and summarises recent evidence of iodine deficiency and its association with child neurodevelopment. Iodine is required for the production of thyroid hormones that are needed for brain development, particularly during pregnancy. Iodine deficiency is a leading cause of preventable brain damage worldwide and is associated with impaired cognitive function. Despite a global focus on the elimination of iodine deficiency, iodine is a largely overlooked nutrient in the U.K., a situation we have endeavoured to address through a series of studies. Although the U.K. has been considered iodine-sufficient for many years, there is now concern that iodine deficiency may be prevalent, particularly in pregnant women and women of childbearing age; indeed we found mild-to-moderate iodine deficiency in pregnant women in Surrey. As the major dietary source of iodine in the U.K. is milk and dairy produce, it is relevant to note that we have found the iodine concentration of organic milk to be over 40% lower than that of conventional milk. In contrast to many countries, iodised table salt is unlikely to contribute to U.K. iodine intake as we have shown that its availability is low in grocery stores. This situation is of concern as the level of U.K. iodine deficiency is such that it is associated with adverse effects on offspring neurological development; we demonstrated a higher risk of low IQ and poorer reading-accuracy scores in U.K. children born to mothers who were iodine-deficient during pregnancy. Given our findings and those of others, iodine status in the U.K. population should be monitored, particularly in vulnerable subgroups such as pregnant women and children.

  11. Iodine, copper, zinc, selenium and molybdenum levels in children aged between 6 and 12 years in the rural area with iodine deficiency and in the city center without iodine deficiency in Hatay

    PubMed Central

    Çelik, Tanju; Savaş, Nazan; Kurtoğlu, Selim; Sangün, Özlem; Aydın, Zeki; Mustafa, Didin; Öztürk, Oktay Hasan; Mısırlıoğlu, Seher; Öktem, Murat

    2014-01-01

    Aim: Thyroid diseases related with iodine deficiency are observed commonly in our country and in the world. In this study, we aimed to investigate iodine deficiency in urine and selenium, zinc, copper or molybdenum deficiency which may accompany this in children aged between 6 and 12 years in two schools in the province of Hatay (endemic goitre region). Material and Methods: This study is a case-control field-study in which students aged between 6 and 12 years were included. One hundred fourteen subjects from the village of Tanışma related to the center of our province and 100 subjects from the city center of Hatay (Antakya) were included in the study. Iodine, selenium, zinc, copper and molybdenum levels were measured in the urine samples of the students included in the study. Results: Iodine deficiency was found with a severe (5%), moderate (18.4%) and mild degree (43%), respectively in the village of Tanışma. Mild iodine deficiency (7%) was found in the center of Hatay. No moderate and severe iodine deficiency was found in the control group. A significant difference was found between the groups in terms of urine iodine excretion (p<0.001). A significant correlation was found between the levels of iodine, selenium, zinc and molybdenum (p<0.05). A moderately positive correlation was found between iodine and selenium (p<0.001). A moderately positive correlation was found between iodine and zinc levels (p<0.001) and a weak correlation was found between iodine and molybdenum (p<0.01). No significant correlation was found between iodine level and copper level (p>0.05). Conclusions: Selenium and zinc deficiency may accompany iodine deficiency. Selenium and zinc deficiency should be considered in individuals who are found to have iodine deficiency especially in endemic goitre regions. PMID:26078645

  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.

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

    PubMed

    Doggui, Radhouene; El Atia, Jalila

    2015-02-01

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

  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.

  15. 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.

  16. 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

  17. 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.

  18. Factors affecting sustainable iodine deficiency elimination in Pakistan: A global perspective.

    PubMed

    Khattak, Rehman Mehmood; Khattak, Muhammad Nasir Khan; Ittermann, Till; Völzke, Henry

    2017-02-16

    Iodine deficiency remains a considerable challenge worldwide, even after decades of efforts to address the problem. The aim of this review is to present the current situation in historically iodine-deficient Pakistan regarding iodine nutritional status and place it in a global perspective. We collected relevant articles from online bibliographic databases and websites of concerned organizations that addressed prevalence of goiter/iodine deficiency and barriers to sustainable control. We divided the studies into pre- and post-1994, a landmark year when Pakistan formally adopted the universal salt iodization (USI) programme. Overall, 56 studies reported goiter/iodine deficiency prevalence in Pakistan. Before 1994, six studies (30%) reported a goiter prevalence ≥70%, while nine studies (45%) reported a goiter prevalence between 30% and 70%. Only five studies (25%) found a goiter prevalence less than 30%, of which only two studies reported prevalence <10%. From 1994 onwards, 15 studies (41.7%) reported a goiter/iodine deficiency (ID) prevalence ≥50%, of which seven studies reported prevalence ≥70%, while three studies (8.3%) found a goiter prevalence of 30%-49%, nine studies (25%) found a goiter prevalence of 10%-29%, and five studies (13.9%) reported prevalence of <10%. Four studies (11.1%) reported lower goiter prevalence but higher prevalence of iodine deficiency. The efforts in the past two decades resulted in up to a 50% decline in iodine deficiency disorders (IDD). Variable remaining factors and the recent results, however, indicate that this decline may be non-uniform and even over-estimated. Coordinated and regionally adopted efforts for eradication of IDD from all stakeholders should be pursued. Policy makers should take steps to protect future generations and alert concerned organizations about the importance of careful assessments and estimates of iodine nutritional status.

  19. 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.

  20. Nutrition, evolution and thyroid hormone levels - a link to iodine deficiency disorders?

    PubMed

    Kopp, Wolfgang

    2004-01-01

    An increased iodine requirement as a result of significant changes in human nutrition rather than a decreased environmental iodine supply is suggested to represent the main cause of the iodine deficiency disorders (IDD). The pathomechanism proposed is based on the fact that serum concentrations of thyroid hormones, especially of trijodothyronine (T3), are dependent on the amount of dietary carbohydrate. High-carbohydrate diets are associated with significantly higher serum T3 concentrations, compared with very low-carbohydrate diets. While our Paleolithic ancestors subsisted on a very low carbohydrate/high protein diet, the agricultural revolution about 10,000 years ago brought about a significant increase in dietary carbohydrate. These nutritional changes have increased T3 levels significantly. Higher T3 levels are associated with an enhanced T3 production and an increased iodine requirement. The higher iodine requirement exceeds the availability of iodine from environmental sources in many regions of the world, resulting in the development of IDD.

  1. The effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzymes in selenium and/or iodine deficient rats

    PubMed Central

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

    2016-01-01

    Objective(s): Particularly in developing countries, selenium and/or iodine deficiencies are encountered and use of pesticides in agriculture are not well-controlled. Fenvalerate is a pyrethroid insectide used in agriculture and has applications against a wide range of pests. This study was designed to evaluate the effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzyme activities in the presence of iodine and/or selenium deficiency on a rat model. Materials and Methods: Iodine and/or selenium deficiency was induced by feeding three-week-old Wistar rats with a diet containing <0.005 mg selenium kg-1, and/or administering 1% sodium perchlorate in drinking water for 7 weeks. Test groups received fenvalerate (100 mg kg-1 BW IP) for the last 7 days. Hepatic and cerebral microsomal aniline hydroxylase (CYP2E1) and cytosolic glutathione S-transferase (GST) activities were determined. Besides, hepatic NADPH-cytochrome P450 reductase (P450R), ethoxyresorufin O-deethylase (EROD, CYP1A1/1A2) and penthoxyresorufin O-depenthylase (PROD, CYP2B1/2B2), activities were also measured. Results: Fenvalerate had a general inductive effect on the hepatic and cerebral xenobiotic metabolizing enzyme activities. Moreover, enzyme activities were also altered by iodine and/or selenium deficiency, but the effects seemed to be enzyme- and tissue-specific. Conclusion: The inductive effect of fenvalerate, particularly in high dose exposures, may change the metabolism of several xenobiotics, including drugs, as well as endogenous substrates. The effects may vary depending on the selenium and/or iodine status of individual. PMID:27872699

  2. An Increase in Consuming Adequately Iodized Salt May Not Be Enough to Rectify Iodine Deficiency in Pregnancy in an Iodine-Sufficient Area of China

    PubMed Central

    Wang, Zhifang; Zhu, Wenming; Mo, Zhe; Wang, Yuanyang; Mao, Guangming; Wang, Xiaofeng; Lou, Xiaoming

    2017-01-01

    Universal salt iodization (USI) has been implemented for two decades in China. It is crucial to periodically monitor iodine status in the most vulnerable population, such as pregnant women. A cross-sectional study was carried out in an evidence-proved iodine-sufficient province to evaluate iodine intake in pregnancy. According to the WHO/UNICEF/ICCIDD recommendation criteria of adequate iodine intake in pregnancy (150–249 µg/L), the median urinary iodine concentration (UIC) of the total 8159 recruited pregnant women was 147.5 µg/L, which indicated pregnant women had iodine deficiency at the province level. Overall, 51.0% of the total study participants had iodine deficiency with a UIC < 150 µg/L and only 32.9% of them had adequate iodine. Participants living in coastal areas had iodine deficiency with a median UIC of 130.1 µg/L, while those in inland areas had marginally adequate iodine intake with a median UIC of 158.1 µg/L (p < 0.001). Among the total study participants, 450 pregnant women consuming non-iodized salt had mild-moderate iodine deficiency with a median UIC of 99.6 µg/L; 7363 pregnant women consuming adequately iodized salt had a lightly statistically higher median UIC of 151.9 µg/L, compared with the recommended adequate level by the WHO/UNICEF/ICCIDD (p < 0.001). Consuming adequately iodized salt seemed to lightly increase the median UIC level, but it may not be enough to correct iodine nutrition status to an optimum level as recommended by the WHO/UNICEF/ICCIDD. We therefore suggest that, besides strengthening USI policy, additional interventive measure may be needed to improve iodine intake in pregnancy. PMID:28230748

  3. Seven deadly sins in confronting endemic iodine deficiency, and how to avoid them.

    PubMed

    Dunn, J T

    1996-04-01

    Iodine deficiency is a problem for almost all countries of the world. Goiter is its most obvious consequence, but others do more damage, particularly effects on the developing brain. In 1990, most countries and international agencies pledged the virtual elimination of iodine deficiency by the year 2000. The technology for the assessment and implementation is sufficient to attain this goal, but translating its potential into success requires careful planning. This article reviews seven major errors that frequently occur in iodine supplementation programs and offers suggestions for their avoidance. They are 1) unreliable assessment of iodine deficiency: the best indicators are urinary iodine concentration, thyroid size (preferably by ultrasound), blood spot thyroglobulin levels, and neonatal TSH determinations; the best group for surveys is schoolchildren; 2) poor iodine supplementation plan: iodized salt is the preferred supplement; its effective application frequently requires extensive changes in salt production and marketing, and poor handling of these changes will endanger the iodization program; other measures include iodized oil, iodized water, and iodine drops; all are occasionally useful, but the long range solution should generally be iodized salt; 3) exclusion of relevant stake-holders: the program should include not only health authorities but other arms of the government as well (education, commerce, agriculture, and standards), the salt industry, health professionals, and the iodine-deficient community itself; 4) inadequate education: an understanding of the effects of iodine deficiency and the means for its correction is essential at all levels, from government to affected population; 5) insufficient monitoring: the best instruments are urinary iodine levels, iodized salt use, and thyroid size, measured in representative groups at regular intervals with public reporting of results; 6) inattention to cost: the expense of iodization must be recognized

  4. [Solution of Iodine deficiency in the Czech Republic - history and current situation20 years of work of prof. Václav Zamrazil for Commission for the solution of Iodine deficiency].

    PubMed

    Ryšavá, Lydie; Kříž, Jaroslav

    2016-01-01

    Diseases caused by Iodine deficit are preventable. Inter resort Commission for the solution of Iodine deficiency (MKJD) at State Institute for Health (SZU) in Prague has been taking effective measures which satisfied requirements of the Principles for sustainable elimination of diseases caused by Iodine deficiency ICCD WHO: 96 % of households is using iodized salt, average Iodine content is 25 mg/1 kg of salt. Data from studies show ioduria less 100 mcg/l in only 9 per cent of seniors, 5 % of children 7-10 years, 3 % of children 10-12 years. Under 50 mcg only 1 % of children 10-12 years. Median of iodurias is below 300 mcg/l (seniors 185 mcg/l, children 7-10 years 277 mcg/l, children 10-12 years 252 mcg/l). We satisfy 8 of 10 indicators of Principles for Sustainable elimination of diseases caused by Iodine deficiency. Results of screening for congenital hypothyroidism are in keeping with sufficient iodine intake in newborns. Unsatisfactory situation however persist in expectant and breast feeding mothers 16 % [11] 6 % [10] of women included in the respective studies had ioduria below 50 mpg/l. Milk and dairy produce became a rich dietary source of Iodine as cattle feeds are fortified with Iodine. No part of observed human population is exposed Iodine doses higher than 17 mcg/kg. Next target for prevention will be achieving optimal iodine concentration in milk and improvement of iodine saturation of expectant and nursing mothers. Integral part is the monitoring of iodine saturation of population.Key words: dietary exposition - dietary sources of iodine - Inter resort commission for elimination of iodine deficit - iodine deficiency - iodine supply - iodized salt - ioduria.

  5. 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.

  6. 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.

  7. Laser Induced Fluorescence of the Iodine Ion

    DTIC Science & Technology

    2014-09-01

    Fluorescence of the Iodine Ion 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER William A. Hargus, Jr. 5e. TASK NUMBER...SUPPLEMENTARY NOTES Briefing Charts presented at Gaseous Electronics Conference; Raleigh, NC; 5 November 2014. PA#14517 14. ABSTRACT Iodine (I2) has been...discussed seriously as a propellant for Hall effect and other electrostatic thrusters as early as 2000. Atomic iodine has a mass of 126.9 amu, but as

  8. Iodine in Rivers: Indicator of Geologic Effect on Iodine Deficiency Disorders?

    NASA Astrophysics Data System (ADS)

    Huh, Y.; Stewart, A.

    2003-12-01

    A contrast in goiter prevalence between populations living north and south of the Main Karakoram Thrust (MKT) in northeastern Pakistan suggests that plate tectonics may be involved. We report ICP-MS measurements of the total dissolved iodine levels in the headwater tributaries of the Indus River draining either side of the MKT. For global geochemical context, we also analyzed samples from the Lena, Yana, Kolyma, Indigirka, and Anadyr in eastern Siberia, the Orinoco in tropical South America, and rivers in western China and Tibet. We find statistically significant difference in iodine concentration between the right bank tributaries of the Indus draining the Karakoram metamorphic complex north of the MKT and the left bank tributaries draining the Kohistan-Ladakh island arc south of the MKT. At least in these rivers, lithology and the tectonic exposure appear to be more important than atmospheric transport and deposition.

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

    PubMed

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

    2014-01-01

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

  10. 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

  11. Beware of parotitis induced by iodine-containing contrast media.

    PubMed

    Kohat, A K; Jayantee, K; Phadke, R V; Muthu, R; Singh, V; Misra, U K

    2014-01-01

    Carotid stenting is being increasingly used for revascularization of the moderate to severe carotid stenosis and thus its complications are increasingly being recognized. We report a rare complication of induced by iodine contrast in a patient undergoing carotid stenting. s. A 51 year old man after the second stenting developed multiple small infarcts in spite of the distal device. He also had painful parotid swelling which improved within a week. One should be aware of iodine parotitis s in the patients undergoing iodinated contrast study.

  12. Iron and iodine deficiencies among under-2 children, adolescent girls, and pregnant women of Bangladesh: association with common diseases.

    PubMed

    Harun-Or-Rashid, M; Khatun, Uh Farida; Yoshida, Yoshitoku; Morita, Satoshi; Chowdhury, Nuruddin; Sakamoto, Junichi

    2009-02-01

    We examined the frequency of iron and iodine deficiencies and associations of iron and iodine deficiencies with common diseases among under-2 children, adolescent girls, and pregnant women of Bangladesh. We assayed the blood hemoglobin concentration in 395 under-2 children, 355 adolescent girls, and 263 pregnant women, the urinary iodine concentration of those adolescent girls and pregnant women, and the iodine level of all household salt specimens. The history of common diseases within their previous 2 weeks were also obtained from recall to explore the associations of iron and iodine deficiencies with common diseases. Anemia was found in 49.1% of children, 24.8% of adolescent girls, and 44.4% of pregnant women using defined cut-off values (Hb < 11.0 g/dL for under-2 children and pregnant women; <12.0 g/dL for adolescent girls). Prevalence of iodine deficiencies (urinary iodine <100 microg/L) was 38.4% in adolescent girls and 39.4% in pregnant women, and 39.4% of salt specimens had inadequate iodine (<15 ppm). The relative risk (RR) and 95% confidence intervals (CI) were estimated and adjusted for age, sex, and gestational age to explore the associations of iron and iodine deficiencies with common diseases. The RR of anemia was increased for fever (RR = 1.7, 95% CI = 1.3-2.3), ear infection (RR = 3.4, 95% CI = 1.3-8.5), skin disease (RR = 1.4, 95% CI = 0.9-2.2), and pneumonia (RR = 3.7, 95% CI = 0.7-19.5). The RR of iodine deficiency was elevated for diarrhea/dysentery (RR = 2.2, 95% CI = 1.1l-4.4) and eye infection (RR = 2.1, 95% CI = 0.5-9.4). We concluded that iron and iodine deficiencies are quite high among the Bangladeshi population. Observed associations of iron and iodine deficiencies with common diseases indicated the necessity of eliminating iron and iodine deficiencies from this vulnerable population through strengthening of iron and iodine supplementation, in order to prevent diseases and promote health conditions.

  13. Iodine

    MedlinePlus

    ... applying povidone-iodine reduces the risk of blood stream infections for people with hemodialysis catheters. However, most ... in which chyle is present in the urine stream. This causes the urine to appear milky white. ...

  14. Increase in iodine deficiency disorder due to inadequate sustainability of supply of iodized salt in District Solan, Himachal Pradesh.

    PubMed

    Kapil, Umesh; Pandey, R M; Jain, Vandana; Kabra, Madhulika; Sareen, Neha; Bhadoria, Ajeet Singh; Vijay, Jyoti; Nigam, Sukirty; Khenduja, Preetika

    2013-12-01

    Himachal Pradesh is a known endemic area for iodine deficiency disorders. A study was conducted in district Solan with the objective of assessing the prevalence of iodine deficiency disorders in school-age children. Thirty clusters were selected by using the probability-proportionate-to-size cluster sampling methodology. Clinical examination of the thyroid of 1898 children in the age-group of 6-12 years was conducted. Urine and salt samples were collected. The total goiter rate was found to be 15.4%. Median urinary iodine excretion level was 62.5 μg/l. Only 39% of the salt samples had iodine content of ≥15 ppm. Mild iodine deficiency was present in the subjects studied.

  15. 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...

  16. Incidence of thyroid cancer in the selected areas of iodine deficiency in Poland.

    PubMed

    Szybiński, Z; Huszno, B; Zemla, B; Bandurska-Stankiewicz, E; Przybylik-Mazurek, E; Nowak, W; Cichon, S; Buziak-Bereza, M; Trofimiuk, M; Szybiński, P

    2003-01-01

    The aim of the study was to evaluate the incidence rate (IR), trend and histotype of the differentiated thyroid cancer in the selected areas with varying iodine deficiency. The study was carried out in three areas: Krakow, (Carpathian endemic goiter area with 1.99 million mixed rural and urban population), Gliwice (Upper Silesia--moderate iodine deficiency area mostly industrial with 4.89 million inhabitants) and Olsztyn (slight iodine deficiency area, mainly rural with 0.77 million inhabitants). Between 1990 and 2001, in the study area 2691 newly diagnosed cases of malignant neoplasms of the thyroid gland were registered. In over 80% of patients it was differentiated thyroid cancer: mainly in women over 40 years, with F/M ratio 5.8. The highest percentage of papillary cancer 72.9% was observed in Olsztyn and lowest--50.0%--in Krakow and Nowy Sacz districts. In this period of time incidence rate of differentiated thyroid cancer in women increased in Kraków, Gliwice, and Olsztyn from 1.51 to 9.34 in 1998 1.27 to 5.74 in 1999 and from 2.52 to 11.35 in 2001 respectively. In the youngest (0-20 years) age group no significant increase of IR was observed. Between 1998 and 2001 the dynamics of increase of the thyroid cancer incidence markedly diminished. In conclusion it was hypothesised that an increase in IR of differentiated thyroid cancer in the study area was caused mainly by the suspension of iodine prophylaxis in 1980 and was diminished by the introduction of an obligatory model of iodine prophylaxis in 1996/1997. It was modified in terms of histotype and dynamics of increase by exposure to ionizing radiation. A very specific group at risk on the population level were women aged 20-40 years in the reproductive age exposed to iodine deficiency after suspension of iodine prophylaxis in 1980 and to radiation after the Chernobyl accident in 1986.

  17. [Long-term effect of iodine deficiency on growth and food utilization rate in second filial generation rats].

    PubMed

    Muyeseer, Ainiwaer; Zhang, G X; Wang, J; Liu, Y; Meng, X H; Liu, Q

    2017-02-06

    were (465.0±27.7), (658.4±28.6) and (423.0±13.2), (548.0±18.8) g, respectively, which were significantly lower than that of the NI group ((499.5±21.8), (760.8±33.0) g) (P<0.001). Moreover, the food utilization rate of female rats in the LI and LII groups was (8.7±0.4)% and (6.0±0.58)%, which was lower than that of the NI group ((11.7±3.5)%) (P<0.001); similarly, male rats showed rates of (8.9±1.5)% and (6.9±1.31)%, respectively, which were lower than that of the NI group ((13.7±3.0)%) (P<0.001). After 270 days, the level of T3 in the LI and LII groups were (0.45±0.10) and (0.34±0.15) ng/ml, respectively, which was significantly lower than that of the NI group ((0.91±0.49) ng/ml) (P<0.01). Moreover, the level of T4 were (69.02±27.87) , (53.18±13.53) ng/ml in LI and LII groups, respectively, which was lower than that of the NI group ((76.69±29.42) ng/ml) (P<0.05). Conclusion: This study indicated that iodine deficiency induced by a long-term low-iodine diet can cause changes in weight, food intake, and food utilization rate among second filial iodine deficiency rats. More importantly, the iodine content in low-iodine food impacts these parameters.

  18. [A project of the Ministry of Health for iodine prophylaxis in Italy: Salt in food for the prophylaxis of iodine deficiency and the prevention of hypertension].

    PubMed

    Marabelli, R; Guidarelli, L; Copparoni, R

    1998-01-01

    A main goal to achieve in order to reduce the incidence of wrong nutritional habit associated diseases, according to the engagement taken on the FAO/WHO International Conference on Nutrition 1992 is the eradication of the endemic goitre and other iodine deficiency disorders. Iodine nutritional lack is, in Italy, a heavy public health problem; above 10% of population (about 5 million) has to bear thyroid troubles and in many of the Italian regions such a kind of pathology may involve more than 20% of scholastic population. All these disorders could be completely eradicated by means of a continuous and generalized iodine prophylaxis, as it has already been verified in several European countries. The most effective way to ensure the correct daily intake of iodine is the substitution of the usual cooking salt by iodine enriched salt; salt is in fact eaten by everybody at daily rates ungoverned by economical factors as it is a low cost product. Due to the heavy social relevance of this problem, an educational campaign is going on, from the Italian Ministry of Health "Salt in food for iodine deficiency disorder prophylaxis and hypertension prevention". The purpose is to achieve, by means of a unique message based on salt, a double goal in terms of public health: eradicating endemic goitre and preventing hypertension (reducing the salt global intake to less than 6 g/day).

  19. Iodine deficiency and brain development in the first half of pregnancy.

    PubMed

    de Escobar, Gabriella Morreale; Obregón, María Jesús; del Rey, Francisco Escobar

    2007-12-01

    An inadequate supply of iodine during gestation results in damage to the foetal brain that is irreversible by mid-gestation unless timely interventions can correct the accompanying maternal hypothyroxinemia. Even mild to moderate maternal hypothyroxinemia may result in suboptimal neurodevelopment. This review mainly focuses on iodine and thyroid hormone economy up to mid-gestation, a period during which the mother is the only source for the developing brain of the foetus. The cerebral cortex of the foetus depends on maternal thyroxine (T4) for the production of the 3',3,5-tri-iodothyronine (T3) for nuclear receptor-binding and biological effectiveness. Maternal hypothyroxinemia early in pregnancy is potentially damaging for foetal brain development. Direct evidence has been obtained from experiments on animals: even a relatively mild and transient hypothyroxinemia during corticogenesis, which takes place mostly before mid-gestation in humans, affects the migration of radial neurons, which settle permanently in heterotopic locations within the cortex and hippocampus. Behavioural defects have also been detected. The conceptus imposes important early changes on maternal thyroid hormone economy that practically doubles the amount of T4 secreted something that requires a concordant increase in the availability of iodine, from 150 to 250-300 microg I day- 1. Women who are unable to increase their production of T4 early in pregnancy constitute a population at risk for having children with neurological disabilities. As a mild to moderate iodine deficiency is still the most widespread cause of maternal hypothyroxinemia, the birth of many children with learning disabilities may be prevented by advising women to take iodine supplements as soon as pregnancy starts, or earlier if possible, in order to ensure that their requirements for iodine are met.

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

    PubMed

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

    2016-06-01

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

  1. Neonatal thyrotropin profile as an index for severity of iodine deficiency and surveillance of iodine prophylactic program.

    PubMed

    Rajatanavin, R; Unachak, K; Winichakoon, P; Chailurkit, L O; Vilasdechanon, N; Tananchai, P; Srinawat, S

    1997-08-01

    Neonatal serum thyrotropin (TSH) level has been proposed as an index for the monitoring and surveillance of an iodine prophylactic program. We have determined an effective way to put this idea into practice. During the first phase of our study, neonatal serum TSH levels were obtained from umbilical cord blood of neonates born in Chiangmai and Nan provinces, where several districts were areas of severe iodine deficiency, and were compared with those of neonates born in Bangkok, which was a control area. The median and (95% CI [confidence interval]) of serum TSH level of neonates born in Chiangmai 5.8 (5.7-5.9) microU/mL was significantly higher than in Nan 5.1 (5.0-5.2) microU/mL, and in Bangkok 3.7 (3.7-3.8) microU/mL. Neonatal serum free thyroxine (FT4) concentration in Bangkok was higher than in Nan; while the reciprocal was true for neonatal TSH concentration in randomly selected samples (FT4 1.6 [1.6-1.7] ng/dL vs. 1.5 [1.5-1.6] ng/dL and TSH 3.5 [3.3-3.9] microU/mL vs. 5.5 [5.2-5.9] microU/mL, respectively.) When odds ratio of the likelihood of having neonatal TSH level higher than in Bangkok was calculated using 95th percentile value of neonatal TSH level in Bangkok as a cut-off point, the odds ratio of TSH profile in all districts in Chiangmai and Nan were greater than unity. In the second phase of our study, data were collected from 32 district and 10 provincial hospitals. The optimum number of samples in each hospital derived from the first phase of our study was at least 178. Discrepancy between goiter rate and odds ratio of TSH profile was observed, but there was a significant correlation between the two indices (r = 0.67, p < .001). Our study confirmed the practical utility of neonatal TSH profile as a biological index for assessment and monitoring and surveillance of an iodine prophylactic program at a district hospital in a developing country.

  2. 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

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

    PubMed

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

    2016-08-18

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

  4. 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...

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

    PubMed

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

    2009-12-01

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

  6. 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.

  7. 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.

  8. Maternal marginal iodine deficiency limits dendritic growth of cerebellar purkinje cells in rat offspring by NF-κB signaling and MAP1B.

    PubMed

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

    2017-04-01

    Iodine deficiency (ID) during early pregnancy had an adverse effect on children's psychomotor and motor function. It is worth noting that maternal marginal ID tends to be a common public health problem. Whether marginal ID potentially had adverse effects on the development of cerebellum and the underlying mechanisms remain unclear. Therefore, our aim was to study the effects of marginal ID on the dendritic growth in filial cerebellar Purkinje cells (PCs) and the underlying mechanism. In the present study, we established Wistar rat models by feeding dam rats with a diet deficient in iodine and deionized water supplemented with potassium iodide. We examined the total dendritic length using immunofluorescence, and Western blot analysis was conducted to investigate the activity of nuclear factor-κB (NF-κB) signaling and microtubule-associated protein 1B (MAP1B). Our results showed that marginal ID reduced the total dendritic length of cerebellar PCs, slightly down-regulated the activity of NF-κB signaling and decreased MAP1B in cerebellar PCs on postnatal day (PN) 7, PN14, and PN21. Our study may support the hypothesis that decreased T4 induced by marginal ID limits PCs dendritic growth, which may involve in the disturbance of NF-κB signaling and MAP1B on the cerebellum. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1241-1251, 2017.

  9. [Iodine deficiency in the Cirque of Salazie (Reunion Island). Analysis of nutritional causes and study of their consequences].

    PubMed

    Jaffiol, C; Manderscheid, J C; Rouard, L; Dhondt, J L; Arguillère, S; Bourdoux, P

    1997-12-01

    Randomized subjects (n = 294), (35 young children, 6-30 months old--91 children 8.6 +/- 0.7 years, 116 teenagers 13.2 +/- 1.9 y--52 young women 28.5 +/- 6.1 y) leaving in a mountainous area of Reunion Island (Cirque de Salazie) were evaluated according to the following: a questionnaire related to food intake, cervical palpation for thyroid size evaluation and collections of urine and foods (natural and mineral water, breast and commercial milk and salt) for iodine measurement. Neonatal TSH of 308 new borns in Salazie were compared to TSH of 300 new-borns of Lille (France). The prevalence of goiter increases with age (0% in young children, 12.1% in children, 23.3% in teenagers, 38.4% in women) whereas median urinary iodine (microgram/dl) decreases in the same groups (12-7.8-5.6-4.2). The intake of milk and dairy products significantly decreases from children to adults. Neonatal TSH values are significantly higher in Salazie than in Lille (p < 0.005). Natural and mineral water, breast milk and salt contain little iodine. In conclusion iodine deficiency is present in this area of Reunion Island with a significant increment of neonatal TSH values.

  10. 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

  11. Combating iodine and iron deficiencies through the double fortification of fish sauce, mixed fish sauce, and salt brine.

    PubMed

    Chavasit, Visith; Nopburabutr, Preeyacha; Kongkachuichai, Ratchanee

    2003-06-01

    Two iodine and seven iron compounds were tested for use in the fortification of pure fish sauce, mixed fish sauce, and salt brine for cooking as a means to combat iodine and iron deficiencies. Ferrous sulfate, sodium iron ethylenediaminetetraacetic acid, ferric ammonium citrate, and ferrous lactate were combined with potassium iodide with no effect on sensory quality. Product shelf-life testing revealed that no iron or iodine losses occurred during a three-month storage period. Although the color of most products darkened, the color was not significantly different from that of nonfortified products after two to three months. Sensory home-use tests revealed that the fortified products were acceptable to highly acceptable, with only 1.2% to 8.2% of the dishes cooked using the fortified products being reported as discolored. The cost of fortification was minimal, at 0.13 to 2.73 baht per bottle (750 ml) (42 baht = US$1). Consequently, these products show a potential for inclusion in national programs for the prevention of micronutrient deficiencies in Asian countries where fish sauce and its products are routinely consumed.

  12. 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

  13. Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter

    PubMed Central

    Mao, Xia; Yan, Chen; Guo, Xiaodong; Guo, Qiuyan; Liu, Zhenli; Song, Zhiqian; Lin, Na

    2016-01-01

    Haizao Yuhu Decoction (HYD), a famous multi-component herbal formula, has been widely used to treat various thyroid-related diseases, including iodine-deficient goiter. Herb pair Thallus Sargassi Pallidi (HZ) and Radix Glycyrrhizae (GC), one of the so-called “eighteen antagonistic medicaments”, contains in HYD. To explore pharmacological mechanisms of HYD acting on iodine-deficient goiter and to provide evidence for potential roles of herb pair HZ and GC in HYD, our genome-wide microarray detection and network analysis identified a list of goiter-related genes, mainly involved into the alterations in hypothalamus-pituitary-thyroid/gonad/growth axes. Then, the disease genes-drug genes interaction network illustrated the links between HYD regulating genes and goiter-related genes, and identified the candidate targets of HYD acting on goiter. Functionally, these candidate targets were closely correlated with thyroid hormone synthesis. Moreover, the potential regulating genes of herb pair HZ and GC were revealed to be crucial components in the pathway of thyroid hormone synthesis. The prediction results were all verified by following experiments based on goiter rats. Collectively, this integrative study combining microarray gene expression profiling, network analysis and experimental validations offers the convincing evidence that HYD may alleviate iodine-deficient goiter via regulating thyroid hormone synthesis, and explains the necessity of herb pair HZ and GC in HYD. Our work provides a novel and powerful means to clarify the mechanisms of action for multi-component drugs such as herbal formulae in a holistic way, which may improve drug development and applications. PMID:27384475

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

    PubMed

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

    1981-10-01

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

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

    PubMed

    Voronych-Semchenko, N M

    2007-01-01

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

  16. UVRAG Deficiency Exacerbates Doxorubicin-Induced Cardiotoxicity.

    PubMed

    An, Lin; Hu, Xiao-Wen; Zhang, Shasha; Hu, Xiaowen; Song, Zongpei; Naz, Amber; Zi, Zhenguo; Wu, Jian; Li, Can; Zou, Yunzeng; He, Lin; Zhu, Hongxin

    2017-02-22

    Doxorubicin (DOX) is an effective chemotherapeutic drug in the treatment of various types of cancers. However, its clinical application has been largely limited by potential development of cardiotoxicity. Previously we have shown that ultra-violet radiation resistance-associated gene (UVRAG), an autophagy-related protein, is essential for the maintenance of autophagic flux in the heart under physiological conditions. Here, we sought to determine the role of UVRAG-mediated autophagy in DOX-induced cardiotoxicity. Mouse models of acute or chronic DOX-induced cardiotoxicity were established. UVRAG deficiency exacerbated DOX-induced mortality and cardiotoxicity manifested by increased cytoplasmic vacuolization, enhanced collagen accumulation, elevated serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, higher ROS levels, aggravated apoptosis and more depressed cardiac function. Autophagic flux was impaired in DOX-induced cardiotoxicity. UVRAG deficiency aggravated impaired autophagic flux in DOX-induced cardiotoxicity. Intermittent fasting restored autophagy and ameliorated pathological alterations of DOX-induced cardiotoxicity. Collectively, our data suggest that UVRAG deficiency exacerbates DOX-induced cardiotoxicity, at least in part, through aggravation of DOX-induced impaired autophagic flux. Intermittent fasting, which restores blunted autophagic flux and ameliorates pathology in the mouse models of DOX-induced cardiotoxicity, may be used as a potential preventive or therapeutic approach for DOX cardiotoxicity.

  17. UVRAG Deficiency Exacerbates Doxorubicin-Induced Cardiotoxicity

    PubMed Central

    An, Lin; Hu, Xiao-wen; Zhang, Shasha; Hu, Xiaowen; Song, Zongpei; Naz, Amber; Zi, Zhenguo; Wu, Jian; Li, Can; Zou, Yunzeng; He, Lin; Zhu, Hongxin

    2017-01-01

    Doxorubicin (DOX) is an effective chemotherapeutic drug in the treatment of various types of cancers. However, its clinical application has been largely limited by potential development of cardiotoxicity. Previously we have shown that ultra-violet radiation resistance-associated gene (UVRAG), an autophagy-related protein, is essential for the maintenance of autophagic flux in the heart under physiological conditions. Here, we sought to determine the role of UVRAG-mediated autophagy in DOX-induced cardiotoxicity. Mouse models of acute or chronic DOX-induced cardiotoxicity were established. UVRAG deficiency exacerbated DOX-induced mortality and cardiotoxicity manifested by increased cytoplasmic vacuolization, enhanced collagen accumulation, elevated serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, higher ROS levels, aggravated apoptosis and more depressed cardiac function. Autophagic flux was impaired in DOX-induced cardiotoxicity. UVRAG deficiency aggravated impaired autophagic flux in DOX-induced cardiotoxicity. Intermittent fasting restored autophagy and ameliorated pathological alterations of DOX-induced cardiotoxicity. Collectively, our data suggest that UVRAG deficiency exacerbates DOX-induced cardiotoxicity, at least in part, through aggravation of DOX-induced impaired autophagic flux. Intermittent fasting, which restores blunted autophagic flux and ameliorates pathology in the mouse models of DOX-induced cardiotoxicity, may be used as a potential preventive or therapeutic approach for DOX cardiotoxicity. PMID:28225086

  18. 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.

  19. 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...

  20. 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 ...

  1. Moderate-to-Severe Iodine Deficiency in the "First 1000 Days" Causes More Thyroid Hypofunction in Infants Than in Pregnant or Lactating Women.

    PubMed

    Stinca, Sara; Andersson, Maria; Herter-Aeberli, Isabelle; Chabaa, Laila; Cherkaoui, Mohamed; El Ansari, Nawal; Aboussad, Abdelmounaim; Weibel, Sandra; Zimmermann, Michael B

    2017-04-01

    Background: Iodine deficiency early in the life cycle-the "first 1000 days"-can cause hypothyroidism and irreversibly impair neuromotor development. However, the relative vulnerability among women and infants during this critical period is unclear, making it difficult for country-based programs with limited resources to prioritize their iodine interventions.Objective: Our aim was to determine the prevalence of thyroid hypofunction in women and infants living in an area of moderate-to-severe iodine deficiency.Methods: In a cross-sectional survey in Morocco, we measured urinary iodine concentrations (UICs) and concentrations of thyroid-stimulating hormone (TSH) and total or free thyroxine (TT4 or fT4, respectively) in women of reproductive age (n = 156), pregnant women (n = 245), and lactating women (n = 239) and their young infants (n = 239). We calculated daily iodine intakes and measured iodine concentrations in breast milk and household salt. We compared the incidence of hypothyroidism between the 3 groups of women and with the infants.Results: Women of reproductive age, pregnant women, and lactating women had median (IQR) UICs of 41 (29-63), 32 (17-58), and 35 (19-62) μg/L; and estimated iodine intakes were ∼60%, 22%, and 26% of Recommended Nutrient Intakes (RNIs). The infants' median UIC was 73 (28-157) μg/L, which was greater than for all 3 groups of women (P < 0.001), and their dietary intakes were 27% of the RNI. The prevalence of hypothyroidism was not significantly different between the 4 groups, whereas the prevalence of hypothyroxinemia was higher in infants (40%) than in the 3 groups of women (11-14%) (P < 0.001). The median breast-milk iodine concentration was 42 (26-81) μg/L. Only 6% of salt samples were adequately iodized to a concentration of ≥15 ppm; 54% were inadequately iodized and 40% contained no measurable iodine.Conclusions: In an area of moderate-to-severe iodine deficiency, the prevalence of thyroid hypofunction is ∼4-fold higher

  2. Radioactive Iodine

    MedlinePlus

    ... Phone Home » Radioactive Iodine Leer en Español Radioactive Iodine Iodine is essential for proper function of the ... that takes up and holds onto iodine. Radioactive Iodine FAQs WHAT IS RADIOACTIVE IODINE (RAI)? Iodine, in ...

  3. Iodine revisited.

    PubMed

    Cooper, Rose A

    2007-06-01

    Iodine is an antiseptic that has been used in wound care for more than 150 years. Traditional formulations of iodine had serious limitations that were reduced in later products. Much has been written about iodine and opinions on its clinical efficacy are divided. There have been reviews of the chemical properties of iodine, its antimicrobial activity, human physiology, cytotoxicity and its clinical effectiveness, but few have addressed all these aspects. With the recent development of iodine-containing wound care products and the continued publication of laboratory and clinical studies, it seems timely to reassess the evidence relating to the effectiveness of iodine for treating wounds. This literature review attempts to provide an appropriate chemical and physiological background of the characteristics of iodine in order to provide a sound basis for understanding the available microbiological and clinical data. It will show that understanding the factors that contribute to the activity and potential cytotoxicity of iodine are important in evaluating the clinical evidence. Although definitive studies are needed, the sustained delivery of low doses of free iodine offers the potential to inhibit a broad range of microbial species without selecting for resistant strains or inducing cytotoxic effects.

  4. Searching for the most effective thyrotropin (TSH) threshold to rule-out autonomously functioning thyroid nodules in iodine deficient regions.

    PubMed

    Giovanella, Luca; D'Aurizio, Federica; Campenni', Alfredo; Ruggeri, Rosaria Maddalena; Baldari, Sergio; Verburg, Frederik Anton; Trimboli, Pierpaolo; Ceriani, Luca

    2016-12-01

    The purpose of this study is to evaluate the distribution of thyrotropin (TSH) values in patients with autonomously functioning thyroid nodules and to set a TSH threshold above which thyroid scintigraphy would be obviated. Four hundred fifty one patients were included in the present study. Inclusion criteria were age > 18 years, TSH levels between 0.40 and 4.0 mIU/L, detection of a single solid or predominantly solid thyroid nodule >10 mm in the longest diameter. Thyroid ultrasound and thyroid scintigraphy with (99m)Tc-pertechnetate were performed concurrently in all patients. Among 451 enrolled patients, 173 (38 %) had an autonomously functioning thyroid nodules, of which 137 (79 %) with a normal TSH level. Demographic data and nodules' volume were not significantly different in patients with autonomously functioning thyroid nodules and non-functioning nodules, respectively. However, TSH levels were nonetheless significantly lower in patients with autonomously functioning thyroid nodules compared to those with non-functioning nodules (p < 0.001). Adopting a TSH cutoff level at 2.38 mUI/L, all autonomously functioning thyroid nodules were correctly identified (i.e., 100 % sensitivity) with a 100 % negative predictive value. Our study showed a very high prevalence of autonomously functioning thyroid nodules in mildly iodine-deficient regions and confirmed that serum TSH is not an effective screening test to diagnose an autonomously functioning thyroid nodules. Our data add arguments in favor of the first-line use of thyroid scintigraphy to assess thyroid nodules, at least in iodine deficient areas. As all scintigraphically detected autonomously functioning thyroid nodules had a TSH level below 2.38 mUI/L, a thyroid scintigraphy should be omitted when higher TSH values are found in patients carrying a thyroid nodule.

  5. 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.

  6. 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.

  7. 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

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

    PubMed

    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. 99mTc-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 99mTc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients. 2) The organification defect induced by iodine excess is greater in iodide-induced

  9. Toward an ecosocial epidemiological approach to goiter and other iodine deficiency disorders: a case study of India's technocratic program for universal iodization of salt.

    PubMed

    Priya, Ritu; Kotwal, Atul; Qadeer, Imrana

    2009-01-01

    The program of universal salt iodization (USI) was intensified in the 1990s. Unfortunately, a recent World Health Organization review finds that there was a global increase of 31.7 percent in total goiter rate from 1993 to 2003. However, the WHO review places only 1 country as severely, 13 as moderately, and 40 as mildly deficient in populations' iodine nutrition, and places 43 countries at optimal, 24 at high, and 5 at excessive levels of iodine nutrition. Thus, it is imperative to weigh the benefits and risks of intensifying USI further. The WHO review places India in the category of "adequate" iodine nutrition, but in 2005 the Government of India promulgated a universal ban on sale of non-iodized salt, calling iodine deficiency disorders (IDDs) a major public health problem. This article attempts to understand these contradictions and weigh the benefits and costs of USI. Based on a review of studies since the 1920s, the authors reconstruct the evolution of IDD control in India. Conceptual and methodological limitations challenge the evidence base and rationale of stricter implementation of USI now. Finding evidence for its negative impact, the authors recommend a reexamination of the USI strategy and propose a safer, people-centered, ecosocial epidemiological approach rather than a universal legal ban.

  10. Iodine-induced hyperthyroidism as combination of different etiologies: an overlooked entity in the elderly.

    PubMed

    Foppiani, Luca; Cascio, Christian; Lo Pinto, Giuliano

    2016-10-01

    Iodine-induced thyrotoxicosis, which raises several diagnostic and therapeutical challenges, is often overlooked. Hyperthyroidism can induce atrial fibrillation, a harmful arrhythmia which can precipitate heart failure and cause stroke. We report the case of an elderly man who was diagnosed with tachyfibrillation secondary to hyperthyroidism. Thyroid hyperfunction was subsequently related both to previous amiodarone therapy (probably mixed form) and the recent use of iodinated contrast medium for computed tomography scan. Thyroid ultrasonography showed a plongeant multinodular goitre. After initial worsening, thyroid function improved slowly but progressively on high-dose thyreostatic therapy combined with steroid therapy; tachyfibrillation caused heart failure and a thrombus in the left atrium, and proved initially resistant to combined antiarrhythmic treatments. Progressive reduction in thyroid hormone levels, together with combined cardiologic therapies, controlled the heart rate, though atrial fibrillation persisted; anticoagulant therapy resolved the atrial thrombus. Alterations in thyroid function are common in amiodarone-treated patients, who therefore require regular hormonal checks. The different forms of amiodarone-induced thyrotoxicosis must be investigated, since they require different therapies, though mixed forms often occur. The superimposition of further iodine excess due to other causes may be catastrophic and cause severe cardiac problems in these patients.

  11. Analysis of the Contribution of Charge Transport in Iodine-125 induced DNA Damage

    PubMed Central

    Ndlebe, Thabisile; Panyutin, Igor; Neumann, Ronald

    2009-01-01

    Auger electron emitters, like iodine-125, are the radionuclides of choice for gene-targeted radiotherapy. The highly localized damage they induced in DNA is produced by three mechanisms: direct damage by the emitted Auger electrons, indirect damage by diffusible free radicals produced by Auger electrons travelling in water, and charge neutralization of the residual, highly positively charged, tellurium daughter atom by stripping electrons from covalent bonds of neighboring residues. The purpose of our work was to determine whether these mechanisms proceed through an intermediate energy transfer step along DNA. It was proposed that this intermediate step proceeds through the charge transport mechanism in DNA. Conventional charge transport has been described as either a hopping mechanism initiated by charge injection into DNA and propagated by charge migration along the DNA, or a tunneling mechanism in which charge moves directly from a donor to an acceptor within DNA. Well-known barriers for the hopping mechanism were used to probe the role of charge transport in 125I induced DNA damage. We studied their effect on the distribution of DNA breaks produced by the decay of iodine-125 in samples frozen at −80°C. We found that these barriers had no measurable effect on the iodine-125 breaks distribution. PMID:20041764

  12. Prevalence of simple nodular goiter and Hashimoto's thyroiditis in current, previous, and never smokers in a geographical area with mild iodine deficiency.

    PubMed

    Rendina, D; De Palma, D; De Filippo, G; De Pascale, F; Muscariello, R; Ippolito, R; Fazio, V; Fiengo, A; Benvenuto, D; Strazzullo, P; Galletti, F

    2015-03-01

    Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

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

    PubMed Central

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

    1997-01-01

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

  14. 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.

  15. Perforin deficiency attenuates collagen-induced arthritis

    PubMed Central

    Bauer, Kristin; Knipper, Annika; Tu-Rapp, Hoang; Koczan, Dirk; Kreutzer, Hans-Jürgen; Nizze, Horst; Mix, Eilhard; Thiesen, Hans-Juergen; Holmdahl, Rikard; Ibrahim, Saleh M

    2005-01-01

    Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8+ T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial hyperplasia. In this study we examined the role of perforin (pfp), a key molecule of the cytotoxic death pathway that is expressed mainly in CD8+ T cells, for the pathogenesis of CIA. We generated DBA/1J mice suffering from mutations of the pfp molecule, DBA/1J-pfp-/-, and studied their susceptibility to arthritis. As a result, pfp-deficient mice showed a reduced incidence (DBA/1J-pfp+/+, 64%; DBA/1J-pfp-/-, 54%), a slightly delayed onset (onset of disease: DBA/1J-pfp+/+, 53 ± 3.6; DBA/1J-pfp-/-, 59 ± 4.9 (mean ± SEM), and milder form of the disease (maximum disease score: DBA/1J-pfp+/+, 7.3 ± 1.1; DBA/1J-pfp-/-, 3.4 ± 1.4 (mean ± SEM); P < 0.05). Concomitantly, peripheral T cell proliferation in response to the specific antigen bovine collagen II was increased in pfp-/- mice compared with pfp+/+ mice, arguing for an impaired killing of autoreactive T cells caused by pfp deficiency. Thus, pfp-mediated cytotoxicity is involved in the initiation of tissue damage in arthritis, but pfp-independent cytotoxic death pathways might also contribute to CIA. PMID:15987490

  16. 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

  17. Consequences of excess iodine

    PubMed Central

    Leung, Angela M.; Braverman, Lewis E.

    2014-01-01

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

  18. Flow Measurements of Translational-Rotational Nonequilibrium Using Laser-Induced Iodine Fluorescence

    NASA Astrophysics Data System (ADS)

    Cecil, Eric; McDaniel, James C.

    2011-05-01

    A shock wave impingement flow was studied under low temperature, low density conditions in a hypersonic free-jet wind tunnel. A sharp-edged flat plate was placed at zero incidence in the hypersonic core of a free-jet of nitrogen gas at Mach 12; a right circular cylinder mounted in the middle of the plate projected out normal to the plate surface. The oblique shock produced at the plate leading edge impinged on the detached bow shock wave produced by the cylinder. The symmetry plane in the flow was studied using a laser sheet-beam probe from a narrow-bandwidth laser source, which induced fluorescence in iodine molecules seeded in the gas. Fluorescence patterns produced by the sheet-beam were recorded by a charge-coupled device camera as the laser frequency was tuned in increments over a range spanning two distinct absorption lines in the iodine spectrum. The fluorescence intensity-versus-laser excitation frequency data recorded at each pixel was least-squares fitted to a nonequilibrium model of the iodine spectrum to estimate local translational and rotational temperature, velocity, and density. Contour plots of these results are presented at a resolution equal to roughly one mean-free-path of the oncoming flow at the plate leading edge. Profile plots of translational and rotational temperature on the plate are presented.

  19. Calcium deficiency cannot induce obesity in rats.

    PubMed

    Paradis, S; Cabanac, M

    2005-06-30

    If intake of a required nutrient--here calcium--affects body weight, the effect must be mediated by a change in the body weight set-point. Thus, the controversial 'anti-obesity' influence of high calcium intake should decrease the body weight set-point. Diets differing in calcium content were assigned to three groups of rats. The effects of the diets on body weight, BMI, fat content, plasma calcium, body weight set-point, food intake, and preference for various calcium solutions were measured after 6 weeks of calcium deprivation or supplementation, and again after a further 6 weeks of recovery on a regular diet. After 6 weeks, the low-calcium diet had induced calcium deficiency but had failed to raise the body weight set-point. Nor had it produced obesity or fat accumulation. After 6 weeks of recovery, body weight and fat content were no higher in calcium-deprived rats than in the control or supplemented rats. In this experiment, low-calcium intake failed to cause obesity and did not raise the body weight set-point. The results indicate that calcium intake probably does not affect body weight.

  20. Copper deficiency potentiates ethanol induced liver damage

    SciTech Connect

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

    1992-02-26

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

  1. Positive association of the DIO2 (deiodinase type 2) gene with mental retardation in the iodine-deficient areas of China

    PubMed Central

    Guo, T; Zhang, F; Yang, M; Gao, X; Bian, L; Duan, S; Zheng, Z; Gao, J; Wang, H; Li, R; Feng, G; St, C; He, L

    2004-01-01

    Background: Iodine deficiency is the commonest cause of preventable mental retardation (MR) worldwide. However, in iodine-deficient areas not everyone is affected and familial aggregation is common. This suggests that genetic factors may also contribute. Thyroid hormone (TH) plays an important role in fetal and early postnatal brain development. The pro-hormone T4 (3,3',5,5'-triiodothyronine) is converted in the brain to its active form, T3, or its inactive metabolite, reverse T3, mainly by the action of deiodinase type 2 (DIO2). Methods: To investigate the potential genetic contribution of the DIO2 gene, we performed a case-control association study using three common SNPs in the gene (rs225014, rs225012, and rs225010) that were in strong linkage disequilibrium with each other. Results: Single marker analysis showed a positive association of MR with rs225012 and rs225010. Particularly with rs225012, TT genotype frequency was significantly higher in MR cases than in controls (χ2 = 9.18, p = 0.00246). When we compared the distributions of common haplotypes, we also found significant differences between mental retardation and controls in the haplotype combination of rs225012 and rs225010 (χ2 = 15.04, df 2, global p = 0.000549). This association remained significant after Bonferroni correction (p = 0.0016470). Conclusion: We conclude that allelic variation in the DIO2 gene may affect the amount of T3 available and in an iodine-deficient environment may partly determine overall risk of MR. PMID:15286152

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

    PubMed

    Fedynchuk, G V; Maliar, V A

    2015-01-01

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

  3. 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.

  4. 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.

  5. TRAIL and DR5 promote thyroid follicular cell apoptosis in iodine excess-induced experimental autoimmune thyroiditis in NOD mice.

    PubMed

    Yu, Xiujie; Li, Lanying; Li, Qingxin; Zang, Xiaoyi; Liu, Zebing

    2011-11-01

    Death receptor-mediated apoptosis has been implicated in target organ destruction in patients with chronic autoimmune thyroiditis. Several apoptosis signaling pathways, such as Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), have been shown to be active in thyroid cells and may be involved in destructive thyroiditis. Thyroid toxicity of iodide excess has been demonstrated in animals fed with an iodide-rich diet, but its pathogenic role remains unclear. The effects of excessive iodine on TRAIL and its death receptor expression in thyroid were investigated. Experimental autoimmune thyroiditis (EAT) was induced by excessive iodine and thyroglobulin (Tg) in non-obese diabetic mice. The expression of TRAIL and its death receptor DR5 was detected by immunofluorescence staining. Following administration of excessive iodine alone, Tg, and excessive iodine combined with Tg, TRAIL-positive cells appear not only in follicular cells but also in lymphocytes infiltrated in the thyroid, whereas DR5-positive cells appear only in follicular cells. Large numbers of CD3-positive cells and a few CD22-positive cells were detected in thyroid. A great amount of follicular cells were labeled specifically by terminal deoxynucleotide transferase-mediated deoxynucleotide triphosphate nick-end labeling assay. Taken together, our results suggest that excessive iodine could induce TRAIL and DR5 abnormal expression in thyroid. TRAIL band with DR5 to promote follicular cells apoptosis thus mediate thyroid destruction in EAT.

  6. Levodopa-induced dyskinesias in tyrosine hydroxylase deficiency.

    PubMed

    Pons, Roser; Syrengelas, Dimitris; Youroukos, Sotiris; Orfanou, Irene; Dinopoulos, Arqirios; Cormand, Bru; Ormazabal, Aida; Garzía-Cazorla, Angels; Serrano, Mercedes; Artuch, Rafael

    2013-07-01

    The objective of this study was to characterize levodopa (l-dopa)-induced dyskinesias in patients with tyrosine hydroxylase deficiency. Clinical observation was carried out on 6 patients who were diagnosed with tyrosine hydroxylase deficiency and were treated with escalating doses of l-dopa. All 6 patients showed l-dopa-induced dyskinesias of variable intensity early in the course of treatment and regardless of the age of initiation. l-Dopa-induced dyskinesias were precipitated by increases in the dose of l-dopa and also by febrile illnesses and stress. They caused dysfunction and distress in 2 patients. The dyskinesias were improved by decreasing the l-dopa dose or by slowing its titration upward. Increasing the dose frequency was helpful in 2 patients, and introducing amantadine was helpful in another 2 patients. l-Dopa-induced dyskinesias are a common phenomenon in tyrosine hydroxylase deficiency. The current observations show that l-dopa-induced dyskinesias are frequent in a dopamine-deficient state in the absence of nigrostriatal degeneration. Although l-dopa-induced dyskinesias in tyrosine hydroxylase deficiency are phenomenologically similar to those that occur in Parkinson's disease, they are different in a number of other respects, suggesting intrinsic differences in the pathophysiologic basis of l-dopa-induced dyskinesias in the 2 conditions. © 2013 Movement Disorder Society.

  7. Crack initiation and propagation behavior of zirconium cladding under an environment of iodine-induced stress corrosion

    NASA Astrophysics Data System (ADS)

    Park, Sang Yoon; Kim, Jun Hwan; Choi, Byung Kwon; Jeong, Yong Hwan

    2007-04-01

    Tests of iodine-induced stress corrosion cracking (ISCC) were carried out to elucidate the initiation and propagation of cracks in the claddings of zirconium alloys. Zircaloy-4 cladding and Nb-contained zirconium cladding were pressurized with and without a pre-cracked state at 350°C in an iodine environment. The results show that pitting nucleation and growth play an important role in initiating ISCC. Pits preferentially grow and agglomerate around the grain boundary, where the number of pits increases with the iodine concentration and the hoop stress of the claddings. A model of grain-boundary pitting coalescence and a model of pitting-assisted slip cleavage, which were proposed to clearly elucidate the crack initiation and propagation process under ISCC, produce reasonable results. The Nb-contained zirconium cladding exhibits higher ISCC resistance than Zircaloy-4 from the standpoint of a higher threshold stress-intensity factor and a lower crack propagation rate.

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

    PubMed

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

    2016-01-01

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

  9. 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.

  10. 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.

  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. Determination of discretionary salt intake in an iodine deficient area of East Java-Indonesia using three different methods.

    PubMed

    Mustafa, Annasari; Muslimatun, Siti; Untoro, Juliawati; Lan, Maria C P J; Kristianto, Yohanes

    2006-01-01

    As salt is a potential vehicle for delivering iodine to a population, study on salt intake is important. Many methods have been used to measure iodised-salt intake, but the methods were suspected to be inaccurate. A new method, called a lithium-marker technique, has been considered as suitable and safe; hence it has been proposed as a gold standard for measuring the actual salt intake of an individual. We conducted a study to determine discretionary salt intake using the lithium marker technique. The study shows that the total salt intake for children (N = 15) and mothers (N = 15) were 5.4+/-2.1 g/d and 5.8+/-1.7 g/d respectively in which 48.5+/-17.1% and 50.5?17.3% were discretionary salt. The discretionary salt intake measured using lithium marker (2.53 +/- 1.2 g/d for children and 2.99 +/- 1.5 g/d for mother) were significantly lower than using 24-hour salt recall (7.01+/-2.44 g/cap/d) and salt weighing (6.00+/-1.8 g/cap/d) (p<0.001). In conclusion, the discretionary salt intake by 24-hour salt recall and salt weighing were over estimated as compared to the lithium-labelled salt measurement. It is recommended that the level of iodine fortification in salt be increased up to 80-100 ppm of KIO3 to provide iodine intake of 150 microg/d.

  13. Testis damage induced by zinc deficiency in rats.

    PubMed

    Merker, H J; Günther, T

    1997-04-01

    Male Wistar rats were fed a Zn-deficient diet (1.2 mg/kg of Zn) for 28 days. Testes were then studied by light and electron microscopy. Zn deficiency induced necroses of precursors of germ cells leading to tubular atrophy and affected differentiation of spermatids. This was expressed by the occurrence of 2-4 axoneme-dense fibre-mitochondria complexes in one spermatid. Moreover, outer dense fibres, which normally contain 90% of sperm Zn, were "uncoiled" and flattened. The multiplication of the axoneme-dense fibre-mitochondria complexes induced by Zn deficiency might have been produced by an increase of Fe in spermatids and an increased formation of oxygen free radicals.

  14. The role of iodine in human growth and development.

    PubMed

    Zimmermann, Michael B

    2011-08-01

    Iodine is an essential component of the hormones produced by the thyroid gland. Thyroid hormones, and therefore iodine, are essential for mammalian life. Iodine deficiency is a major public health problem; globally, it is estimated that two billion individuals have an insufficient iodine intake. Although goiter is the most visible sequelae of iodine deficiency, the major impact of hypothyroidism due to iodine deficiency is impaired neurodevelopment, particularly early in life. In the fetal brain, inadequate thyroid hormone impairs myelination, cell migration, differentiation and maturation. Moderate-to-severe iodine deficiency during pregnancy increases rates of spontaneous abortion, reduces birth weight, and increases infant mortality. Offspring of deficient mothers are at high risk for cognitive disability, with cretinism being the most severe manifestation. It remains unclear if development of the offspring is affected by mild maternal iodine deficiency. Moderate-to-severe iodine deficiency during childhood reduces somatic growth. Correction of mild-to-moderate iodine deficiency in primary school aged children improves cognitive and motor function. Iodine prophylaxis of deficient populations with periodic monitoring is an extremely cost effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle.

  15. 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.

  16. Bovine monocyte-derived macrophage function in induced copper deficiency.

    PubMed

    Cerone, S; Sansinanea, A; Streitenberger, S; García, C; Auza, N

    2000-03-01

    The effect of molybdenum-induced copper deficiency on monocyte-derived macrophage function was examined. Five female calves were given molybdenum (30 ppm) and sulphate (225 ppm) to induce experimental secondary copper deficiency. Oxidant production by bovine macrophages was measured after stimulation with phorbol myristate acetate (PMA) and opsonized zymosan (OpZ). Lipoperoxidative effects inside of macrophage, superoxide dismutase activity, superoxide anion and hydrogen peroxide formation were determined. Copper deficiency was confirmed from decreased serum copper levels, and animals with values less than 5.9 micromol/l were considered deficient. The content of intracellular copper decreased about 40% in deficient cells compared with the controls. The respiratory burst activity determined by nitroblue tetrazolium reduction was significantly impaired with both stimulants used. Superoxide anion formation was less affected than hydrogen peroxide generation. In addition, increased lipid peroxidation was observed. It could be concluded that the effect of these changes may impair the monocyte-derived macrophage function in the immune system.

  17. 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

  18. 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

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

    PubMed

    Vanderpump, Mark

    2014-12-01

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

  20. Accelerated degradation of methylammonium lead iodide perovskites induced by exposure to iodine vapour

    NASA Astrophysics Data System (ADS)

    Wang, Shenghao; Jiang, Yan; Juarez-Perez, Emilio J.; Ono, Luis K.; Qi, Yabing

    2017-01-01

    Efficiencies of organic-inorganic lead halide perovskite solar cells (PSCs) have significantly increased in recent years, but instability issues impede their further development and application. Previous studies reported that volatile species (for example, iodine, I2) were generated when perovskites were subjected to moisture, oxygen, light illumination, applied electric field, and thermal stress (all of which are relevant to the operation of PSCs in practical applications). Here we show that I2 vapour causes severe degradation of MAPbI3 (MA: CH3NH3+) perovskite, due to chemical chain reactions. Furthermore, I2 vapour could also induce degradation of other iodide-based perovskites, such as FAPbI3 (FA: HC(NH2)2+) and FA0.8Cs0.2PbI3. The results reveal a universal degradation factor for iodide-based perovskite by I2. As the release of I2 is nearly inevitable during practical applications, this work suggests that MAPbI3 may not be suitable for long-term stable solar cells and it is imperative to develop other types of perovskite material to achieve stable PSCs.

  1. 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.

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

    PubMed

    Alkhuja, Samer; Pyram, Ronald; Odeyemi, Olutunde

    2013-01-01

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

  3. Iodine poisoning

    MedlinePlus

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

  4. Calnexin deficiency and endoplasmic reticulum stress-induced apoptosis.

    PubMed

    Zuppini, Anna; Groenendyk, Jody; Cormack, Lori A; Shore, Gordon; Opas, Michal; Bleackley, R Chris; Michalak, Marek

    2002-02-26

    In this study, we used calnexin-deficient cells to investigate the role of this protein in ER stress-induced apoptosis. We found that calnexin-deficient cells are relatively resistant to ER stress-induced apoptosis. However, caspase 3 and 8 cleavage and cytochrome c release were unchanged in these cells, indicating that ER to mitochondria "communication" during apoptotic stimulation is not affected in the absence of calnexin. The Bcl-2:Bax ratio was also not significantly changed in calnexin-deficient cells regardless of whether the ER stress was induced with thapsigargin or not. Ca(2+) homeostasis and ER morphology were unaffected by the lack of calnexin, but ER stress-induced Bap31 cleavage was significantly inhibited. Immunoprecipitation experiments revealed that Bap31 forms complexes with calnexin, which may play a role in apoptosis. The results suggest that calnexin may not play a role in the initiation of the ER stress but that the protein has an effect on later apoptotic events via its influence on Bap31 function.

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

    SciTech Connect

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

    1985-12-01

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

  6. Formate Dehydrogenase, an Enzyme of Anaerobic Metabolism, Is Induced by Iron Deficiency in Barley Roots1

    PubMed Central

    Suzuki, Kazuya; Itai, Reiko; Suzuki, Koichiro; Nakanishi, Hiromi; Nishizawa, Naoko-Kishi; Yoshimura, Etsuro; Mori, Satoshi

    1998-01-01

    To identify the proteins induced by Fe deficiency, we have compared the proteins of Fe-sufficient and Fe-deficient barley (Hordeum vulgare L.) roots by two-dimensional polyacrylamide gel electrophoresis. Peptide sequence analysis of induced proteins revealed that formate dehydrogenase (FDH), adenine phosphoribosyltransferase, and the Ids3 gene product (for Fe deficiency-specific) increased in Fe-deficient roots. FDH enzyme activity was detected in Fe-deficient roots but not in Fe-sufficient roots. A cDNA encoding FDH (Fdh) was cloned and sequenced. Fdh expression was induced by Fe deficiency. Fdh was also expressed under anaerobic stress and its expression was more rapid than that induced by Fe deficiency. Thus, the expression of Fdh observed in Fe-deficient barley roots appeared to be a secondary effect caused by oxygen deficiency in Fe-deficient plants. PMID:9489019

  7. CHOP deficiency inhibits methylglyoxal-induced endothelial dysfunction.

    PubMed

    Choi, Yoon Young; Kim, Suji; Han, Jung-Hwa; Nam, Dae-Hwan; Park, Kwon Moo; Kim, Seong Yong; Woo, Chang-Hoon

    2016-11-18

    Epidemiological studies suggested that diabetic patients are susceptible to develop cardiovascular complications along with having endothelial dysfunction. It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction rather than glucose itself. Here, we investigated the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress. Biochemical data showed that 4-PBA significantly inhibited MGO-induced protein cleavages of PARP-1 and caspase-3. In addition, it was found that high glucose-induced endothelial apoptosis was enhanced in the presence of GLO1 inhibitor, suggesting the role of endogenous MGO in high glucose-induced endothelial dysfunction. MGO-induced endothelial apoptosis was significantly diminished by the depletion of CHOP with si-RNA against human CHOP, but not by SP600125, a specific inhibitor of JNK. The physiological relevance of this signaling pathway was demonstrated in CHOP deficiency mouse model, in which instillation of osmotic pump containing MGO led to aortic endothelial dysfunction. Notably, the aortic endothelial dysfunction response to MGO infusion was significantly improved in CHOP deficiency mice compared to littermate control. Taken together, these findings indicate that MGO specifically induces endothelial dysfunction in a CHOP-dependent manner, suggesting the therapeutic potential of CHOP inhibition in diabetic cardiovascular complications.

  8. 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.

  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. Simultaneous multiple-point velocity measurements using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Mcdaniel, J. C.; Hiller, B.; Hanson, R. K.

    1983-01-01

    A technique is demonstrated for measuring velocity at multiple locations in a plane of a gaseous flowfield using Doppler-shifted absorption with fluorescence detection from iodine molecules, excited by a sheet of tunable single-axial-mode argon-ion laser radiation at 514.5 nm. Measurements were made simultaneously at 10,000 points in an iodine-seeded supersonic flow field with a 100 x 100 element photodiode array camera and were found to agree well with a numerical solution for the velocity field. The accuracy with which a component of velocity can be measured is limited, in the current approach, by the iodine linewidth to about 5 m/sec.

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

    PubMed

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

    2010-09-01

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

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

    PubMed

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

    2015-01-29

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

  13. Iodine biofortification of crops: agronomic biofortification, metabolic engineering and iodine bioavailability.

    PubMed

    Gonzali, Silvia; Kiferle, Claudia; Perata, Pierdomenico

    2016-10-27

    Iodine deficiency is a widespread micronutrient malnutrition problem, and the addition of iodine to table salt represents the most common prophylaxis tool. The biofortification of crops with iodine is a recent strategy to further enrich the human diet with a potentially cost-effective, well accepted and bioavailable iodine source. Understanding how iodine functions in higher plants is key to establishing suitable biofortification approaches. This review describes the current knowledge regarding iodine physiology in higher plants, and provides updates on recent agronomic and metabolic engineering strategies of biofortification. Whereas the direct administration of iodine is effective to increase the iodine content in many plant species, a more sophisticated genetic engineering approach seems to be necessary for the iodine biofortification of some important staple crops.

  14. Effects of Increased Iodine Intake on Thyroid Disorders

    PubMed Central

    Sun, Xin; Shan, Zhongyan

    2014-01-01

    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

  15. Galerkin analysis of light-induced patterns in the chlorine dioxide-iodine-malonic acid reaction-diffusion system

    NASA Astrophysics Data System (ADS)

    Ghosh, Pushpita; Sen, Shrabani; Riaz, Syed Shahed; Ray, Deb Shankar

    2009-05-01

    The photosensitive chlorine dioxide-iodine-malonic acid reaction-diffusion system has been an experimental paradigm for the study of Turing pattern over the last several years. When subjected to illumination of varied intensity by visible light the patterns undergo changes from spots to stripes, vice versa, and their mixture. We carry out a nonlinear analysis of the underlying model in terms of a Galerkin scheme with finite number of modes to explore the nature of the stability and existence of various modes responsible for the type and crossover of the light-induced patterns.

  16. Quantitative measurement of transverse injector and free stream interaction in a nonreacting SCRAMJET combustor using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

    A preliminary quantitative study of the compressible flowfield in a steady, nonreacting model SCRAMJET combustor using laser-induced iodine fluorescence (LIIF) is reported. Measurements of density, temperature, and velocity were conducted with the calibrated, nonintrusive, optical technique for two different combustor operating conditions. First, measurements were made in the supersonic flow over a rearward-facing step without transverse injection for comparison with calculated pressure profiles. The second configuration was staged injection behind the rearward-facing step at an injection dynamic pressure ratio of 1.06. These experimental results will be used to validate computational fluid dynamic (CFD) codes being developed to model supersonic combustor flowfields.

  17. 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.

  18. Contact Lens-induced Limbal Stem Cell Deficiency.

    PubMed

    Rossen, Jennifer; Amram, Alec; Milani, Behrad; Park, Dongwook; Harthan, Jennifer; Joslin, Charlotte; McMahon, Timothy; Djalilian, Ali

    2016-10-01

    Limbal stem cell deficiency (LSCD) is a pathologic condition caused by the dysfunction and/or destruction of stem cell precursors of the corneal epithelium, typified clinically by corneal conjunctivalization. The purpose of this review is to critically discuss a less well-known cause of limbal stem cell disease: contact lens (CL) wear. A literature search was conducted to include original articles containing patients with CL-induced LSCD. This review describes epidemiology, diagnostic strategies, pathogenesis, differential diagnosis, and treatment modalities for this condition.

  19. Susceptibility to cerulein-induced pancreatitis in inducible nitric oxide synthase-deficient mice.

    PubMed

    Qui, B; Mei, Q B; Ma, J J; Korsten, M A

    2001-07-01

    Production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been proposed as a pathogenic factor in acute pancreatitis, but its role has still not been fully examined. The present study explored the role of iNOS in cerulein-induced acute pancreatitis using iNOS-deficient mice. Twelve- to 14-week-old male mice (C57B1/6 and iNOS-deficient) were administered cerulein by intraperitoneal (i.p.) injection at hourly intervals for 7 hours and killed 24 hours later after the first dose. Pancreatic wet weight, pancreatic myeloperoxidase (MPO) activity, and levels of plasma nitrite and serum amylase were measured. In another experiment isosorbide dinitrate (an NO donor) was given by oral gavage every 6 hours for 24 hours beginning simultaneously with cerulein injections in iNOS-deficient mice. Cerulein administration dose-dependently increased pancreatic wet weight, myeloperoxidase activity, and levels of nitrite and amylase in C57B1/6 mice. These parameters (except nitrite levels) were significantly intensified in iNOS-deficient mice. At the dose employed, cerulein failed to increase nitrite levels in iNOS-deficient mice. The susceptibility to cerulein toxicity in iNOS-deficient mice was abolished by NO donor treatment. NO release from an iNOS source appears to play a protective role in cerulein-induced pancreatitis. At least in part, NO may prevent neutrophil accumulation after cerulein administration.

  20. NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes

    PubMed Central

    Das, Archita; Dey, Neekkan; Ghosh, Arunava; Das, Tanusree; Chatterjee, Indu B.

    2011-01-01

    Background The etiology of myelodysplastic syndromes (MDS) is largely unknown. Exposure to cigarette smoke (CS) is reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(P)H-quinone: oxidoreductase 1 (NQO1) increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin C deficiency might produce MDS in CS-exposed guinea pigs. Methodology and Principal Findings Here we show that CS exposure for 21 days produces MDS in guinea pigs having deficiency of NQO1 (fed 3 mg dicoumarol/day) conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day). As evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory cytopenia with unilineage dysplasia (RCUD): refractory anemia; refractory thrombocytopenia that is associated with ring sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+) cells and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS vitamin C becomes ineffective. Conclusions and Significance CS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS. PMID:21655231

  1. 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.

  2. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    SciTech Connect

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

    2015-09-15

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

  3. 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.

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

    PubMed

    2007-07-02

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

  5. Dissecting iron deficiency-induced proton extrusion in Arabidopsis roots.

    PubMed

    Santi, Simonetta; Schmidt, Wolfgang

    2009-01-01

    Here, we have analysed the H(+)-ATPase-mediated extrusion of protons across the plasma membrane (PM) of rhizodermic cells, a process that is inducible by iron (Fe) deficiency and thought to serve in the mobilization of sparingly soluble Fe sources. The induction and function of Fe-responsive PM H(+)-ATPases in Arabidopsis roots was investigated by gene expression analysis and by using mutants defective in the expression or function of one of the isogenes. In addition, the expression of the most responsive isogenes was investigated in natural Arabidopsis accessions that have been selected for their in vivo proton extrusion activity. Our data suggest that the rhizosphere acidification in response to Fe deficiency is chiefly mediated by AHA2, while AHA1 functions as a housekeeping isoform. The aha7 knock-out mutant plants showed a reduced frequency of root hairs, suggesting an involvement of AHA7 in the differentiation of rhizodermic cells. Acidification capacity varied among Arabidopsis accessions and was associated with a high induction of AHA2 and IRT1, a high relative growth rate and a shoot-root ratio that was unaffected by the external Fe supply. An effective regulation of the Fe-responsive genes and a stable shoot-root ratio may represent important characteristics for the Fe uptake efficiency.

  6. Paradoxical glucose-induced hyperkalemia. Combined aldosterone-insulin deficiency.

    PubMed

    Goldfarb, S; Strunk, B; Singer, I; Goldberg, M

    1975-11-01

    Severe hyperkalemia associated with spontaneous hyperglycemia as well as with the intravenous infusions of glucose occurred in an insulin-requiring diabetic patient in the absence of potassium administration, the use of diuretics which inhibit urinary potassium excretion or acidemia. Metabolic balance studies revealed, in addition to diabets, the presence of isolated aldosterone deficiency of the hyporeninemic type. Intravenous glucose infusions (0.5 g/kg body weight) produced significant hyperkalemia but desoxycortisone acetate (DOCA) therapy (10 mg/day) prevented the glucose-induced hyperkalemia. In this patient, the serum potassium concentration increases after the intravenous infusions of glucose because there is insufficient aldosterone and insulin to reverse the transfer of potassium to the extracellular fluid which normally occurs after hypertonic infusions of glucose. Although DOCA replacement modifies the distribution of potassium in the extracellular fluid and blunts the hyperkalemic effect of intravenous infusions of glucose, a rise in the insulin level is required for the usual hypokalemic response to intravenously administered glucose. These studies illustrate the risk of raising blood glucose levels in patients with combined aldosterone and insulin deficiency and the tendency towards hyperkalemia in diabetic patients under certain clinical conditions.

  7. A Ground-Based Instrument for the Laser-Induced Fluorescence Detection of Coastal Iodine Monoxide (IO)

    NASA Astrophysics Data System (ADS)

    Hannun, R. A.; Thurlow, M. E.; O'Brien, A.; Co, D. T.; Hanisco, T. F.; Lapson, L. B.; Anderson, J.

    2011-12-01

    The photochemistry of iodine monoxide (IO) within the marine boundary layer plays a role in the catalytic loss cycles of surface ozone and potentially leads to the nucleation of marine aerosols. Biogenic emissions of molecular iodine and organo-halide precursor molecules account for the largest sources of IO in marine and coastal environments. Due to the inhomogeneous distribution of atmospheric IO in conjunction with low mixing ratios of less than 10 ppt, high sensitivity in-situ measurements are needed in order to better understand the impact of IO photochemistry in a quantifiable way. To address these challenges, a laser-induced fluorescence instrument has been developed, with a nanosecond-pulsed Nd:YAG-pumped Ti:Sapphire laser system. Through efficient optical design and fluorescence detection, we are able to operate in the sensitivity threshold of 1 ppt per minute for IO. Further design considerations included the development of a mobile, weatherproof instrument configuration, which can sustain deployment in a variety of field conditions. In order to validate the detection technique, the instrument was deployed at Shoals Marine Laboratory in Maine from August-September 2011. Instrument design considerations as well as preliminary results of the detection of IO from laminaria digitata, a kelp species present in coastal New England sites, will be presented.

  8. The way forward in Italy for iodine.

    PubMed

    Olivieri, Antonella; DI Cosmo, Caterina; DE Angelis, Simona; DA Cas, Roberto; Stacchini, Paolo; Pastorelli, Augusto; Vitti, Paolo

    2017-04-01

    Italy is dealing with iodine deficiency since ancient times. In 1848 an ad hoc committee appointed by the king of Sardinia, identified extensive areas afflicted by endemic goiter and endemic cretinism in Piedmont, Liguria and Sardinia. Since then many epidemiological studies have been conducted in our country. These showed that iodine deficiency was present not only in mountain areas but also in coastal areas. In 1972 the iodization of salt at 15 mg/kg was allowed by law and iodized salt was distributed on request to selected endemic areas. Five years later the distribution was extended to the whole country. However the sale of iodized salt was not mandatory at that time and only a small fraction of the Italian population started using iodized salt. In 1991 the content of iodine in the salt was raised to 30 mg/kg and in 2005 a nationwide salt iodization program was finally implemented. Some years later a nationwide monitoring program of iodine prophylaxis was also implemented. Since 2005 the sale of iodized salt in Italian supermarkets has increased (34% in 2006, 55% in 2012), although it has been observed that the use of iodized salt is still low in the communal eating areas and in the food industry. These data are coherent with recent epidemiological studies showing that some regions in our country are still characterized by mild iodine deficiency and a high frequency of goiter and other iodine deficiency disorders. This implies that further efforts should be made to successfully correct iodine deficiency in Italy.

  9. 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.

  10. [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.

  11. Amelioration of estrogen deficiency-induced obesity by collagen hydrolysate

    PubMed Central

    Chiang, Tsay-I; Chang, I-Chang; Lee, Hsueh-Hui; Hsieh, Kuang hui; Chiu, Yung-Wei; Lai, Te-Jen; Liu, Jer-Yuh; Hsu, Li-Sung; Kao, Shao-Hsuan

    2016-01-01

    Objectives: Menopausal transition with declining estrogen levels significantly affects the physiological properties of women and consequently contributes to a series of medical conditions, including obesity. Obesity is a crucial risk factor associated with cardiovascular diseases, diabetes mellitus, and breast cancer. Increasing dietary protein content improves satiety and energy expenditure. Thus, we hypothesize that supplementing with collagen, a common dietary protein, may alleviate menopause-induced obesity. Methods: We used ovariectomized (OVX) rats to mimic a menopausal human. The body weight of OVX rats significantly increased compared with that of sham-operated rats (P<0.05), but uterus weight was decreased. Adipocyte size in perigonadal adipose tissue also increased (P<0.05). Results: By contrast, OVX rats supplemented with aqueous collagen hydrolysate (2.5 mg/mL) exhibited significant attenuation in body weight gain and adipocyte enlargement (P<0.05), but insignificant change in uterus weight. Further investigation indicated that collagen hydrolysate supplementation insignificantly affected the levels of dorsal fat, serum total cholesterol, and serum triacylglycerol. Levels of serum biochemical factors, calcium, phosphorus, and glucose were also insignificantly altered by collagen hydrolysate supplementation. Conclusion: Collagen hydrolysate supplementation reduced body weight gain and adipocyte enlargement in response to ovariectomy but slightly affected blood lipids, calcium, and glucose in both sham-operated and OVX rats. Collagen hydrolysate supplementation is beneficial in ameliorating estrogen deficiency-induced obesity and its associated risk factors. PMID:27877077

  12. Amelioration of estrogen deficiency-induced obesity by collagen hydrolysate.

    PubMed

    Chiang, Tsay-I; Chang, I-Chang; Lee, Hsueh-Hui; Hsieh, Kuang Hui; Chiu, Yung-Wei; Lai, Te-Jen; Liu, Jer-Yuh; Hsu, Li-Sung; Kao, Shao-Hsuan

    2016-01-01

    Objectives: Menopausal transition with declining estrogen levels significantly affects the physiological properties of women and consequently contributes to a series of medical conditions, including obesity. Obesity is a crucial risk factor associated with cardiovascular diseases, diabetes mellitus, and breast cancer. Increasing dietary protein content improves satiety and energy expenditure. Thus, we hypothesize that supplementing with collagen, a common dietary protein, may alleviate menopause-induced obesity. Methods: We used ovariectomized (OVX) rats to mimic a menopausal human. The body weight of OVX rats significantly increased compared with that of sham-operated rats (P<0.05), but uterus weight was decreased. Adipocyte size in perigonadal adipose tissue also increased (P<0.05). Results: By contrast, OVX rats supplemented with aqueous collagen hydrolysate (2.5 mg/mL) exhibited significant attenuation in body weight gain and adipocyte enlargement (P<0.05), but insignificant change in uterus weight. Further investigation indicated that collagen hydrolysate supplementation insignificantly affected the levels of dorsal fat, serum total cholesterol, and serum triacylglycerol. Levels of serum biochemical factors, calcium, phosphorus, and glucose were also insignificantly altered by collagen hydrolysate supplementation. Conclusion: Collagen hydrolysate supplementation reduced body weight gain and adipocyte enlargement in response to ovariectomy but slightly affected blood lipids, calcium, and glucose in both sham-operated and OVX rats. Collagen hydrolysate supplementation is beneficial in ameliorating estrogen deficiency-induced obesity and its associated risk factors.

  13. Interleukin-17A deficiency ameliorates streptozotocin-induced diabetes.

    PubMed

    Tong, Zan; Liu, Weihuang; Yan, Huichao; Dong, Chen

    2015-10-01

    Interleukin-17 (IL-17) is a cytokine with critical functions in multiple autoimmune diseases. However, its roles in type I diabetes and the underlying mechanisms remain to be fully elucidated. In the current study, we investigated the impact of IL-17 deficiency on streptozotocin (STZ) -induced diabetes. Il-17(-/-) mice exhibited attenuated hyperglycaemia and insulitis after STZ treatment compared with control mice. The Il-17(-/-) mice had fewer CD8(+) cells infiltrating the pancreas than wild-type controls after STZ injection. Wild-type mice showed increased percentage and number of splenic CD8(+) cells and decreased Gr1(+)  CD11b(+) myeloid-derived suppressor cells (MDSC) after STZ treatment, but Il-17(-/-) mice maintained the percentages and numbers of splenic CD8(+) cells and MDSC, suggesting that IL-17 is implicated in STZ-induced cellular immune responses in the spleen. We further purified the MDSC from spleens of STZ-treated mice. Il-17(-/-) MDSC showed increased ability to suppress CD8(+) cell proliferation in vitro compared with wild-type MDSC. Transfer of MDSC to diabetic mice showed that MDSC from Il-17(-/-) mice could ameliorate hyperglycaemia. Moreover, recipients with MDSC from Il-17(-/-) mice had a decreased percentage of CD8(+) cell in the spleen compared with recipients with MDSC from wild-type mice. These data suggest that IL-17 is required in splenic MDSC function after STZ delivery. In summary, our study has revealed a pathogenic role of IL-17 in an STZ-induced diabetes model with important implications for our understanding of IL-17 function in autoimmune diseases.

  14. 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.

  15. 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%).

  16. 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.

  17. RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

    PubMed Central

    Arikkatt, Jaisy; Ullah, Md Ashik; Short, Kirsty Renfree; Zhang, Vivan; Gan, Wan Jun; Loh, Zhixuan; Werder, Rhiannon B; Simpson, Jennifer; Sly, Peter D; Mazzone, Stuart B; Spann, Kirsten M; Ferreira, Manuel AR; Upham, John W; Sukkar, Maria B; Phipps, Simon

    2017-01-01

    Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target. DOI: http://dx.doi.org/10.7554/eLife.21199.001 PMID:28099113

  18. Nitrous oxide–induced vitamin B12 deficiency

    PubMed Central

    Simonsen, Cameron; Seago, Susan

    2017-01-01

    Nitrous oxide is a gas that is odorless, colorless, and has a sweet taste at room temperature. Nitrous oxide has several uses, including in surgery and dentistry (referred to as “laughing gas”), in automotive racing, and in aerosol spray propellants. The aerosol spray propellants that typically use nitrous oxide are whipped cream canisters and cooking sprays. Unfortunately, these over-the-counter household items are a source of nitrous oxide that can be used for recreational use. The most popular is the use of industrial-grade canisters having the slang term “whippets.” The nitrous oxide can be extracted by pushing the nozzle down slightly to the side and catching the released gas with a balloon. The contents of the balloon can then be directly inhaled, giving an instant feeling of euphoria. This is not a benign means to achieve a euphoric state but can cause severe nitrous oxide–induced B12 deficiency, which is presented in this case report.

  19. Glucocorticoid-Induced Osteoporosis in Children with 21-Hydroxylase Deficiency

    PubMed Central

    Ventura, Annamaria; Brunetti, Giacomina; Colucci, Silvia; Oranger, Angela; Ladisa, Filomena; Cavallo, Luciano; Grano, Maria; Faienza, Maria Felicia

    2013-01-01

    21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD. PMID:23484098

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

    PubMed

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

    2014-05-01

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

  1. Modelling primaquine-induced haemolysis in G6PD deficiency

    PubMed Central

    Watson, James; Taylor, Walter RJ; Menard, Didier; Kheng, Sim; White, Nicholas J

    2017-01-01

    Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent. DOI: http://dx.doi.org/10.7554/eLife.23061.001 PMID:28155819

  2. Glucocorticoid-induced osteoporosis in children with 21-hydroxylase deficiency.

    PubMed

    Ventura, Annamaria; Brunetti, Giacomina; Colucci, Silvia; Oranger, Angela; Ladisa, Filomena; Cavallo, Luciano; Grano, Maria; Faienza, Maria Felicia

    2013-01-01

    21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD.

  3. 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

  4. 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.

  5. Helicobacter cinaedi Induced Typhlocolitis in Rag-2-Deficient Mice

    PubMed Central

    Shen, Zeli; Feng, Yan; Rickman, Barry; Fox, James G.

    2015-01-01

    Background Helicobacter cinaedi, an enterohepatic helicobacter species (EHS), is an important human pathogen and is associated with a wide range of diseases, especially in immunocompromised patients. It has been convincingly demonstrated that innate immune response to certain pathogenic enteric bacteria is sufficient to initiate colitis and colon carcinogenesis in recombinase-activating gene (Rag)-2-deficient mice model. To better understand the mechanisms of human IBD and its association with development of colon cancer, we investigated whether H. cinaedi could induce pathological changes noted with murine enterohepatic helicobacter infections in the Rag2−/− mouse model. Materials and Methods Sixty 129SvEv Rag2−/− mice mouse were experimentally or sham infected orally with H. cinaedi strain CCUG 18818. Gastrointestinal pathology and immune responses in infected and control mice were analyzed at 3, 6 and 9 months postinfection (MPI). H. cinaedi colonized the cecum, colon, and stomach in infected mice. Results H. cinaedi induced typhlocolitis in Rag2−/− mice by 3 MPI and intestinal lesions became more severe by 9 MPI. H. cinaedi was also associated with the elevation of proinflammatory cytokines, interferon-γ, tumor-necrosis factor-α, IL-1β, IL-10; iNOS mRNA levels were also upregulated in the cecum of infected mice. However, changes in IL-4, IL-6, Cox-2, and c-myc mRNA expressions were not detected. Conclusions Our results indicated that the Rag2−/− mouse model will be useful to continue investigating the pathogenicity of H. cinaedi, and to study the association of host immune responses in IBD caused by EHS. PMID:25381744

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

    PubMed

    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.

  7. Biologically available iodine in goitrogenic diets

    SciTech Connect

    Van Middlesworth, L.

    1985-01-01

    Eight different sources of low-iodine diet (LID) were tested in mice over 14 years. The available iodine in each diet was measured by isotopic equilibration. Commercially prepared Remington diets contained 6.8 to 69.3 ng available iodine/g, and the results were usually different from shipment to shipment. Some samples produced greatly enlarged thyroids. The Remington diets from two sources were occasionally low in iodine but produced little thyroid enlargement. Between 1977 and 1980 only one shipment of Remington diet was found to contain less than 10 ng available I/g, and it resulted in large goiters. Since 1980 other compositions of LID have been used, but they caused additional abnormalities during breeding or chronic feeding. A low-iodine wheat diet produced goiter in mice more readily than in rats. In the course of testing for unavailable forms of dietary iodine, it was found that only 34.2% of thyroxine iodine was available to the thyroid iodine pool of mice. It is concluded that unidentified nutritional deficiency or dietary contaminants can alter the goitrogenic response to restricted iodine intake. Furthermore, at least one natural form of potential dietary iodine is incompletely available to mice.

  8. 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...

  9. 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

  10. 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

  11. Deficiency of the Bax gene attenuates denervation-induced apoptosis

    PubMed Central

    Siu, P. M.; Alway, S. E.

    2015-01-01

    Apoptosis has been implicated in mediating denervation-induced muscle wasting. In this study we determined the effect of interference of apoptosis on muscle wasting during denervation by using mice genetically deficient in pro-apoptotic Bax. After denervation, muscle wasting was evident in both wild-type and Bax−/− muscles but reduction of muscle weight was attenuated in Bax−/− mice. Apoptotic DNA fragmentation increased in wild-type denervated muscles whereas there was no statistical increase in DNA fragmentation in denervated muscles from Bax−/− mice. Mitochondrial AIF and Smac/DIABLO releases and Bcl-2, p53 and HSP27 increased whereas XIAP and MnSOD decreased to a similar extent in muscles from wild-type and Bax−/− mice following denervation. Mitochondrial cytochrome c release was elevated in denervated muscles from wild-type mice but the increase was suppressed in muscles from Bax−/− mice. Increases in caspase-3 and -9 activities and oxidative stress markers H2O2, MDA/4-HAE and nitrotyrosine were all evident in denervated muscles from wild-type mice but these changes were absent in muscles from Bax−/− mice. Moreover, ARC increased exclusively in denervated Bax−/− muscle. Our data indicate that under conditions of denervation, pro-apoptotic signalling is suppressed and muscle wasting is attenuated when the Bax gene is lacking. These findings suggest that interventions targeting apoptosis may be valuable in ameliorating denervation-associated pathologic muscle wasting in certain neuromuscular disorders that involve partial or full denervation. PMID:16763784

  12. 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...

  13. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part II--vitamin D, vitamin A, iron, zinc, iodine, essential fatty acids.

    PubMed

    Simpson, Joe Leigh; Bailey, Lynn B; Pietrzik, Klaus; Shane, Barry; Holzgreve, Wolfgang

    2011-01-01

    Part II of this review considers additional micronutrients. Vitamin D is a fat soluble vitamin found in foods of animal origins (fatty fish, liver oil) or fortified products (milk, cheese). Vitamin D deficiency is common in African-American women living in northern latitudes. Vitamin D supplementation may be needed to reach desired 25-(OH)D3 concentrations of >50 nmol/L. In foods of animal origin, preformed Vitamin A is present; in plants (fruits and vegetables) vitamin A precursors (β-carotenoids) are present. Vitamin A supplementation is usually not warranted, and in developing countries should not exceed 3000 μg (10,000 IU)/day. Iron in the form of haem-iron is found in meat, fish and poultry; non-haem (inorganic) iron is found in vegetables, fruits and grains. Iron supplementation may be necessary in the third trimester, earlier in pregnancy or in non-pregnant states if serum ferritin is <20 μg/L or haemoglobin <10.9 g/dL. Zinc is available in red meat, seafood including oysters and unpolished grains; supplementation is not necessary. To assure adequate iodine, food is fortified worldwide with iodated salt. If urinary iodine levels are low, supplementation is needed. Essential fatty acids requirements can be met by one to two portions of fish per week.

  14. Optimal buffer gas pressure for laser-induced fluorescence detection of the iodine-129 isotope in the atmosphere

    SciTech Connect

    Kireev, S.V.; Pit`ko, A.V.; Shnyrev, S.L.

    1995-06-01

    The effect of atmospheric air pressure on the intensity of iodine-129 vapor fluorescence excited by a He-Ne (633 nm) laser is studied. It is shown that to achieve the maximum intensity of fluorescence of molecular iodine-129, it is advantageous, first, to use a {sup 3}He-{sup 20}Ne laser for excitation, and second, to detect atmospheric iodine impurities in the gas mixture under analysis evacuated to 2 x 10{sup 18} - 4 x 10{sup 18} mol/cm{sup 3}. In this case, the sensitivity increases about twofold. 7 refs., 4 figs.

  15. 1,25-Vitamin D3 Deficiency Induces Albuminuria.

    PubMed

    Sonneveld, Ramon; Hoenderop, Joost G J; Stavenuiter, Andrea W D; Ferrantelli, Evelina; Baltissen, Marijke P A; Dijkman, Henry B; Florquin, Sandrine; Rops, Angelique L; Wetzels, Jack F M; Berden, Jo H M; van der Vlag, Johan; Nijenhuis, Tom

    2016-04-01

    Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1α-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin-D3-1α-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.

  16. NO synthase-generated NO acts downstream of auxin in regulating Fe-deficiency-induced root branching that enhances Fe-deficiency tolerance in tomato plants

    PubMed Central

    Jin, Chong Wei; Shamsi, Imran Haider; Luo, Bing Fang; Lin, Xian Yong

    2011-01-01

    In response to Fe-deficiency, various dicots increase their root branching which contributes to the enhancement of ferric-chelate reductase activity. Whether this Fe-deficiency-induced response eventually enhances the ability of the plant to tolerate Fe-deficiency or not is still unclear and evidence is also scarce about the signals triggering it. In this study, it was found that the SPAD-chlorophyll meter values of newly developed leaves of four tomato (Solanum lycocarpum) lines, namely line227/1 and Roza and their two reciprocal F1 hybrid lines, were positively correlated with their root branching under Fe-deficient conditions. It indicates that Fe-deficiency-induced root branching is critical for plant tolerance to Fe-deficiency. In another tomato line, Micro-Tom, the increased root branching in Fe-deficient plants was accompanied by the elevation of endogenous auxin and nitric oxide (NO) levels, and was suppressed either by the auxin transport inhibitors NPA and TIBA or the NO scavenger cPTIO. On the other hand, root branching in Fe-sufficient plants was induced either by the auxin analogues NAA and 2,4-D or the NO donors NONOate or SNP. Further, in Fe-deficient plants, NONOate restored the NPA-terminated root branching, but NAA did not affect the cPTIO-terminated root branching. Fe-deficiency-induced root branching was inhibited by the NO-synthase (NOS) inhibitor L-NAME, but was not affected by the nitrate reductase (NR) inhibitor NH4+, tungstate or glycine. Taking all of these findings together, a novel function and signalling pathway of Fe-deficiency-induced root branching is presented where NOS-generated rather than NR-generated NO acts downstream of auxin in regulating this Fe-deficiency-induced response, which enhances the plant tolerance to Fe-deficiency. PMID:21511908

  17. Iodine concentration of organic and conventional milk: implications for iodine intake.

    PubMed

    Bath, Sarah C; Button, Suzanne; Rayman, Margaret P

    2012-04-01

    Iodine is required for adequate thyroid hormone production, which is essential for brain development, particularly in the first trimester of pregnancy. Milk is the principal source of iodine in UK diets, and while small studies in Europe have shown organic milk to have a lower iodine concentration than conventional milk, no such study has been conducted in Britain. In view of the increasing popularity of organic milk in the UK, we aimed to compare the iodine concentration of retail organic and conventional milk and to evaluate regional influences in iodine levels. Samples of organic milk (n 92) and conventional milk (n 80), purchased from retail outlets in sixteen areas of the UK (southern England, Wales and Northern Ireland), were analysed for iodine using inductively coupled plasma MS. The region of origin of the milk was determined from information on the label. Organic milk was 42·1 % lower in iodine content than conventional milk (median iodine concentration 144·5 v. 249·5 ng/g; P < 0·001). There was no difference in the iodine concentration of either conventional or organic milk by area of purchase. However, a difference was seen in iodine concentration of organic milk by region of origin (P < 0·001). The lower iodine concentration of organic milk has public-health implications, particularly in view of emerging evidence of iodine deficiency in UK population sub-groups, including pregnant women. Individuals who choose organic milk should be aware that their iodine intake may be compromised and should ensure adequate iodine intake from alternative sources.

  18. 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.

  19. Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency.

    PubMed Central

    Chan, T K; Todd, D; Tso, S C

    1976-01-01

    People with the variants of glucose-6-phosphate dehydrogenase (GPD) deficiency common in the southern Chinese (Canton, B(-)Chinese, and Hong Kong-Pokfulam) have a moderate shortening of red-cell survival but no anaemia when they are in the steady state. With a cross-transfusion technique, primaquine, nitrofurantoin, and large doses of aspirin were found to aggravate the haemolysis while sulphamethoxazole did so only in some people. Individual differences in drug metabolism may be the reason for this. Many commonly used drugs reported to accentuate haemolysis in GPD deficiency did not shorten red-cell survival. PMID:990860

  20. 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

  1. Radioactive Iodine (Radioiodine) Therapy

    MedlinePlus

    ... and Stage Thyroid Cancer Treating Thyroid Cancer Radioactive Iodine (Radioiodine) Therapy for Thyroid Cancer Your thyroid gland absorbs nearly all of the iodine in your body. When radioactive iodine (RAI), also ...

  2. Iodine in diet

    MedlinePlus

    ... Iodine is needed for the cells to convert food into energy. Humans need iodine for normal thyroid function, and for the production of thyroid hormones. Food Sources Iodized salt is table salt with iodine ...

  3. 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.

  4. Cd-induced Cu deficiency responses in Arabidopsis thaliana: are phytochelatins involved?

    PubMed

    Gielen, Heidi; Vangronsveld, Jaco; Cuypers, Ann

    2017-03-01

    Cadmium (Cd) exposure can disturb the homeostasis of essential elements. In Arabidopsis thaliana, Cd induces a squamosa promoter binding protein-like 7 (SPL7)-dependent Cu deficiency response. We investigated how Cd induces a Cu deficiency response. The Cu deficiency response consists of the active SPL7 transcription factor binding to GTAC motifs in promoters of among others several Cu transporters, a Cu chaperone, and cupro-miRNAs to regulate Cu homeostasis. We demonstrated that the addition of supplemental Cu to Cd-exposed A. thaliana plants diminished the Cu deficiency response in roots, while it even disappeared in leaves. Exposure of plants to Cd in combination with extra Cu reduced Cd levels in both roots and leaves resulting in an improved cellular oxidative state. Furthermore, we demonstrated a role for phytochelatins (PCs) in the Cd-induced Cu deficiency response, because it was reduced in roots of cad1-3 mutant plants exposed to Cd. In conclusion, a working mechanism is provided in which it is suggested that Cd increases PC levels that can complex both Cd and Cu. This results in cellular Cu deficiency and subsequently the activation of SPL7 and hence the induction of the Cu deficiency response.

  5. 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.

  6. Dilated Cardiomyopathy Induced by Chronic Starvation and Selenium Deficiency

    PubMed Central

    2016-01-01

    Protein energy malnutrition (PEM) has been rarely documented as a cause of cardiovascular abnormalities, including dilated cardiomyopathy. Selenium is responsible for antioxidant defense mechanisms in cardiomyocytes, and its deficiency in the setting of PEM and disease related malnutrition (DRM) may lead to exacerbation of the dilated cardiomyopathy. We report a rare case of a fourteen-year-old boy who presented with symptoms of congestive heart failure due to DRM and PEM (secondary to chronic starvation) along with severe selenium deficiency. An initial echocardiogram showed severely depressed systolic function consistent with dilated cardiomyopathy. Aggressive nutritional support and replacement of selenium and congestive heart failure medications that included diuretics and ACE inhibitors with the addition of carvedilol led to normalization of the cardiac function within four weeks. He continues to have significant weight gain and is currently completely asymptomatic from a cardiovascular standpoint. PMID:27994905

  7. Fe deficiency induced changes in rice (Oryza sativa L.) thylakoids.

    PubMed

    Wang, Yuwen; Xu, Chao; Li, Kang; Cai, Xiaojie; Wu, Min; Chen, Guoxiang

    2017-01-01

    Iron deficiency is an important abiotic stress that limits productivity of crops all over the world. We selected a hybrid rice (Oryza sativa L.), LYPJ, which is super high-yield and widely cultured in China, to investigate changes in the components and structure of thylakoid membranes and photosynthetic performance in response to iron deficiency. Our results demonstrated that photosystem I (PSI) is the primary target for iron deficiency, while the changes in photosystem II (PSII) are important for rebuilding a balance in disrupted energy utilization and dissipation caused by differential degradation of photosynthetic components. The result of immunoblot analysis suggested that the core subunit PsaA declined drastically, while PsbA remained relatively stable. Furthermore, several organizational changes of the photosynthetic apparatus were found by BN-PAGE, including a marked decrease in the PSI core complexes, the Cytb 6 /f complex, and the trimeric form of the LHCII antenna, consistent with the observed unstacking grana. The fluorescence induction analysis indicated a descending PSII activity with energy dissipation enhanced markedly. In addition, we proposed that the crippled CO2 assimilation could be compensated by the enhanced of phosphoenolpyruvate carboxylase (PEPC), which is suggested by the decreased ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and photosynthetic efficiency.

  8. Induction of IRT1 by the nickel-induced iron-deficient response in Arabidopsis.

    PubMed

    Nishida, Sho; Aisu, Ayaka; Mizuno, Takafumi

    2012-03-01

    Excessive amounts of nickel (Ni) can be toxic for plants. Recently, we reported that IRT1, the primary iron (Fe) uptake transporter in roots, meditates excess Ni accumulation in Arabidopsis thaliana. We also found that Ni exposure increases IRT1 expression in roots, suggesting that Ni uptake is further induced by Ni stress. Here, we show that Ni exposure induces expression of not only IRT1, but also FRO2, a ferric reductase in the root epidermis, and FIT, a transcription factor regulating the expression of genes involved in Fe homeostasis including IRT1 and FRO2. This result suggests that Ni accumulation induces an Fe-deficient response and leads to the induction of IRT1. Our findings suggest that excess Ni causes Fe deficiency at the molecular level and induces Fe deficiency signaling in plant cells.

  9. 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.

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

    PubMed

    Sun, Zhongjie

    2006-06-01

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

  11. 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.

  12. Protective effects of curcumin against genotoxicity induced by 131-iodine in human cultured lymphocyte cells

    PubMed Central

    Shafaghati, Nayereh; Hedayati, Monireh; Hosseinimehr, Seyed Jalal

    2014-01-01

    Background: 131-radioiodine has been widely used as an effective radionuclide for treatment of patients with thyroid diseases. The purpose of the present study is to investigate the radioprotective effects of curcumin as a natural product that protects against the genotoxic effects of 131I in human cultured lymphocytes. Materials and Methods: Whole blood samples from human volunteers were incubated with curcumin at doses of 5, 10, and 50 μg/mL. After 1-hour incubation, the lymphocytes were incubated with 131I (100 μCi/1.5 ml) for 2 hours. The lymphocyte cultures were then mitogenically stimulated to allow for evaluation of the number of micronuclei in cytokinesis-blocked binucleated cells. Results: Incubation of lymphocytes with 131I at dose 100 μCi/1.5 mL induced genotoxicity shown by increase in micronuclei frequency in human lymphocytes. Curcumin at 5, 10, and 50 μg/mL doses significantly reduced the micronuclei frequency. Maximal protective effects and greatest decrease in micronuclei frequency were observed when whole blood was incubated with 50 μg/mL dose of curcumin with 52%. Conclusion: This study has important implications for patients undergoing 131I therapy. Our results indicate a protective role for curcumin against the genetic damage and side effects induced by 131I administration. PMID:24914274

  13. 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.

  14. Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6 deficiency in rats.

    PubMed

    Kitagawa, Erina; Yamamoto, Tatsuya; Fujishita, Mayuko; Ota, Yuki; Yamamoto, Kohei; Nakagawa, Tomoyuki; Hayakawa, Takashi

    2017-02-01

    We investigated the efficacy of supplementing the diet with choline or betaine in ameliorating lipid accumulation induced by vitamin B6 (B6) deficiency in rat liver. Male Wistar rats were fed a control, B6-deficient, choline-supplemented (2, 4, or 6 g choline bitartrate/kg diet) B6-deficient diet or betaine-supplemented (1, 2, or 4 g betaine anhydrous/kg diet) B6-deficient diet for 35 d; all diets contained 9 g L-methionine (Met)/kg diet. Choline or betaine supplementation attenuated liver lipid deposition and restored plasma lipid profiles to control levels. These treatments restored the disruptions in Met metabolism and the phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio induced by B6 deficiency in liver microsomes. These results suggest that choline and betaine ameliorated liver lipid accumulation induced by B6 deficiency via recovery of Met metabolism and very low-density lipoprotein secretion by restoring the supply of PC derived from PE.

  15. 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

  16. Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.

    PubMed

    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.

  17. Iodine volatility. [PWR; BWR

    SciTech Connect

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

    1984-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Cecil, Eric; McDaniel, James C.

    2005-05-01

    A planar laser-induced fluorescence (PLIF) technique is discussed and applied to measurement of time-averaged values of velocity and temperature in an I2-seeded N2 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.

  19. 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.

  20. [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.

  1. 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

  2. Assessment of iodine nutrition in populations: past, present, and future.

    PubMed

    Zimmermann, Michael B; Andersson, Maria

    2012-10-01

    Iodine status has been historically assessed by palpation of the thyroid and reported as goiter rates. Goiter is a functional biomarker that can be applied to both individuals and populations, but it is subjective. Iodine status is now assessed using an objective biomarker of exposure, i.e., urinary iodine concentrations (UICs) in spot samples and comparison of the median UIC to UIC cut-offs to categorize population status. This has improved standardization, but inappropriate use of the crude proportion of UICs below the cut-off level of 100 µg/L to estimate the number of iodine-deficient children has led to an overestimation of the prevalence of iodine deficiency. In this review, a new approach is proposed in which UIC data are extrapolated to iodine intakes, adjusted for intraindividual variation, and then interpreted using the estimated average requirement cut-point model. This may allow national programs to define the prevalence of iodine deficiency in the population and to quantify the necessary increase in iodine intakes to ensure sufficiency. In addition, thyroglobulin can be measured on dried blood spots to provide an additional sensitive functional biomarker of iodine status.

  3. Iodine Absorption Cells Purity Testing.

    PubMed

    Hrabina, Jan; Zucco, Massimo; Philippe, Charles; Pham, Tuan Minh; Holá, Miroslava; Acef, Ouali; Lazar, Josef; Číp, Ondřej

    2017-01-06

    This article deals with the evaluation of the chemical purity of iodine-filled absorption cells and the optical frequency references used for the frequency locking of laser standards. We summarize the recent trends and progress in absorption cell technology and we focus on methods for iodine cell purity testing. We compare two independent experimental systems based on the laser-induced fluorescence method, showing an improvement of measurement uncertainty by introducing a compensation system reducing unwanted influences. We show the advantages of this technique, which is relatively simple and does not require extensive hardware equipment. As an alternative to the traditionally used methods we propose an approach of hyperfine transitions' spectral linewidth measurement. The key characteristic of this method is demonstrated on a set of testing iodine cells. The relationship between laser-induced fluorescence and transition linewidth methods will be presented as well as a summary of the advantages and disadvantages of the proposed technique (in comparison with traditional measurement approaches).

  4. [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.

  5. Riboflavin deficiency induces a significant change in proteomic profiles in HepG2 cells

    PubMed Central

    Xin, Zhonghao; Pu, Lingling; Gao, Weina; Wang, Yawen; Wei, Jingyu; Shi, Tala; Yao, Zhanxin; Guo, Changjiang

    2017-01-01

    Riboflavin deficiency is widespread in many regions over the world, especially in underdeveloped countries. In this study, we investigated the effects of riboflavin deficiency on protein expression profiles in HepG2 cells in order to provide molecular information for the abnormalities induced by riboflavin deficiency. HepG2 cells were cultured in media containing different concentrations of riboflavin. Changes of cell viability and apoptosis were assessed. A comparative proteomic analysis was performed using a label-free shotgun method with LC–MS/MS to investigate the global changes of proteomic profiles in response to riboflavin deficiency. Immunoblotting test was used to validate the results of proteomic approach. The cell viability and apoptosis tests showed that riboflavin was vital in maintaining the cytoactivity of HepG2 cells. The label-free proteomic analysis revealed that a total of 37 proteins showing differential expression (±2 fold, p < 0.05) were identified after riboflavin deficiency. Bioinformatics analysis indicated that the riboflavin deficiency caused an up-regulation of Parkinson’s disease pathway, steroid catabolism, endoplasmic reticulum stress and apoptotic process, while the fatty acid metabolism, tricarboxylic citrate cycle, oxidative phosphorylation and iron metabolism were down-regulated. These findings provide a molecular basis for the elucidation of the effects caused by riboflavin deficiency. PMID:28367977

  6. Cystathionine γ-Lyase Deficiency Protects Mice from Galactosamine/Lipopolysaccharide-Induced Acute Liver Failure

    PubMed Central

    Shirozu, Kazuhiro; Tokuda, Kentaro; Marutani, Eizo; Lefer, David; Wang, Rui

    2014-01-01

    Abstract Aims: Acute liver failure (ALF) is a fatal syndrome attributed to massive hepatocyte death. Hydrogen sulfide (H2S) has been reported to exert cytoprotective or cytotoxic effects. Here, we examined the role of cystathionine γ-lyase (CSE, an enzyme produces H2S) in ALF induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). Results: Wild-type (WT) mice exhibited high mortality rate, prominent liver injury, and increased plasma alanine aminotransferase levels after GalN/LPS challenge. Congenital deficiency or chemical inhibition of CSE by DL-propargylglycine attenuated GalN/LPS-induced liver injury. CSE deficiency markedly improved survival rate and attenuated GalN/LPS-induced upregulation of inflammatory cytokines and activation of caspase 3 and poly (ADP-ribose) polymerase (PARP) in the liver. CSE deficiency protected primary hepatocytes from GalN/tumor necrosis factor-α (TNF-α)-induced cell death without affecting LPS-induced TNF-α production from primary peritoneal macrophages. Beneficial effects of CSE deficiency were associated with markedly elevated homocysteine and thiosulfate levels, upregulation of NF-E2 p45-related factor 2 (Nrf2) and antioxidant proteins, activation of Akt-dependent anti-apoptotic signaling, and inhibition of GalN/LPS-induced JNK phosphorylation in the liver. Finally, administration of sodium thiosulfate (STS) attenuated GalN/LPS-induced liver injury via activation of Akt- and Nrf2-dependent signaling and inhibition of GalN/LPS-induced JNK phosphorylation in WT mice. Innovation: These results suggest that inhibition of CSE or administration of STS prevents acute inflammatory liver failure by augmenting thiosulfate levels and upregulating antioxidant and anti-apoptotic defense in the liver. Conclusion: Congenital deficiency or chemical inhibition of CSE increases thiosulfate levels in the liver and prevents ALF at least in part by augmentation of antioxidant and anti-apoptotic mechanisms. Antioxid. Redox Signal. 20, 204

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

    PubMed

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

    2016-04-05

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

  8. Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy

    PubMed Central

    Kannan, Sankaranarayanan; Muthusamy, Vasanthi R.; Whitehead, Kevin J.; Wang, Li; Gomes, Aldrin V.; Litwin, Sheldon E.; Kensler, Thomas W.; Abel, E. Dale; Hoidal, John R.; Rajasekaran, Namakkal S.

    2013-01-01

    Aims Mutant protein aggregation (PA) cardiomyopathy (MPAC) is characterized by reductive stress (RS), PA (of chaperones and cytoskeletal components), and ventricular dysfunction in transgenic mice expressing human mutant CryAB (hmCryAB). Sustained activation of nuclear erythroid-2 like factor-2 (Nrf2) causes RS, which contributes to proteotoxic cardiac disease. The goals of this pre-clinical study were to (i) investigate whether disrupting Nrf2-antioxidant signalling prevents RS and rescues redox homeostasis in hearts expressing the mutant chaperone and (ii) elucidate mechanisms that could delay proteotoxic cardiac disease. Methods and results Non-transgenic (NTG), transgenic (TG) with MPAC and MPAC-TG:Nrf2-deficient (Nrf2-def) mice were used in this study. The effects of Nrf2 diminution (Nrf2±) on RS mediated MPAC in TG mice were assessed at 6–7 and 10 months of age. The diminution of Nrf2 prevented RS and prolonged the survival of TG mice (∼50 weeks) by an additional 20–25 weeks. The TG:Nrf2-def mice did not exhibit cardiac hypertrophy at even 60 weeks, while the MPAC-TG mice developed pathological hypertrophy and heart failure starting at 24–28 weeks of age. Aggregation of cardiac proteins was significantly reduced in TG:Nrf2-def when compared with TG mice at 7 months. Preventing RS and maintaining redox homeostasis in the TG:Nrf2-def mice ameliorated PA, leading to decreased ubiquitination of proteins. Conclusion Nrf2 deficiency rescues redox homeostasis, which reduces aggregation of mutant proteins, thereby delaying the proteotoxic pathological cardiac remodelling caused by RS and toxic protein aggregates. PMID:23761402

  9. 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.

  10. 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

  11. 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

  12. Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase.

    PubMed

    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; Endres, Matthias

    2008-07-09

    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.

  13. 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

  14. Improving iodine nutritional status and increasing prevalence of autoimmune thyroiditis in children

    PubMed Central

    Palaniappan, Srinivasan; Shanmughavelu, Lakshmi; Prasad, Hemchand K.; Subramaniam, Sundari; Krishnamoorthy, Nedunchezian; Lakkappa, Lakshmi

    2017-01-01

    Objective: The objective of this study is to evaluate the link between excess iodine intake as evidenced by increased urinary iodine excretion (UIE) and autoimmune thyroiditis in children and to assess the correlation between UIE and thyroid microsomal antibody (thyroid peroxidase [TPO]) titers in children. Materials and Methods: All children with goiter between age group 6 and 12 years, were subjected to blood tests for free thyroxine, thyroid stimulating hormone, and TPO antibody, fine needle aspiration was advised for all children with goiter. Forty-three children with confirmed autoimmune thyroiditis served as cases, and 43 children with euthyroid goiter with workup negative for autoimmune thyroiditis and iodine deficiency were enrolled as controls. UIE was estimated in spot urine sample for both cases and controls. The levels of urinary iodine were compared between cases and controls. Results: The levels of urinary iodine were significantly higher in children with autoimmune thyroiditis as compared with control. There was a positive correlation between UIE and antimicrosomal antibody titers among cases. Among cases 65% children had subclinical hypothyroidism, 27.9% had overt hypothyroidism and 7% of cases, and 100% of controls had euthyroid functional status. Excessive (≥300 μg/L) UIE was strongly associated with autoimmune thyroiditis. If the UIE level is ≥ 300 μg/L, then there is 17.94 times higher chance of having amiodarone-induced thyrotoxicosis than those who have UIE level < 300 μg/L (P < 0.001). Conclusions: A possible association between increased iodine intake and autoimmune thyroiditis was found in this study. Excessive iodine intake may trigger thyroid autoimmunity and eventually thyroid hypofunction. PMID:28217504

  15. Resolution of adalimumab-induced psoriasis after vitamin D deficiency treatment.

    PubMed

    Werner de Castro, Gláucio Ricardo; Neves, Fabrício Souza; Pereira, Ivanio Alves; Fialho, Sonia Cristina Magalhaes Souza; Ribeiro, Giovana; Zimmermann, Adriana Fontes

    2012-05-01

    Tumoral necrosis factor alpha blockers are very efficient in the treatment of many inflammatory systemic diseases, including rheumatoid arthritis and psoriasis. However, a paradoxical arouse of psoriasiform lesions may occur in a few patients taking anti-TNFα. The etiology of this rare side effect is still a mystery, and its treatment may be difficult. The authors report the resolution of adalimumab-induced psoriasis in a woman with rheumatoid arthritis after the use of high vitamin D(3) doses for the treatment of vitamin D deficiency. This is the first report of resolution of anti-TNFα-induced psoriasiform lesions by high doses of vitamin D(3) in a patient with rheumatoid arthritis and vitamin D deficiency. This case raises interesting questions on the role of vitamin D deficiency in the pathogenesis of this side effect and on the possible usefulness of high-dose vitamin D(3) in its treatment.

  16. 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.

  17. 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.

  18. 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

  19. The Iodine Content in Urine, Faeces and Selected Organs of Rats Fed Lettuce Biofortified with Iodine Through Foliar Application.

    PubMed

    Rakoczy, Roksana; Kopeć, Aneta; Piątkowska, Ewa; Smoleń, Sylwester; Skoczylas, Łukasz; Leszczyńska, Teresa; Sady, Włodzimierz

    2016-12-01

    Iodine is an essential trace element for humans. Foliar application of micronutrients is successfully used in order to increase the concentration of essential elements in vegetables. The aim of this study was to evaluate the iodine absorption in the rat organism fed foliar biofortified lettuce. The presented study was consisted of the vegetative and animal experiment. In the vegetative experiment with lettuce, two combinations of foliar application were used: (1) control-without iodine application and (2) iodine application in the potassium iodide (KI) form. In the animal experiment, Wistar rats were divided to four groups, which received one of four diets: (1) C-control diet containing iodine in the KI form, (2) D-diet deficient in iodine, (3) D + BL-diet containing biofortified lettuce, and (4) D + CL-diet containing control lettuce (as the only source of iodine in diet, respectively). The diets contained 0.260, 0.060, 0.254 and 0.075 mg I/kg, respectively. In order to determine the iodine absorption in the rat organisms, the content of this trace element was measured in urine, faeces and in selected organs with the use of the ICP-OES technique. Foliar application of the KI increased the content of iodine in lettuce. The rats from the D + BL group excreted significantly less iodine in their urine and faeces and also accumulated more iodine in the organs than the rats from the C group. Iodine with biofortified lettuce was much bioavailable for rodents than iodine from control diet. Biofortified lettuce can be a source of iodine in a diet of human and can improve iodine nutrition.

  20. Myeloperoxidase deficiency attenuates nitrogen mustard-induced skin injuries

    PubMed Central

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Orlicky, David J.; White, Carl W.; Agarwal, Rajesh

    2014-01-01

    The pathologic mechanisms of skin injuries, following the acute inflammatory response induced by vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) exposure, are poorly understood. Neutrophils which accumulate at the site of injury, abundantly express myeloperoxidase (MPO), a heme protein that is implicated in oxidant-related antimicrobial and cytotoxic responses. Our previous studies have shown that exposure to SM analog 2-chloroethyl ethyl sulfide (CEES) or NM results in an inflammatory response including increased neutrophilic infiltration and MPO activity. To further define the role of neutrophil-derived MPO in NM-induced skin injury, here we used a genetic approach and examined the effect of NM exposure (12 h and 24 h) on previously established injury endpoints in C57BL/6J wild type (WT) and B6.129X1-MPOtm1Lus/J mice (MPO KO), homozygous null for MPO gene. NM exposure caused a significant increase in skin bi-fold thickness, epidermal thickness, microvesication, DNA damage and apoptosis in WT mice compared to MPO KO mice. MPO KO mice showed relatively insignificant effect. Similarly, NM-induced increases in the expression of inflammatory and proteolytic mediators, including COX-2, iNOS and MMP-9 in WT mice, while having a significantly lower effect in MPO KO mice. Collectively, these results show that MPO, which generates microbicidal oxidants, plays an important role in NM-induced skin injuries. This suggests the development of mechanism-based treatments against NM- and SM-induced skin injuries that inhibit MPO activity and attenuate MPO-derived oxidants. PMID:24631667

  1. Dietary selenium deficiency exacerbates lipopolysaccharide-induced inflammatory response in mouse mastitis models.

    PubMed

    Wei, Zhengkai; Yao, Minjun; Li, Yimeng; He, Xuexiu; Yang, Zhengtao

    2014-12-01

    Selenium (Se) is an essential micronutrient that plays a critical role in anti-inflammatory processes and antioxidant defense system. In this study, we investigated the effects of dietary selenium deficiency on lipopolysaccharide (LPS)-induced mastitis in mouse models. Se content in the liver was assessed by fluorescent atomic absorption spectrometry. Glutathione peroxidase (GPx) activity in the blood, myeloperoxidase (MPO) activity, tumor necrosis actor alpha (TNF-α), and interleukin (IL)-1β in the supernatant of the mammary tissue were determined according to the corresponding kits. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions were evaluated by Western blotting. The results showed that the Se-deficient mouse model was successfully replicated, and selenium deficiency exacerbated mammary gland histopathology, increased the expressions of TNF-α and IL-1β, and facilitated the activation of iNOS and COX-2 in LPS-induced mouse mastitis. In conclusion, our studies demonstrated that selenium deficiency resulted in more severe inflammatory response in LPS-induced mouse mastitis.

  2. Sirtuin-6 deficiency exacerbates diabetes induced impairment of wound healing

    PubMed Central

    Thandavarayan, Rajarajan A; Garikipati, Venkata Naga Srikanth; Joladarashi, Darukeshwara; Babu, Sahana Suresh; Jeyabal, Prince; Verma, Suresh K; Mackie, Alexander R; Khan, Mohsin; Arumugam, Somasundaram; Watanabe, Kenichi; Kishore, Raj; Krishnamurthy, Prasanna

    2015-01-01

    Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However the role of sirtuin 6 (SIRT6), a NAD+-dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyze the role of SIRT6 in cutaneous wound healing, paired 6 mm stented wound were created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and non-sensed siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. SIRT6-siRNA treated diabetic wound showed impaired healing, which was associated with reduced capillary density (CD31 staining vessels) when compared to control treatment. Interestingly, SIRT6 deficiency decreased vascular endothelial growth factor (VEGF) expression and proliferation markers in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes nuclear factor kB (NF-kB) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α and interleukin-1β) and increased oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wound aggravates proinflammatory response by increasing NF-kB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that activation of SIRT6 signaling might be a potential therapeutic approach for promoting wound healing in diabetics. PMID:26010430

  3. Radioactive Iodine Treatment for Hyperthyroidism

    MedlinePlus

    ... Balance › Radioactive Iodine for Hyperthyroidism Fact Sheet Radioactive Iodine for Hyperthyroidism April, 2012 Download PDFs English Zulu ... prepare for RAI or surgery. How does radioactive iodine treatment work? Iodine is important for making thyroid ...

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

    Vigani, Gianpiero

    2012-01-01

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

  6. Dietary Iodine Intake of the Australian Population after Introduction of a Mandatory Iodine Fortification Programme

    PubMed Central

    Charlton, Karen; Probst, Yasmine; Kiene, Gabriella

    2016-01-01

    To address mild iodine deficiency in Australia, a mandatory fortification program of iodised salt in bread was implemented in 2009. This study aimed to determine factors associated with achieving an adequate dietary iodine intake in the Australian population post-fortification, and to assess whether bread consumption patterns affect iodine intake in high-risk groups. Using nationally representative data of repeated 24-h dietary recalls from the 2011–2012 Australian National Nutrition and Physical Activity Survey, dietary iodine intakes and food group contributions were compared by age, socioeconomic status (SES), and geographical remoteness (N = 7735). The association between fortified bread intake and adequacy of iodine intake (meeting age and sex-specific Estimated Average Requirements) was investigated using logistic regression models in women of childbearing age 14–50 years (n = 3496) and children aged 2–18 years (n = 1772). The effect of SES on bread consumption was further investigated in a sub group of children aged 5–9 years (n = 488). Main sources of iodine intake at the time of the survey were cereal and cereal products, followed by milk products and dishes. Differences in iodine intake and dietary iodine habits according to age, SES and location were found (p < 0.001) for women of child-bearing age. Fortified bread consumption at ≥100 g/day was associated with five times greater odds of achieving an adequate iodine intake (OR 5.0, 95% CI 4.96–5.13; p < 0.001) compared to lower bread consumption in women and 12 times in children (OR 12.34, 95% CI 1.71–89.26; p < 0.001). Disparities in dietary iodine intake exist within sectors of the Australian population, even after mandatory fortification of a staple food. On-going monitoring and surveillance of iodine status is required. PMID:27827915

  7. 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

  8. 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.

  9. Increased Sucrose in the Hypocotyls of Radish Sprouts Contributes to Nitrogen Deficiency-Induced Anthocyanin Accumulation

    PubMed Central

    Su, Nana; Wu, Qi; Cui, Jin

    2016-01-01

    Effects of nitrogen (N) deficiency and sucrose (Suc) addition on regulation of anthocyanin biosynthesis and their relationship were investigated in this study. Radish sprouts subjected to N deficiency had 50% higher anthocyanin accumulation than when grown in Hoagland solution (a nutrient medium with all macronutrients). The contents of endogenous soluble sugars (Suc, fructose, and glucose) in the hypocotyls were also markedly increased by N limitation, with Suc showing the highest increase. Inhibition of carbohydrate biosynthesis by addition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) also eliminated N deficiency-induced anthocyanin accumulation. The latter was further supported by the expression of anthocyanin biosynthesis related genes and decreased activities of nitrate reductase in the presence of Suc. Together our results indicate that N deficiency-induced anthocyanin accumulation was, at least partly, dependent on the increase of the soluble sugar, especially Suc. This work is the first comprehensive study on relationship between N deficiency and sugar content on anthocyanin accumulation in the hypocotyls of radish sprouts. PMID:28083009

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

    PubMed

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

    2012-11-01

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

  11. 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.

  12. CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-κB activation

    PubMed Central

    Grabiner, Brian C.; Blonska, Marzenna; Lin, Pei-Chun; You, Yun; Wang, Donghai; Sun, Jiyuan; Darnay, Bryant G.; Dong, Chen; Lin, Xin

    2007-01-01

    G protein-coupled receptors (GPCRs) play pivotal roles in regulating various cellular functions. Although many GPCRs induce NF-κB activation, the molecular mechanism of GPCR-induced NF-κB activation remains largely unknown. CARMA3 (CARD and MAGUK domain-containing protein 3) is a scaffold molecule with unknown biological functions. By generating CARMA3 knockout mice using the gene targeting approach, here we show CARMA3 is required for GPCR-induced NF-κB activation. Mechanistically, we found that CARMA3 deficiency impairs GPCR-induced IκB kinase (IKK) activation, although it does not affect GPCR-induced IKKα/β phosphorylation, indicating that inducible phosphorylation of IKKα/β alone is not sufficient to induce its kinase activity. We also found that CARMA3 is physically associated with NEMO/IKKγ, and induces polyubiquitination of an unknown protein(s) that associates with NEMO, likely by linking NEMO to TRAF6. Consistently, we found TRAF6 deficiency also abrogates GPCR-induced NF-κB activation. Together, our results provide the genetic evidence that CARMA3 is required for GPCR-induced NF-κB activation. PMID:17438001

  13. Adaptive response of the heart to long-term anemia induced by iron deficiency.

    PubMed

    Naito, Yoshiro; Tsujino, Takeshi; Matsumoto, Mika; Sakoda, Tsuyoshi; Ohyanagi, Mitsumasa; Masuyama, Tohru

    2009-03-01

    Anemia is common in patients with chronic heart failure and an independent predictor of poor prognosis. Chronic anemia leads to left ventricular (LV) hypertrophy and heart failure, but its molecular mechanisms remain largely unknown. We investigated the mechanisms, including the molecular signaling pathway, of cardiac remodeling induced by iron deficiency anemia (IDA). Weanling Sprague-Dawley rats were fed an iron-deficient diet for 20 wk to induce IDA, and the molecular mechanisms of cardiac remodeling were evaluated. The iron-deficient diet initially induced severe anemia, which resulted in LV hypertrophy and dilation with preserved systolic function associated with increased serum erythropoietin (Epo) concentration. Cardiac STAT3 phosphorylation and VEGF gene expression increased by 12 wk of IDA, causing angiogenesis in the heart. Thereafter, sustained IDA induced upregulation of cardiac hypoxia inducible factor-1alpha gene expression and maintained upregulation of cardiac VEGF gene expression and cardiac angiogenesis; however, sustained IDA promoted cardiac fibrosis and lung congestion, with decreased serum Epo concentration and cardiac STAT3 phosphorylation after 20 wk of IDA compared with 12 wk. Upregulation of serum Epo concentration and cardiac STAT3 phosphorylation is associated with a beneficial adaptive mechanism of anemia-induced cardiac hypertrophy, and later decreased levels of these molecules may be critical for the transition from adaptive cardiac hypertrophy to cardiac dysfunction in long-term anemia. Understanding the mechanism of cardiac maladaptation to anemia may lead to a new strategy for treatment of chronic heart failure with anemia.

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

    PubMed

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

    2011-07-07

    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.

  15. Marginal biotin deficiency can be induced experimentally in humans using a cost-effective outpatient design.

    PubMed

    Stratton, Shawna L; Henrich, Cindy L; Matthews, Nell I; Bogusiewicz, Anna; Dawson, Amanda M; Horvath, Thomas D; Owen, Suzanne N; Boysen, Gunnar; Moran, Jeffery H; Mock, Donald M

    2012-01-01

    To date, marginal, asymptomatic biotin deficiency has been successfully induced experimentally by the use of labor-intensive inpatient designs requiring rigorous dietary control. We sought to determine if marginal biotin deficiency could be induced in humans in a less expensive outpatient design incorporating a self-selected, mixed general diet. We sought to examine the efficacy of three outpatient study designs: two based on oral avidin dosing and one based on a diet high in undenatured egg white for a period of 28 d. In study design 1, participants (n = 4; 3 women) received avidin in capsules with a biotin binding capacity of 7 times the estimated dietary biotin intake of a typical self-selected diet. In study design 2, participants (n = 2; 2 women) received double the amount of avidin capsules (14 times the estimated dietary biotin intake). In study design 3, participants (n = 5; 3 women) consumed egg-white beverages containing avidin with a biotin binding capacity of 7 times the estimated dietary biotin intake. Established indices of biotin status [lymphocyte propionyl-CoA carboxylase activity; urinary excretion of 3-hydroxyisovaleric acid, 3-hydroxyisovaleryl carnitine (3HIA-carnitine), and biotin; and plasma concentration of 3HIA-carnitine] indicated that study designs 1 and 2 were not effective in inducing marginal biotin deficiency, but study design 3 was as effective as previous inpatient study designs that induced deficiency by egg-white beverage. Marginal biotin deficiency can be induced experimentally by using a cost-effective outpatient design by avidin delivery in egg-white beverages. This design should be useful to the broader nutritional research community.

  16. 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.

  17. Ethanol-induced developmental neurodegeneration in secretin receptor-deficient mice.

    PubMed

    Hwang, Dong-Woo; Givens, Bennet; Nishijima, Ichiko

    2009-05-06

    Alcohol exposure during brain development induces neuronal cell death in the brain. Several neuroactive peptides have been shown to protect against alcohol-induced cell death. Secretin is a peptide hormone, and the secretin receptor is expressed in the gut and the brain. To explore a potential role of secretin signal against ethanol neurotoxicity during brain development, secretin receptor-deficient mice were exposed to ethanol on postnatal day 4. We identified significant ethanol-induced apoptosis in the external granular layer of the secretin receptor-deficient cerebellum and in the striatum after ethanol treatment. During the early postnatal period, there is a proliferation of granular cell progenitors that reside in the external granular layer. The results suggest that secretin signal plays a neuroprotective role of neuronal progenitor cells against the neurotoxicity of ethanol.

  18. Myeloid mineralocorticoid receptor deficiency inhibits aortic constriction-induced cardiac hypertrophy in mice.

    PubMed

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

    2014-01-01

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

  19. 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

  20. FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury.

    PubMed

    Corona, Benjamin T; Rouviere, Clement; Hamilton, Susan L; Ingalls, Christopher P

    2008-08-01

    Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction uncoupling. FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [ryanodine receptor (RyR1)] and plays an important role in excitation-contraction coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (tibialis anterior and extensor digitorum longus muscles) strength in skeletal muscle-specific FKBP12-deficient and wild-type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts. Histological damage of the tibialis anterior muscle was assessed after injury. Body weight and peak isometric and eccentric torques were lower in FKBP12-deficient mice compared with WT mice. There were no differences between FKBP12-deficient and WT mice in preinjury peak isometric and eccentric torques when normalized to body weight, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12-deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice, despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12-deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice.

  1. Mechanism of phytohormone involvement in feedback regulation of cotton leaf senescence induced by potassium deficiency

    PubMed Central

    Tian, Xiaoli

    2012-01-01

    To elucidate the phytohormonal basis of the feedback regulation of leaf senescence induced by potassium (K) deficiency in cotton (Gossypium hirsutum L.), two cultivars contrasting in sensitivity to K deficiency were self- and reciprocally grafted hypocotyl-to-hypocotyl, using standard grafting (one scion grafted onto one rootstock), Y grafting (two scions grafted onto one rootstock), and inverted Y grafting (one scion grafted onto two rootstocks) at the seedling stage. K deficiency (0.03mM for standard and Y grafting, and 0.01mM for inverted Y grafting) increased the root abscisic acid (ABA) concentration by 1.6- to 3.1-fold and xylem ABA delivery rates by 1.8- to 4.6-fold. The K deficiency also decreased the delivery rates of xylem cytokinins [CKs; including the zeatin riboside (ZR) and isopentenyl adenosine (iPA) type] by 29–65% and leaf CK concentration by 16–57%. The leaf ABA concentration and xylem ABA deliveries were consistently greater in CCRI41 (more sensitive to K deficiency) than in SCRC22 (less sensitive to K deficiency) scions under K deficiency, and ZR- and iPA-type levels were consistently lower in the former than in the latter, irrespective of rootstock cultivar or grafting type, indicating that cotton shoot influences the levels of ABA and CKs in leaves and xylem sap. Because the scions had little influence on phytohormone levels in the roots (rootstocks) of all three types of grafts and rootstock xylem sap (collected below the graft union) of Y and inverted Y grafts, it appears that the site for basipetal feedback signal(s) involved in the regulation of xylem phytohormones is the hypocotyl of cotton seedlings. Also, the target of this feedback signal(s) is more likely to be the changes in xylem phytohormones within tissues of the hypocotyl rather than the export of phytohormones from the roots. PMID:22962680

  2. 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.

  3. 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.

  4. An evaluation of the effectiveness of water iodinator system to supply iodine to selected schools in Terengganu, Malaysia.

    PubMed

    Lim, K K; Siti Rohana, D; Zawiah, A; Wan Nazaimoon, W M

    2006-12-01

    This is a cross-sectional study conducted from January to September 2004 in a group of school children aged 8 -10 years old. The schools and study subjects were selected using stratified systematic sampling technique. A total of 44 schools and 1100 subjects were selected from schools with iodinator and schools without iodinator. Samples collected were spot urine and drinking water. Dietary and iodised water consumption data were obtained from interviews. A total of 931 subjects (84.6%) responded; 558 (50.7%) from schools with iodinator and 373 (33.9%) from schools without iodinator. Results showed that in more than half (53.8%) of the schools with iodinators, mean water iodine level was below 25 microg/L. The study population in Terengganu was found to be mildly iodine deficient with an overall median urine iodine concentration (uIC) of 74 microg/L. Based on WHO criteria, 4.1% with uIC <20 microg/L (severe), 19.5% with uIC between 20-49 microg/L (moderate), 49.2% with uIC between 50-99 microg/L (mild) and 27.2% was iodine sufficient with uIC >100 microg/L. Majority of the study subjects were found to have high seafood intake (> 90%) and low in goitrogen food intake. This study suggests water iodinator system may not be a suitable method of supplying iodine and an alternative is needed in order to eradicate the iodine deficiency problem seen in some parts of Malaysia.

  5. Systemic iodine absorption after preoperative antisepsis using povidone-iodine in cataract surgery-- an open controlled study.

    PubMed

    Below, H; Behrens-Baumann, W; Bernhardt, C; Völzke, H; Kramer, A; Rudolph, P

    2006-01-01

    After preoperative conjunctival and periorbital antisepsis with povidone-iodine (PVP-I), the systemic absorption of iodine after cataract surgery was measured to evaluate the risk of thyroid side effects. Five different combinations of PVP-I alone or in combination with PVP-I-free antiseptics were applied to the conjunctiva and periorbital skin. An iodine-free product served as control. Iodide and creatinine in urine were analyzed before intervention and 24 and 48 h postoperatively. Depending on the concentration and application site, 0.3-4.5% of the total applied iodine or 3.6-45.4% of the free iodine were absorbed. The range of urine iodine excretion was between 11.7 and 71.0 mug iodine/g creatinine, depending on the PVP-I concentration and the site of application. The increase in iodine excretion was significant at 24 h postoperatively in trials receiving PVP-I both periorbitally and conjunctivally, depending of the concentration used. Because the iodine absorption is only slight and of doubtful clinical relevance, presurgical conjunctival antisepsis can be achieved with 1.25% PVP-I; so far clinically manifest anamnestic thyroid disorders are excluded. Presently, periorbital skin antisepsis with PVP-I cannot be recommended until data on thyroid metabolism in the population have been collected and evaluated, especially in a region currently or previously deficient in iodine.

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

    PubMed Central

    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.

    2015-01-01

    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

  7. Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

    PubMed

    Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

    2016-11-01

    In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

  8. Effect of excess iodine intake on thyroid on human health.

    PubMed

    Koukkou, Eftychia G; Roupas, Nikolaos D; Markou, Kostas B

    2017-04-01

    The recommended daily intake of iodide, is 150 μg for adolescents and adults, 250 μg for pregnancy and lactation. Thyroid gland is an effective collector of iodine. The active iodine uptake along the basolateral membrane of thyroid cell is followed by its transport to the apical edge of the cell and then to the follicle lumen. TSH acts through cAMP and stimulates NIS gene expression and protein synthesis. The major proportion of iodine in the thyroid gland is bound to Thyroglobulin. The non-organic intrathyroidal iodine is usually low, but significantly greater compared to plasma. Large doses of iodine reduce both the uptake and the organification (Wolff-Chaikoff effect) and cause partial inhibition of Tg proteolysis. The thyroid gland has several protective mechanisms resulting on the maintenance of normal thyroid function despite wide fluctuations of the daily iodine intake. Ingestion of several commonly used drugs and food conservatives results in acute or chronic excessive iodine intake. Failure to escape from the iodine induced organification inhibition can cause hypothyroidism, which is temporary and subsides after iodine exposure ceases. Iodine excess may also establish a status of excessive thyroid hormone synthesis and release, thus inducing autonomic thyroid function in iodopenic areas or can contribute to the development of iodine-induced hyperthyroidism in iodine abundant areas. The anti-arrhythmic Amiodarone, is a benzofuranic product with a very high iodine content, is associated with either hypo- or hyperthyroidism development. In the presence of defective auto-protective mechanisms, excessive iodine ingestion can divert the normal thyroid function.

  9. Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis

    PubMed Central

    Nakahama, Taisuke; Kimura, Akihiro; Nguyen, Nam Trung; Chinen, Ichino; Hanieh, Hamza; Nohara, Keiko; Fujii-Kuriyama, Yoshiaki; Kishimoto, Tadamitsu

    2011-01-01

    The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis have not been elucidated. Here, we show that Ahr deficiency ameliorated collagen-induced arthritis, a mouse model of RA. Collagen-immunized Ahr KO mice showed decreased serum levels of such proinflammatory cytokines as IL-1β and IL-6. The Th17 and Th1 cell populations in lymph nodes from these mice decreased and increased, respectively, whereas the percentage of regulatory T cells was unchanged. Interestingly, a lack of Ahr specifically in T cells significantly suppressed collagen-induced arthritis development, whereas Ahr deficiency in macrophages had no effect. These finding indicate that the development of experimental autoimmune arthritis depends on the presence of Ahr in T cells, and that Th1/Th17 balance may be particularly important for this process. PMID:21825138

  10. [Is iodination of cooking salt still necessary? Current studies on iodine supply in Switzerland].

    PubMed

    Supersaxo, Z; Selz, B; Hasler, P; Wespi, H J; Abelin, T; Bürgi, H

    1991-03-09

    Salt with 3.75 mg iodide per kg was introduced in Switzerland stepwise in the individual cantons between 1922 and 1952. The iodide content was raised to 7.5 mg in 1962 and to 15 mg per kg in 1980. 92% of retail salt and 78% of all salt for human consumption (including salt used in industrial food processing) was iodized in 1989. Under this measure, prevalence of grade 1b or larger goiter dropped continuously to a present value of 1.3% in school-children and 0.3% in male army recruits. Endemic cretinism has disappeared completely. Urinary iodine has reached the desired range of 150 +/- 77 (SD) micrograms per g creatinine. The following facts prove that iodization of salt (and not other changes of food habits) have corrected the iodine deficiency in Switzerland: 1. Urinary iodine is highly correlated with urinary sodium. Backward extrapolation yields a theoretical urinary iodine of 30 micrograms per g creatinine in the absence of iodized salt, a value typical of severe deficiency. 2. Goiter prevalence declined later in those cantons which introduced iodized salt last. 3. Surrounding countries without iodized salt (France, Italy, Federal Republic of Germany, Spain) suffer from considerable iodine deficiency with areas of high goiter prevalence and even endemic cretinism. The new data underscore the absolute and continued need for iodized salt in Switzerland.

  11. 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.

  12. RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury.

    PubMed

    Zhang, Zhuo; Zhou, Jie; Liao, Changli; Li, Xiaobing; Liu, Minghua; Song, Daqiang; Jiang, Xian

    2017-04-01

    Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.

  13. Iodine stability in salt double-fortified with iron and iodine.

    PubMed

    Diosady, L L; Alberti, J O; Ramcharan, K; Mannar, M G Venkatesh

    2002-06-01

    Deficiencies in small quantities of micronutrients, especially iodine and iron, severely affect more than a third of the world's population, resulting in serious public health consequences, especially for women and young children. Salt is an ideal carrier of micronutrients. The double fortification of salt with both iodine and iron is an attractive approach to the reduction of both anemia and iodine-deficiency disorders. Because iodine is unstable under the storage conditions found during the manufacturing, distribution, and sale of salt in most developing countries, the effects of packaging materials and environmental conditions on the stability of salt double-fortified with iron and iodine were investigated. Salt was double-fortified with potassium iodide or potassium iodate and with ferrous sulfate or ferrous fumarate. The effects of stabilizers on the stability of iodine and iron were followed by storing the salt under three conditions that represent the extremes of normal distribution and sale for salt in developing countries: room temperature (25 degrees C) with 50%-70% relative humidity, 40 degrees C with 60% relative humidity, and 40 degrees C with 100% relative humidity. The effects of stabilizers, such as sodium hexametaphosphate (SHMP), calcium carbonate, calcium silicate, and dextrose were investigated. None of the combinations of iron and iodine compounds was stable at elevated temperatures. Essentially all of the iodine was lost over a period of six months. SHMP effectively slowed down the iodine loss, whereas magnesium chloride, a typical hygroscopic impurity, greatly accelerated this process. Calcium carbonate did not have a sparing effect on iodine, despite contrary indications in the literature. Ferrous sulfate-fortified salts generally turned yellow and developed an unpleasant rusty flavor. Salt fortified with ferrous fumarate and potassium, iodide was reasonably stable and maintained its organoleptic properties, making it more likely to be

  14. 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

  15. 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.

  16. 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.

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

    PubMed Central

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

    2016-01-01

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

  18. 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

  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. Geographical distribution of drinking-water with high iodine level and association between high iodine level in drinking-water and goitre: a Chinese national investigation.

    PubMed

    Shen, Hongmei; Liu, Shoujun; Sun, Dianjun; Zhang, Shubin; Su, Xiaohui; Shen, Yanfeng; Han, Hepeng

    2011-07-01

    Excessive iodine intake can cause thyroid function disorders as can be caused by iodine deficiency. There are many people residing in areas with high iodine levels in drinking-water in China. The main aim of the present study was to map the geographical distribution of drinking-water with high iodine level in China and to determine the relationship between high iodine level in drinking-water and goitre prevalence. Iodine in drinking-water was measured in 1978 towns of eleven provinces in China, with a total of 28,857 water samples. We randomly selected children of 8-10 years old, examined the presence of goitre and measured their urinary iodine in 299 towns of nine provinces. Of the 1978 towns studied, 488 had iodine levels between 150 and 300 μg/l in drinking-water, and in 246 towns, the iodine level was >300 μg/l. These towns are mainly distributed along the original Yellow River flood areas, the second largest river in China. Of the 56 751 children examined, goitre prevalence was 6.3 % in the areas with drinking-water iodine levels of 150-300 μg/l and 11.0 % in the areas with drinking-water iodine >300 μg/l. Goitre prevalence increased with water and urinary iodine levels. For children with urinary iodine >1500 μg/l, goitre prevalence was 3.69 times higher than that for those with urinary iodine levels of 100-199 μg/l. The present study suggests that drinking-water with high iodine levels is distributed in eleven provinces of China. Goitre becomes more prevalent with the increase in iodine level in drinking-water. Therefore, it becomes important to prevent goitre through stopping the provision of iodised salt and providing normal drinking-water iodine through pipelines in these areas in China.

  1. Prevalence of maternal dietary iodine insufficiency in the north east of England: implications for the fetus

    PubMed Central

    Kibirige, M; Hutchison, S; Owen, C; Delves, H

    2004-01-01

    Background: Maternal subclinical hypothyroidism is a cause of poor neurodevelopment outcome in the offspring. Although iodine deficiency is the most common cause of hypothyroidism world wide, there are no screening programmes for it in the United Kingdom where the population is assumed to be iodine replete. Objective: To determine the prevalence of reduced iodine intake by measuring urinary iodide concentrations in pregnant and non-pregnant women from the north east of England. Methods: Urinary iodide excretion (UIE) rate was estimated using inductively coupled mass spectrometry in 227 women at 15 weeks gestation and in 227 non-pregnant age matched controls. A reduced intake of iodine is indicated by a concentration in urine of less than 50 µg/l or less than 0.05 µg iodine/mmol creatinine. Results: Eight (3.5%) pregnant women and 13 (5.7%) controls had a reduced iodine/creatinine ratio. These values were higher when UIE was expressed as iodine concentration: 16 (7%) and 20 (8.8%) respectively. Ninety (40%) of the pregnant women had a UIE of 0.05–0.10, which is consistent with borderline deficiency. Conclusion: In this study, 3.5% of pregnant women had evidence of iodine deficiency, and 40% may be borderline deficient. Larger scale studies are required to estimate the true prevalence of iodine deficiency in the United Kingdom. PMID:15321965

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

    PubMed

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

    2007-05-01

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

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

    PubMed

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

    2006-06-01

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

  4. 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

  5. A review of the iodine status of UK pregnant women and its implications for the offspring

    PubMed Central

    Bath, Sarah C.; Rayman, Margaret P.

    2015-01-01

    Iodine, as a component of the thyroid hormones, is crucial for brain development and is therefore especially important during pregnancy when the brain is developing most rapidly. While randomised controlled trials of pregnant women in regions of severe iodine deficiency have shown that prenatal iodine deficiency causes impaired cognition, less is known of the effects in regions of mild deficiency. This is relevant to the UK as the World Health Organisation now classifies the UK as mildly iodine deficient, based on a national study of 14-15 year old schoolgirls in 2011. We have previously published a study, using samples and data from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC) that found an association between low iodine status in early pregnancy (urinary iodine-to-creatinine ratio < 150 μg/g) and lower verbal IQ and reading scores in the offspring. Though the women in ALSPAC were recruited in the early 1990s, the results of the study are still relevant as their iodine status was similar to that reported in recent studies of UK pregnant women. This review discusses the evidence that mild-to-moderate iodine deficiency during pregnancy has deleterious effects on child neurodevelopment and relates that evidence to the data on iodine status in the UK. It has highlighted a need for nationwide data on iodine status of pregnant women and that a randomised controlled trial of iodine supplementation in pregnant women in a region of mild-to-moderate iodine deficiency with child outcomes as the primary endpoint is required. PMID:25663363

  6. 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.

  7. Iodine and Selenium Intakes of Postmenopausal Women in New Zealand.

    PubMed

    Brough, Louise; Gunn, Caroline A; Weber, Janet L; Coad, Jane; Jin, Ying; Thomson, Jasmine S; Mauze, Mathilde; Kruger, Marlena C

    2017-03-09

    Iodine and selenium are required for thyroid function. This study investigated iodine and selenium intakes in healthy, women aged 50-70 years (n = 97) from three cities in the North Island of New Zealand, after mandatory fortification of bread with iodised salt. Iodine and selenium concentrations were determined in 24-h urine samples; daily intakes were extrapolated from amounts in urine (90% and 55% of daily intake, respectively). Three day diet diaries (3DDD) also estimated selenium and iodine (excluding iodised salt) intake. Median urinary iodine concentration (UIC) was 57 (41, 78) µg/L, indicating mild iodine deficiency. Estimated median iodine intake based on urine was 138 (100, 172) µg/day, below Recommended Dietary Intake (RDI) (150 µg/day) with 25% below Estimated Average Requirement (EAR) (100 µg/day). Estimated median selenium intake was 50 (36, 71) µg/day based on urine and 45 (36, 68) µg/day using 3DDD, below RDI (60 µg/day) with 49%-55% below EAR (50 µg/day). Median bread intakes were low at 1.8 (1.1, 2.7) serves/day; 25% consumed ≤1 serve/day. Although population iodine intakes improved following mandatory fortification, some had low intakes. Selenium intakes remain low. Further research should investigate thyroid function of low consumers of iodine fortified bread and/or selenium in New Zealand.

  8. Iodine and Selenium Intakes of Postmenopausal Women in New Zealand

    PubMed Central

    Brough, Louise; Gunn, Caroline A.; Weber, Janet L.; Coad, Jane; Jin, Ying; Thomson, Jasmine S.; Mauze, Mathilde; Kruger, Marlena C.

    2017-01-01

    Iodine and selenium are required for thyroid function. This study investigated iodine and selenium intakes in healthy, women aged 50–70 years (n = 97) from three cities in the North Island of New Zealand, after mandatory fortification of bread with iodised salt. Iodine and selenium concentrations were determined in 24-h urine samples; daily intakes were extrapolated from amounts in urine (90% and 55% of daily intake, respectively). Three day diet diaries (3DDD) also estimated selenium and iodine (excluding iodised salt) intake. Median urinary iodine concentration (UIC) was 57 (41, 78) µg/L, indicating mild iodine deficiency. Estimated median iodine intake based on urine was 138 (100, 172) µg/day, below Recommended Dietary Intake (RDI) (150 µg/day) with 25% below Estimated Average Requirement (EAR) (100 µg/day). Estimated median selenium intake was 50 (36, 71) µg/day based on urine and 45 (36, 68) µg/day using 3DDD, below RDI (60 µg/day) with 49%–55% below EAR (50 µg/day). Median bread intakes were low at 1.8 (1.1, 2.7) serves/day; 25% consumed ≤1 serve/day. Although population iodine intakes improved following mandatory fortification, some had low intakes. Selenium intakes remain low. Further research should investigate thyroid function of low consumers of iodine fortified bread and/or selenium in New Zealand. PMID:28282932

  9. 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.

  10. RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation

    PubMed Central

    Jones, Robert A.; Robinson, Tyler J.; Liu, Jeff C.; Shrestha, Mariusz; Voisin, Veronique; Ju, YoungJun; Chung, Philip E.D.; Pellecchia, Giovanna; Fell, Victoria L.; Bae, SooIn; Muthuswamy, Lakshmi; Egan, Sean E.; Jiang, Zhe; Leone, Gustavo; Bader, Gary D.; Schimmer, Aaron

    2016-01-01

    Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low–like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration–approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC. PMID:27571409

  11. The Effects of Iodine Fortified Milk on the Iodine Status of Lactating Mothers and Infants in an Area with a Successful Salt Iodization Program: A Randomized Controlled Trial

    PubMed Central

    Nazeri, Pantea; Mirmiran, Parvin; Tahmasebinejad, Zhale; Hedayati, Mehdi; Delshad, Hossein; Azizi, Fereidoun

    2017-01-01

    Iodine deficiency during the first two years of life may cause irreversible brain damage and mental retardation. The aim of the present study was to investigate, for the first time, the effect of iodine fortified milk on the iodine status of lactating mothers and their infants. In this multicenter randomized controlled trial, 84 lactating mother-infant pairs from health care centers were randomly selected. After meeting the inclusion criteria, lactating mothers were randomly assigned to two groups: the iodine fortified milk group and the control group (n = 42 each). Maternal and infant urine and breast milk samples were collected at 3–5 (baseline), 7, 10, 14 days, and 1 month postpartum, for a measurement of the iodine concentration. A total of 84 lactating mothers, with a mean age of 28.2 ± 4.5 years, and 84 infants, with a mean age of 4.2 ± 0.7 days, were included in the study. Compared to mothers of the control group, mothers receiving iodine fortified milk had higher urinary (p < 0.001) and breast milk (p < 0.001) iodine concentrations. Urinary iodine levels in infants revealed no significant differences between the two groups. The findings of this study indicate that supplementation with daily iodine fortified milk provides iodine nutrition adequacy among lactating mothers. However, it had no effect on the iodine status of infants, who were previously iodine sufficient. PMID:28241419

  12. 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

  13. Akt activation prevents the force drop induced by eccentric contractions in dystrophin-deficient skeletal muscle.

    PubMed

    Blaauw, Bert; Mammucari, Cristina; Toniolo, Luana; Agatea, Lisa; Abraham, Reimar; Sandri, Marco; Reggiani, Carlo; Schiaffino, Stefano

    2008-12-01

    Skeletal muscles of the mdx mouse, a model of Duchenne Muscular Dystrophy, show an excessive reduction in the maximal tetanic force following eccentric contractions. This specific sign of the susceptibility of dystrophin-deficient muscles to mechanical stress can be used as a quantitative test to measure the efficacy of therapeutic interventions. Using inducible transgenesis in mice, we show that when Akt activity is increased the force drop induced by eccentric contractions in mdx mice becomes similar to that of wild-type mice. This effect is not correlated with muscle hypertrophy and is not blocked by rapamycin treatment. The force drop induced by eccentric contractions is similar in skinned muscle fibers from mdx and Akt-mdx mice when stretch is applied directly to skinned fibers. However, skinned fibers isolated from mdx muscles exposed to eccentric contractions in vivo develop less isometric force than wild-type fibers and this force depression is completely prevented by Akt activation. These experiments indicate that the myofibrillar-cytoskeletal system of dystrophin-deficient muscle is highly susceptible to a damage caused by eccentric contraction when elongation is applied in vivo, and this damage can be prevented by Akt activation. Microarray and PCR analyses indicate that Akt activation induces up-regulation of genes coding for proteins associated with Z-disks and costameres, and for proteins with anti-oxidant or chaperone function. The protein levels of utrophin and dysferlin are also increased by Akt activation.

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

    PubMed

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

    2015-05-01

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

  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. 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.

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

    PubMed

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

    2013-01-01

    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 cross-links (DPCs). Repair of DPCs may be mediated by the Fanconi anemia pathway; however, data supporting the involvement of this pathway are 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 h, 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.

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

    PubMed

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

    2016-05-01

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

  19. Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway.

    PubMed

    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.

  20. 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

  1. Intercellular adhesion molecule-1 (ICAM-1) deficiency protects mice against severe forms of experimentally induced colitis

    PubMed Central

    Bendjelloul, F; Malý, P; Mandys, V; Jirkovská, M; Prokešová, L; Tučková, L; Tlaskalová-Hogenová, H

    2000-01-01

    ICAM-1 (CD54), the ligand for LFA-1 and Mac-1, is up-regulated during inflammatory reaction on the activated vascular endothelium. To determine its role in intestinal inflammation, we induced acute experimental colitis in mice with a deleted ICAM-1 gene, by feeding them with 3% dextran sodium sulphate (DSS) in drinking water for 7 days. Chronic colitis was elicited by DSS similarly, followed by 2 weeks with water. In the acute phase of inflammation, ICAM-1-deficient mice exhibited a significantly lower mortality rate (5%) than control C57Bl/6J mice (35%). Control animals, but not the ICAM-1-deficient mice, exhibited diarrhoea and rectal bleeding. Histological examination of large-bowel samples evaluated the intensity of inflammatory changes, and type and extent of mucosal lesions. In the acute phase, 33.3% of samples from ICAM-1-deficient mice exhibited mucosal defects (flat and fissural ulcers), predominantly mild to moderate inflammatory infiltrate within the lamina propria mucosae and lower grades of mucosal lesions. Much stronger inflammatory changes were present in control animals, flat ulcers (sometimes multiple) and fissural ulcers being observed in 62.5% of samples. Mucosal inflammatory infiltrate was moderate to severe, typically with higher grades of mucosal lesions. In chronic colitis, smaller inflammatory changes were found in the large bowel. The two mouse strains differed, the chronic colitis being accompanied by an increased serum level of anti-epithelial IgA autoantibodies in C57Bl/6 control mice but not in ICAM-1-deficient mice. These findings provide direct evidence of the participation of ICAM-1 molecule in the development of experimentally induced intestinal inflammation. PMID:10606964

  2. 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

  3. Complement component C5 deficiency reduces edema formation in murine ligation-induced acute pancreatitis.

    PubMed

    Merriam, L T; Webster, C; Joehl, R J

    1997-01-01

    The complement cascade is activated in humans and animals with acute pancreatitis. Activation of complement component C5 liberates C5a, C5a-desarg, and terminal complement complexes (TCCs) that increase capillary permeability, edema, and leukocyte chemotaxis at injured sites. Complement activation plays a major role in pathogenesis of capillary leak and edema formation in severe acute pancreatitis; however, the contribution of C5 (C5a/C5a-desarg, TCCs) has not been defined. Using He gene mutant mice lacking circulating C5, the role of C5 in ligation-induced acute pancreatitis was evaluated. We performed the following experiments: C5-sufficient (Hc1/Hc1) and C5-deficient (Hc0/Hc0) mice had bile and pancreatic ducts ligated. Sham-operated mice had ducts dissected but not ligated. Mice were killed at 4, 8, and 24 hr after bilepancreatic duct ligation. Serologic and morphologic evidences of acute pancreatitis were evaluated. Pancreatic edema was assessed using analysis of pancreatic water content, histologic edema score, and determination of wet weight ratio. After 4, 8, and 24 hr of bile-pancreatic duct ligation, hyperamylasemia and histologic changes of acute pancreatitis were observed in both C5-deficient and C5-sufficient mice. Edema developed in all mice with acute pancreatitis. However, when compared to C5-sufficient mice, mice deficient in C5 developed significantly less pancreatic edema at both 8 and 24 hr of bile-pancreatic duct ligation. This difference was not observed 4 hr after induction of acute pancreatitis. We conclude that C5 contributes to edema formation in murine ligation-induced acute pancreatitis. The presence of an early C5-independent phase, in conjunction with the observation of significant edema in mice deficient in C5, suggests there are other mediators of edema formation in this acute pancreatitis model.

  4. [Dietary iodine provision of the population in the Krasnoyarsk Territory].

    PubMed

    Shevchenko, I Iu

    2008-01-01

    The paper analyzes the time course of changes in the intake of staple foods in the Krasnoyarsk Territory in 1998-2005. It is shown that the ingestion of iodine-rich foods has not increased greatly and it is low and does not provide the population with this essential micronutrient. The actual content of iodine in the study samples of food and its raw material is several times less than the tabulated values. The contribution of the staple foods to the provision of the Krasnoyarsk Territory's population with iodine is assessed. The total level of dietary iodine deficiency is estimated. Iodine-fortified salt and foods should be widely used under special conditions providing the transportation and storage of biologically value foods, during which there are inevitable losses of the trace element occur.

  5. 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

  6. 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

  7. Excessive iodine intake during pregnancy in Somali refugees.

    PubMed

    Kassim, Ismail A R; Ruth, Laird J; Creeke, Paul I; Gnat, Danielle; Abdalla, Fathia; Seal, Andrew J

    2012-01-01

    Iodine deficiency and excess are both associated with adverse health consequences, with fetuses, children and pregnant women being most vulnerable to the devastating effects of severe deficiency. It is often assumed that the iodine status of a population if displaced or in a remote or emergency situation is low. However, there is little evidence available to support this assumption, especially among long-term food-aid-dependent pregnant women. An effectiveness trial of a prenatal multiple-micronutrient supplement that contained 150 µg day(-1) iodine was conducted in two refugee camps in the North Eastern Province of Kenya in 2002. Urinary iodine concentration (UIC) was measured in a subsample of pregnant women attending antenatal care in Dagahaley (control camp) (n = 74) and Ifo (intervention camp) (n = 63). There was no significant difference in median UIC between the two camps (P = 0.118). The combined median UIC was 730 µg L(-1) (interquartile range, 780) (5.77 µmol L(-1)) and exceeded the upper safe limit of 500 µg L(-1) (3.95 µmol L(-1)) for pregnant women (P < 0.001), indicating excessive iodine intake. About 20% of the study subjects had 'more than adequate' urinary iodine, while over 71% had excessive UIC. Salt iodine content varied between 5.1 and 80.1 ppm in the five market salt samples analysed. In conclusion, excessive iodine intake was evident in the Dadaab refugee camps. Further research needs to be conducted to investigate the source of excess iodine, to determine the measures needed to address excessive iodine intake and to reconsider the World Health Organization/World Food Programme/United Nations Children's Fund guidance on supplementation of vulnerable groups in emergencies.

  8. 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

  9. 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

  10. 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.

  11. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    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.

  13. 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

  14. CCR2 deficiency prevents neuronal dysfunction and cognitive impairments induced by cranial irradiation.

    PubMed

    Belarbi, Karim; Jopson, Timothy; Arellano, Carla; Fike, John R; Rosi, Susanna

    2013-02-01

    Cranial irradiation can lead to long-lasting cognitive impairments in patients receiving radiotherapy for the treatment of malignant brain tumors. Recent studies have suggested inflammation as a major contributor to these deficits; we determined if the chemokine (C-C motif) receptor 2 (CCR2) was a mediator of cognitive impairments induced by irradiation. Two-month-old male Ccr2 knockout (-/-) and wild-type mice received 10 Gy cranial irradiation or sham-treatment. One month after irradiation, bromodeoxyuridine was injected intraperitoneally for seven consecutive days to label newly generated cells. At two months postirradiation, cognitive function was assessed by novel object recognition and Morris water maze. Our results show that CCR2 deficiency prevented hippocampus-dependent spatial learning and memory impairments induced by cranial irradiation. Hippocampal gene expression analysis showed that irradiation induced CCR2 ligands such as CCL8 and CCR2 deficiency reduced this induction. Irradiation reduced the number of adult-born neurons in both wild-type and Ccr2(-/-) mice, but the distribution pattern of the adult-born neurons through the granule cell layer was only altered in wild-type mice. Importantly, CCR2 deficiency normalized the fraction of pyramidal neurons expressing the plasticity-related immediate early gene Arc. These data offer new insight into the mechanism(s) of radiation-injury and suggest that CCR2 is a critical mediator of hippocampal neuronal dysfunction and hippocampal cognitive impairments after irradiation. Targeting CCR2 signaling could conceivably provide an effective approach to reduce or prevent the incidence and severity of this serious side effect of ionizing irradiation.

  15. CCR2 deficiency prevents neuronal dysfunction and cognitive impairments induced by cranial irradiation

    PubMed Central

    Belarbi, Karim; Jopson, Timothy; Arellano, Carla; Fike, John R.; Rosi, Susanna

    2013-01-01

    Cranial irradiation can lead to long-lasting cognitive impairments in patients receiving radiotherapy for the treatment of malignant brain tumors. Recent studies have suggested inflammation as a major contributor to these deficits; we determined if the chemokine receptor 2 (CCR2) was a mediator of cognitive impairments induced by irradiation. Two-month-old male Ccr2 knockout (−/−) and wild-type (WT) mice received 10 Gy cranial irradiation or sham-treatment. One month after irradiation, bromodeoxyuridine was injected intraperitoneally for seven consecutive days to label newly generated cells. At two months post-irradiation, cognitive function was assessed by novel object recognition and Morris water maze. Our results demonstrate that CCR2 deficiency prevented hippocampus-dependent spatial learning and memory impairments induced by cranial irradiation. Hippocampal gene expression analysis showed that irradiation induced CCR2 ligands such as CCL8, and CCR2 deficiency reduced this induction. Irradiation reduced the number of adult-born neurons in both WT and Ccr2−/− mice, but the distribution pattern of the adult-born neurons through the granule cell layer was only altered in WT mice. Importantly, CCR2 deficiency normalized the fraction of pyramidal neurons expressing the plasticity-related immediate early gene Arc. These data offer new insight into the mechanism(s) of radiation-injury and suggest that CCR2 is a critical mediator hippocampal neuronal dysfunction and hippocampal cognitive impairments after irradiation. Targeting CCR2 signaling could conceivably provide an effective approach to reduce or prevent the incidence and severity of this serious side effect of ionizing irradiation. PMID:23243025

  16. Genetic deficiency of Syk protects mice from autoantibody-induced arthritis

    PubMed Central

    Jakus, Zoltán; Simon, Edina; Balázs, Bálint; Mócsai, Attila

    2010-01-01

    Objective The Syk tyrosine kinase plays an important role in diverse functions in hematopoietic lineage cells. Although previous in vitro and pharmacologic analyses suggested Syk to be a possible player in the development of autoimmune arthritis, no in vivo genetic studies addressing that issue have yet been reported. The aim of the present study was to test whether genetic deficiency of Syk affects autoantibody-induced experimental arthritis in the K/BxN serum–transfer model. Methods Syk−/− bone marrow chimeras carrying a Syk-deficient hematopoietic system were generated by transplanting Syk−/− fetal liver cells into lethally irradiated wild-type recipients. After complete repopulation of the hematopoietic compartment, autoantibody-mediated arthritis was induced by injection of arthritogenic K/BxN serum. Arthritis development was monitored by macroscopic and microscopic observation of the ankle joints, micro–computed tomography of bone morphology, as well as a joint function assay. Results Genetic deficiency of Syk in the hematopoietic compartment completely blocked the development of all macroscopic and microscopic signs of arthritis. The Syk−/− mutation also prevented the appearance of periarticular bone erosions. Finally, Syk−/− bone marrow chimeras were completely protected from arthritis-induced loss of articular function. Conclusion Our results indicate that Syk is critically involved in the development of all clinically relevant aspects of autoantibody-mediated K/BxN serum–transfer arthritis in experimental mice. These results provide the first in vivo genetic evidence of the role of Syk in the development of autoimmune arthritis. PMID:20201079

  17. Abolishment of TNBS-induced visceral hypersensitivity in mast cell deficient rats.

    PubMed

    Ohashi, Katsuyo; Sato, Yasushi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2008-02-13

    Mucosal mast cells are implicated in visceral hypersensitivity associated with irritable bowel syndrome (IBS). In this study, we investigated the role of mast cells in the development of visceral hypersensitivity by using mast cell deficient (Ws/Ws) rats and their control (W+/W+). In W+/W+ rats, an injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon produced a significant decrease in pain threshold of the distal colon. Severe mucosal necrosis and inflammatory cell infiltration with concomitant increase in tissue myeloperoxidase activity were observed in the proximal colon that was directly insulted by TNBS, whereas neither necrosis nor increased myeloperoxidase activity occurred in the distal colon, indicating that TNBS-induced hypersensitivity is not caused by the local tissue damage or inflammation in the region of the gut where distention stimuli were applied. On the other hand, TNBS failed to elicit visceral hypersensitivity in Ws/Ws rats. This finding indicates that mast cells are essential for development of TNBS-induced visceral hypersensitivity in rats. Since the severity of TNBS-induced proximal colon injury and MPO activity was not affected by mast cell deficiency, it is unlikely that abolishment of visceral hypersensitivity in mast cell deficient rats was a result of altered development of the primary injury in the proximal colon. There was no difference between sham-operated Ws/Ws and W+/W+ rats in colonic pain threshold to distention stimuli, indicating that mast cells play no modulatory roles in normal colonic nociception. The present results support the view that mucosal mast cells play key roles in the pathogenesis of IBS.

  18. MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

    PubMed Central

    Van Hove, Inge; Lefevere, Evy; De Groef, Lies; Sergeys, Jurgen; Salinas-Navarro, Manuel; Libert, Claude; Vandenbroucke, Roosmarijn; Moons, Lieve

    2016-01-01

    Matrix metalloproteinase-3 (MMP-3) is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE) and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU) model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1), interleukin 6 (Il6), cytokine-inducible nitrogen oxide synthase (Nos2) and tumor necrosis factor α (Tnfα), which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP)-1 and (C-X-C motif) ligand 1 (CXCL1). These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation. PMID:27809288

  19. Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice.

    PubMed

    Ruan, Jhen-Wei; Statt, Sarah; Huang, Chih-Ting; Tsai, Yi-Ting; Kuo, Cheng-Chin; Chan, Hong-Lin; Liao, Yu-Chieh; Tan, Tse-Hua; Kao, Cheng-Yuan

    2016-11-28

    The gut microbiota plays profound roles in host metabolism and the inflammatory response associated with the development of obesity. Dusp6-deficient mice have been shown to be resistant to diet-induced obesity, but the mechanism behind this remains unclear. 16S ribosomal RNA gene analysis demonstrated that dusp6-deficient mice harbour unique gut microbiota with resistance to diet-induced-obesity-mediated alteration of the gut microbiome. Using a germ-free mouse model, we found that faecal/gut microbiota derived from dusp6-deficient mice significantly increased energy expenditure and reduced weight gain in recipient wild-type mice fed on a high-fat diet. On analysis of the intestinal transcriptome of dusp6-deficient mice, we found that dusp6 deficiency mainly induced biological processes involved in metabolism and the extracellular matrix, particularly the peroxisome proliferator-activated receptor gamma (Pparγ) pathway and tight-junction genes. Furthermore, dusp6-deficient mice have a high-fat-diet-specific transcriptomic response to reverse the expression of genes associated with intestinal barrier functions and mucosal immunity involved in microbiome homeostasis. This study demonstrates that dusp6 deficiency is a strong genetic factor shaping gut microbiota, and that it confers obesity protection by ameliorating the gut microbiota response to diet-mediated stress.

  20. 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

  1. ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes.

    PubMed

    Liu, Na; Stoica, George; Yan, Mingshan; Scofield, Virginia L; Qiang, Wenan; Lynn, William S; Wong, Paul K Y

    2005-12-01

    ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATM-deficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm(-/-) astrocytes, like Atm(-/-) lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATM-deficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.

  2. Iodine Absorption Cells Purity Testing

    PubMed Central

    Hrabina, Jan; Zucco, Massimo; Philippe, Charles; Pham, Tuan Minh; Holá, Miroslava; Acef, Ouali; Lazar, Josef; Číp, Ondřej

    2017-01-01

    This article deals with the evaluation of the chemical purity of iodine-filled absorption cells and the optical frequency references used for the frequency locking of laser standards. We summarize the recent trends and progress in absorption cell technology and we focus on methods for iodine cell purity testing. We compare two independent experimental systems based on the laser-induced fluorescence method, showing an improvement of measurement uncertainty by introducing a compensation system reducing unwanted influences. We show the advantages of this technique, which is relatively simple and does not require extensive hardware equipment. As an alternative to the traditionally used methods we propose an approach of hyperfine transitions’ spectral linewidth measurement. The key characteristic of this method is demonstrated on a set of testing iodine cells. The relationship between laser-induced fluorescence and transition linewidth methods will be presented as well as a summary of the advantages and disadvantages of the proposed technique (in comparison with traditional measurement approaches). PMID:28067834

  3. 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.

  4. 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.

  5. Ischemia/reperfusion-induced Kidney Injury in Heterozygous PACAP-deficient Mice.

    PubMed

    Laszlo, E; Varga, A; Kovacs, K; Jancso, G; Kiss, P; Tamas, A; Szakaly, P; Fulop, B; Reglodi, D

    2015-09-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with very diverse distribution and functions. Among others, PACAP is a potent cytoprotective peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This also has been shown in different kidney pathologies, including ischemia/reperfusion-induced kidney injury. Similar protective effects of the endogenous PACAP are confirmed by the increased vulnerability of PACAP-deficient mice to different harmful stimuli. Kidneys of homozygous PACAP-deficient mice have more severe damages in renal ischemia/reperfusion and kidney cell cultures isolated from these mice show increased sensitivity to renal oxidative stress. In our present study we raised the question of whether the partial lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient mice also display more severe damage after renal ischemia/reperfusion. Mice underwent 45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation of the kidneys was performed and individual histopathological parameters were graded. Furthermore, we investigated apoptotic markers, cytokine expression, and the activity of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion. We found no difference between the intact kidneys of wild-type and heterozygous mice, but marked differences could be observed following ischemia/reperfusion. Heterozygous PACAP-deficient mice had more severe histological alterations, with significantly higher histopathological scores for most of the tested parameters. Higher level of the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower activity of the antioxidant SOD could be found in these mice. In conclusion, the partial lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion, confirming that PACAP functions as an endogenous protective factor in the kidney.

  6. 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.

  7. 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

  8. FOXO1 Mediates Vitamin D Deficiency-Induced Insulin Resistance in Skeletal Muscle.

    PubMed

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

    2016-03-01

    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. Although 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.

  9. N-Nitrosocarbaryl-induced mutagenesis in Haemophilus influenzae strains deficient in repair and recombination.

    PubMed

    Beattie, K L

    1975-02-01

    Mutagenesis was studied in repair- and recombination-deficient strains of Haemophilus influenzae after treatment with N-nitrosocarbaryl (NC). Three different strains of H. influenzae carrying mutations affecting excision-repair of UV-induced pyrimidine dimers exhibited normal repair of premutational lesions (as detected by decreased mutation yield resulting from post-treatment DNA synthesis delay) and normal nonreplicative mutation fixation. This indicated that neither of these phenomena are caused by the smae repair mechanism that removes UV-induced pyrimidine dimers from the DNA. The recombination-deficient mutant recI is apparently deficient in the replication-dependent mode of NC-induced mutation fixation. This conclusion is based on the following results: (I) NC-induced mutagenesis is lower in the recI strain than in rec+ cells. (2) Repair of premutational lesions (which depends on the existence of replication-dependent mutation fixation for its detection) was not detected in the recI strain. (3) When nonreplicative mutation fixation and final mutation frequency were measured in the same experiment, about I/4 to I/3 of the final mutation yield could be accounted for by nonreplicative mutation fixation in the rec+ strain, whereas all of the mutation could be accounted for in the recI strain by the nonreplicative mutation fixation. (4) When mutation fixation in strain dna9 recI was followed at the permissive (36 degrees) and nonpermissive (41 degrees) temperatures, it became apparent that in the recI strain replication-dependent mutation fixation occurs at early times, but these newly fixed mutations are unstable and disappear at later times, leaving only the mutations fixed by the nonreplicative process. The recI strain exhibits normal repair of NC-induced single-strand breaks or alkali-labile bonds in the DNA labeled before treatment, but is slow in joining discontinuties present in DNA synthesized after treatment. The results are consistent with the idea that

  10. Median Urinary Iodine Concentrations Are Indicative of Adequate Iodine Status among Women of Reproductive Age in Prey Veng, Cambodia.

    PubMed

    Karakochuk, Crystal D; Michaux, Kristina D; Chai, Tze L; Chan, Benny B; Whitfield, Kyly C; Barr, Susan I; McLean, Judy; Talukder, Aminuzzaman; Hou, Kroeun; Ly, Sokhoing; Green, Tim J

    2016-03-03

    Iodine deficiency disorders are estimated to affect over 1.9 million people worldwide. Iodine deficiency is especially serious for women during pregnancy and lactation because of the negative consequences for both mother and infant. The aim of this cross-sectional study was to determine the median urinary iodine concentration (UIC) as a population-level indicator of iodine status among rural women farmers of reproductive age (18-45 years) in the province of Prey Veng, Cambodia. A total of 450 women provided a spot morning urine sample in 2012. Of those women, 93% (n = 420) were non-pregnant and 7% (n = 30) were pregnant at the time of collection. UIC was quantified using the Sandell-Kolthoff reaction with modifications. The median UIC of non-pregnant (139 μg/L) and pregnant women (157 μg/L) were indicative of adequate iodine status using the WHO/UNICEF/ICCIDD epidemiological criteria for both groups (median UIC between 100-199 and 150-249 μg/L, respectively). We conclude that non-pregnant and pregnant women in rural Prey Veng, Cambodia had adequate iodine status based on single spot morning urine samples collected in 2012. More research is warranted to investigate iodine status among larger and more representative populations of women in Cambodia, especially in light of recent policy changes to the national program for universal salt iodization.

  11. 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

  12. ANA deficiency enhances bone morphogenetic protein-induced ectopic bone formation via transcriptional events.

    PubMed

    Miyai, Kentaro; Yoneda, Mitsuhiro; Hasegawa, Urara; Toita, Sayaka; Izu, Yayoi; Hemmi, Hiroaki; Hayata, Tadayoshi; Ezura, Yoichi; Mizutani, Shuki; Miyazono, Kohei; Akiyoshi, Kazunari; Yamamoto, Tadashi; Noda, Masaki

    2009-04-17

    Ectopic bone formation after joint replacement or brain injury in humans is a serious complication that causes immobility of joints and severe pain. However, mechanisms underlying such ectopic bone formation are not fully understood. Bone morphogenetic protein (BMPs) are defined as inducers of ectopic bone formation, and they are regulated by several types of inhibitors. ANA is an antiproliferative molecule that belongs to Tob/BTG family, but its activity in bone metabolism has not been known. Here, we examined the role of ANA on ectopic bone formation activity of BMP. In ANA-deficient and wild-type mice, BMP2 was implanted to induce ectopic bone formation in muscle. ANA deficiency increased mass of newly formed bone in vivo compared with wild-type based on 3D-muCT analyses. ANA mRNA was expressed in bone in vivo as well as in osteoblastic cells in vitro. Such ANA mRNA levels were increased by BMP2 treatment in MC3T3-E1 osteoblastic cells. Overexpression of ANA suppressed BMP-induced expression of luciferase reporter gene linked to BMP response elements in these cells. Conversely, ANA mRNA knockdown by small interference RNA enhanced the BMP-dependent BMP response element reporter expression. It also enhanced BMP-induced osteoblastic differentiation in muscle-derived C2C12 cells. Immunoprecipitation assay indicated that ANA interacts with Smad8. Thus, ANA is a suppressor of ectopic bone formation induced by BMP, and this inhibitory ANA activity is a part of the negative feedback regulation of BMP function.

  13. ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12) Interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) Linking Iron Deficiency and Oxidative Stress Responses.

    PubMed

    Le, Cham Thi Tuyet; Brumbarova, Tzvetina; Ivanov, Rumen; Stoof, Claudia; Weber, Eva; Mohrbacher, Julia; Fink-Straube, Claudia; Bauer, Petra

    2016-01-01

    Plants grown under iron (Fe)-deficient conditions induce a set of genes that enhance the efficiency of Fe uptake by the roots. In Arabidopsis (Arabidopsis thaliana), the central regulator of this response is the basic helix-loop-helix transcription factor FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT). FIT activity is regulated by protein-protein interactions, which also serve to integrate external signals that stimulate and possibly inhibit Fe uptake. In the search of signaling components regulating FIT function, we identified ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12), an abiotic stress-induced transcription factor. ZAT12 interacted with FIT, dependent on the presence of the ethylene-responsive element-binding factor-associated amphiphilic repression motif. ZAT12 protein was found expressed in the root early differentiation zone, where its abundance was modulated in a root layer-specific manner. In the absence of ZAT12, FIT expression was upregulated, suggesting a negative effect of ZAT12 on Fe uptake. Consistently, zat12 loss-of-function mutants had higher Fe content than the wild type at sufficient Fe. We found that under Fe deficiency, hydrogen peroxide (H2O2) levels were enhanced in a FIT-dependent manner. FIT protein, in turn, was stabilized by H2O2 but only in the presence of ZAT12, showing that H2O2 serves as a signal for Fe deficiency responses. We propose that oxidative stress-induced ZAT12 functions as a negative regulator of Fe acquisition. A model where H2O2 mediates the negative regulation of plant responses to prolonged stress might be applicable to a variety of stress conditions.

  14. 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.

  15. Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue.

    PubMed

    Sato, So; Miyake, Masao; Hazama, Akihiro; Omori, Koichi

    2014-07-01

    Although povidone-iodine (PVP-I) has been used as a gargle since 1956, its effectiveness and material safety have been remained controversial. The aim of this study was to investigate the toxicity of PVP-I to epithelial cells in a concentration range significantly lower than that used clinically. Study design was in vitro laboratory investigations and in vivo histological and immunologic analysis. We examined the effects of PVP-I at concentrations of 1 × 10(-2) to 1 × 10(3) μM and 1 × 10(-4) to 1 × 10 μM on HeLa cells as a model of epithelial cells and rat oral mucosa, respectively, after 1 or 2 days of exposure. Annexin V/FLUOS was used to distinguish live, apoptotic and necrotic cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was also used to observe whether apoptotic epithelial cells exist in rat oral mucosa after 1 day of exposure of PVP-I. HeLa cells developed concentration-dependent cytotoxicity, and epithelium of rat oral mucosa was thinned in a concentration-dependent manner. HeLa cell apoptosis increased after 1 × 10(0) μM of PVP-I exposure for 2 days. In the TUNEL method, many apoptotic epithelial cells were observed in the rat oral mucosa after 1 day of exposure to diluted 1 × 10(-2) μM of PVP-I, but minimal apoptotic epithelial cells were observed using 1 × 10(-3) μM of PVP-I. Our findings suggest that exposure to PVP-I, of which concentrations are even lower than those used clinically, causes toxicity in epithelial cells. This knowledge would help us better understand the risk of the use of PVP-I against mucosa.

  16. Iodine generator for reclaimed water purification

    NASA Technical Reports Server (NTRS)

    Wynveen, R. A.; Powell, J. D.; Schubert, F. H. (Inventor)

    1977-01-01

    The system disclosed is for controlling the iodine level in a water supply in a spacecraft. It includes an iodine accumulator which stores crystalline iodine, an electrochemical valve to control the input of iodine to the drinking water and an iodine dispenser. A pump dispenses fluid through the iodine dispenser and an iodine sensor to a potable water tank storage. The iodine sensor electronically detects the iodine level in the water, and through electronic means, produces a correction current control. The correction current control operates the electro-chemical iodine valve to release iodine from the iodine accumulator into the iodine dispenser.

  17. 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.

  18. Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency

    PubMed Central

    Spassieva, Stefka D.; Ji, Xiaojie; Liu, Ye; Gable, Kenneth; Bielawski, Jacek; Dunn, Teresa M.; Bieberich, Erhard; Zhao, Lihong

    2016-01-01

    Sphingolipids exhibit extreme functional and chemical diversity that is in part determined by their hydrophobic moiety, ceramide. In mammals, the fatty acyl chain length variation of ceramides is determined by six (dihydro)ceramide synthase (CerS) isoforms. Previously, we and others showed that mutations in the major neuron-specific CerS1, which synthesizes 18-carbon fatty acyl (C18) ceramide, cause elevation of long-chain base (LCB) substrates and decrease in C18 ceramide and derivatives in the brain, leading to neurodegeneration in mice and myoclonus epilepsy with dementia in humans. Whether LCB elevation or C18 ceramide reduction leads to neurodegeneration is unclear. Here, we ectopically expressed CerS2, a nonneuronal CerS producing C22–C24 ceramides, in neurons of Cers1-deficient mice. Surprisingly, the Cers1 mutant pathology was almost completely suppressed. Because CerS2 cannot replenish C18 ceramide, the rescue is likely a result of LCB reduction. Consistent with this hypothesis, we found that only LCBs, the substrates common for all of the CerS isoforms, but not ceramides and complex sphingolipids, were restored to the wild-type levels in the Cers2-rescued Cers1 mutant mouse brains. Furthermore, LCBs induced neurite fragmentation in cultured neurons at concentrations corresponding to the elevated levels in the CerS1-deficient brain. The strong association of LCB levels with neuronal survival both in vivo and in vitro suggests high-level accumulation of LCBs is a possible underlying cause of the CerS1 deficiency-induced neuronal death. PMID:27162368

  19. Beta-aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency.

    PubMed

    Begriche, Karima; Massart, Julie; Abbey-Toby, Adjé; Igoudjil, Anissa; Lettéron, Philippe; Fromenty, Bernard

    2008-09-01

    Beta-Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild-type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high-calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma beta-hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase-1 was augmented in liver and white adipose tissue. Acetyl-CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin-dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet-induced obesity and related metabolic disorders in low leptin secretors.

  20. Diet-Induced Obesity and Reduced Skin Cancer Susceptibility in Matrix Metalloproteinase 19-Deficient Mice

    PubMed Central

    Pendás, Alberto M.; Folgueras, Alicia R.; Llano, Elena; Caterina, John; Frerard, Françoise; Rodríguez, Francisco; Astudillo, Aurora; Noël, Agnès; Birkedal-Hansen, Henning; López-Otín, Carlos

    2004-01-01

    Matrix metalloproteinase 19 (MMP-19) is a member of the MMP family of endopeptidases that, in contrast to most MMPs, is widely expressed in human tissues under normal quiescent conditions. MMP-19 has been found to be associated with ovulation and angiogenic processes and is deregulated in diverse pathological conditions such as rheumatoid arthritis and cancer. To gain further insights into the in vivo functions of this protease, we have generated mutant mice deficient in Mmp19. These mice are viable and fertile and do not display any obvious abnormalities. However, Mmp19-null mice develop a diet-induced obesity due to adipocyte hypertrophy and exhibit decreased susceptibility to skin tumors induced by chemical carcinogens. Based on these results, we suggest that this enzyme plays an in vivo role in some of the tissue remodeling events associated with adipogenesis, as well as in pathological processes such as tumor progression. PMID:15169894

  1. Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations.

    PubMed

    Bisaz, Reto; Sandi, Carmen

    2012-03-01

    Previous studies in rodents showed that chronic stress induces structural and functional alterations in several brain regions, including shrinkage of the hippocampus and the prefrontal cortex, which are accompanied by cognitive and emotional disturbances. Reduced expression of the neural cell adhesion molecule (NCAM) following chronic stress has been proposed to be crucially involved in neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and altered expression of alternatively spliced NCAM isoforms have been associated with bipolar depression and schizophrenia in humans, we hypothesized that reduced expression of NCAM renders individuals more vulnerable to the deleterious effects of stress on behavior. Here, we specifically questioned whether mice in which the NCAM gene is inactivated in the forebrain by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient mice), display increased vulnerability to stress. We assessed the evolving of depressive-like behaviors and spatial learning and memory impairments following a subchronic stress protocol (2 weeks) that does not result in behavioral dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no behavioral alterations were detected in wild-type littermates after subchronic stress, conditional NCAM-deficient mice showed increased immobility in the tail suspension test and deficits in reversal spatial learning in the water maze. These findings indicate that diminished NCAM expression might be a critical vulnerability factor for the development of behavioral alterations by stress and further support a functional involvement of NCAM in stress-induced cognitive and emotional disturbances.

  2. 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.

  3. 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

  4. Gibberellin deficiency pleiotropically induces culm bending in sorghum: an insight into sorghum semi-dwarf breeding

    PubMed Central

    Ordonio, Reynante L.; Ito, Yusuke; Hatakeyama, Asako; Ohmae-Shinohara, Kozue; Kasuga, Shigemitsu; Tokunaga, Tsuyoshi; Mizuno, Hiroshi; Kitano, Hidemi; Matsuoka, Makoto; Sazuka, Takashi

    2014-01-01

    Regulation of symmetrical cell growth in the culm is important for proper culm development. So far, the involvement of gibberellin (GA) in this process has not yet been demonstrated in sorghum. Here, we show that GA deficiency resulting from any loss-of-function mutation in four genes (SbCPS1, SbKS1, SbKO1, SbKAO1) involved in the early steps of GA biosynthesis, not only results in severe dwarfism but also in abnormal culm bending. Histological analysis of the bent culm revealed that the intrinsic bending was due to an uneven cell proliferation between the lower and upper sides of culm internodes. GA treatment alleviated the bending and dwarfism in mutants, whereas the GA biosynthesis inhibitor, uniconazole, induced such phenotypes in wild-type plants— both in a concentration-dependent manner, indicating an important role of GA in controlling erectness of the sorghum culm. Finally, we propose that because of the tight relationship between GA deficiency-induced dwarfism and culm bending in sorghum, GA-related mutations have unlikely been selected in the history of sorghum breeding, as could be inferred from previous QTL and association studies on sorghum plant height that did not pinpoint GA-related genes. PMID:24924234

  5. NLRP3 Deficiency Improves Angiotensin II-Induced Hypertension But Not Fetal Growth Restriction During Pregnancy.

    PubMed

    Shirasuna, Koumei; Karasawa, Tadayoshi; Usui, Fumitake; Kobayashi, Motoi; Komada, Tadanori; Kimura, Hiroaki; Kawashima, Akira; Ohkuchi, Akihide; Taniguchi, Shun'ichiro; Takahashi, Masafumi

    2015-11-01

    Preeclampsia is a pregnancy-specific syndrome characterized by elevated blood pressure, proteinuria, and intrauterine growth restriction (IUGR). Although sterile inflammation appears to be involved, its pathogenesis remains unclear. Recent evidence indicates that sterile inflammation is mediated through the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes, composed of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1. Here we investigated the role of the NLRP3 inflammasomes in the pathogenesis of preeclampsia using Nlrp3(-/-) and Asc(-/-) (Nlrp3 and Asc deficient) pregnant mice. During pregnancy in mice, continuous infusion of high-dose angiotensin II (AngII) induced hypertension, proteinuria, and IUGR, whereas infusion of low-dose AngII caused hypertension alone. AngII-induced hypertension was prevented in Nlrp3(-/-) mice but not in Asc(-/-), indicating that NLRP3 contributes to gestational hypertension independently of ASC-mediated inflammasomes. Although NLRP3 deficiency had no effect on IUGR, it restored the IL-6 up-regulation in the placenta and kidney of AngII-infused mice. Furthermore, treatment with hydralazine prevented the development of gestational hypertension but not IUGR or IL-6 expression in the placenta and kidney. These findings demonstrate that NLRP3 contributes to the development of gestational hypertension independently of the inflammasomes and that IUGR and kidney injury can occur independent of blood pressure elevation during pregnancy.

  6. 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.

  7. 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.

  8. Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level

    PubMed Central

    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

    2016-01-01

    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

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

    PubMed

    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.

  10. Laser induced fluorescence studies of iodine oxide chemistry. Part II. The reactions of IO with CH3O2, CF3O2 and O3.

    PubMed

    Dillon, Terry J; Tucceri, María E; Crowley, John N

    2006-11-28

    The technique of pulsed laser photolysis was coupled to laser induced fluorescence detection of iodine oxide (IO) to measure rate coefficients, k for the reactions IO + CH(3)O(2)--> products (R1, 30-318 Torr N(2)), IO + CF(3)O(2)--> products (R2, 70-80 Torr N(2)), and IO + O(3)--> OIO + O(2) (R3a). Values of k(1) = (2 +/- 1) x 10(-12) cm(3) molecule(-1) s(-1), k(2) = (3.6 +/- 0.8) x 10(-11) cm(3) molecule(-1) s(-1), and k(3a) <5 x 10(-16) cm(3) molecule(-1) s(-1) were obtained at T = 298 K. In the course of this work, the product yield of IO from the reaction of CH(3)O(2) with I was determined to be close to zero, whereas CH(3)OOI was formed efficiently at 70 Torr N(2). Similarly, no evidence was found for IO formation in the CF(3)O(2) + I reaction. An estimate of the rate coefficients k(CH(3)O(2) + I) = 2 x 10(-11) cm(3) molecule(-1) s(-1) and k(CH(3)OOI + I) = 1.5 x 10(-10) cm(3) molecule(-1) s(-1) was also obtained. The results on k(1)-k(3) are compared to the limited number of previous investigations and the implications for the chemistry of the marine boundary layer are briefly discussed.

  11. Iodine status of Eeyou Istchee community members of northern Quebec, Canada, and potential sources.

    PubMed

    Tam, Benita; Tsuji, Leonard J S; Martin, Ian D; Liberda, Eric N; Ayotte, Pierre; Coté, Suzanne; Dewailly, Éric; Nieboer, Evert

    2015-04-01

    A multi community environment-and-health study among six of the nine communities of Eeyou Istchee in northern Quebec, Canada provided greater insight into iodine intake levels among these Cree First Nation communities. Using data from this large population-based study, descriptive statistics of measured urinary iodine concentrations (UICs) and iodine-creatinine ratios (stratified by age, sex, community of residence, and water consumption) were calculated, and the associations between independent variables and iodine concentration measures were examined through a general linear model. Traditional food consumption contributions were examined through Pearson partial correlation tests and linear regression analyses; and the importance of water sources through ANOVA. Generally speaking, urinary iodine levels of Eeyou Istchee community members were within the adequate range set out by the World Health Organization, though sex and community differences existed. However, men in one community were considered to be at risk of iodine deficiency. Older participants had significantly higher mean iodine-creatinine ratios than younger participants (15-39 years = 90.50 μmol mol(-1); >39 years = 124.52 μmol mol(-1)), and consumption of beaver (Castor canadensis) meat, melted snow and ice, and bottled water were predictive of higher iodine excretion. It is concluded that using both urinary iodine indicators can be helpful in identifying subgroups at greater risk of iodine deficiency.

  12. 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

  13. 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.

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

    PubMed

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

    2016-02-01

    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 (Gch1(fl/fl)Tie2cre mice) received a 24hour 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 Gch1(fl/fl)Tie2cre 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 Gch1(fl/fl)Tie2cre mesenteric arteries. Ex vivo LPS treatment decreased vasoconstriction response to phenylephrine in aortic rings from wild-type and not in Gch1(fl/fl)Tie2cre 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.

  15. Hypothyroidism Among Military Infants Born in Countries of Varied Iodine Nutrition Status

    DTIC Science & Technology

    2010-02-01

    Naval Health Research Center Hypothyroidism among Military Infants Born in Countries of Varied Iodine Nutrition Status . M. M. Cranston...Naval Health Research Center 140 Sylvester Road San Diego, California 92106 RESEARCH ARTICLE Open Access Hypothyroidism among military infants born...deficiencies in iodine intake on children and pregnant women has been questioned. This study was designed to compare hypothyroidism among infants

  16. Role of Hydrogen Sulfide on Autophagy in Liver Injuries Induced by Selenium Deficiency in Chickens.

    PubMed

    Wenzhong, Wang; Tong, Zhang; Hongjin, Lin; Ying, Chang; Jun, Xing

    2017-01-01

    Selenium (Se) is an indispensable trace mineral that was associated with liver injuries in animal models. Hydrogen sulfide (H2S) is involved in many liver diseases, and autophagy can maintain liver homeostasis with a stress stimulation. However, little is known about the correlation between H2S and autophagy in the liver injury chicken models induced by Se deficiency. In this study, we aimed to investigate the correlation between H2S and autophagy in the liver injury chicken models. We randomly divided 120 1-day-old chickens into two equal groups. The control group was fed with complete food with a Se content of 0.15 mg/kg, and the Se-deficiency group (lab group) was fed with a Se-deficient diet with a Se content of 0.033 mg/kg. When the time comes to 15, 25, and 35 days, the chickens were sacrificed (20 each). The liver tissues were gathered and examined for pathological observations, the mRNA and protein levels of H2S synthases (CSE, CBS, and 3-MST) and the mRNA and protein levels of autophagy-related genes. The results showed that the expression of CSE, CBS, and 3-MST and H2S production were higher in the lab group than in the control group. Swellings, fractures, and vacuolizations were visible in the mitochondria cristae in the livers of the lab group and autophagosomes were found as well. In addition, the expression of autophagy-related genes (ATG5, LC3-I, LC3-II, Beclin1, and Dynein) was higher in the lab group than in the control group (p < 0.05) while TOR decreased significantly in the lab group (p < 0.05). The results showed that H2S and autophagy were involved in the liver injury chicken models, and H2S was correlated with autophagy.

  17. 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.

  18. Triplex structures induce DNA double strand breaks via replication fork collapse in NER deficient cells

    PubMed Central

    Kaushik Tiwari, Meetu; Adaku, Nneoma; Peart, Natoya; Rogers, Faye A.

    2016-01-01

    Structural alterations in DNA can serve as natural impediments to replication fork stability and progression, resulting in DNA damage and genomic instability. Naturally occurring polypurine mirror repeat sequences in the human genome can create endogenous triplex structures evoking a robust DNA damage response. Failures to recognize or adequately process these genomic lesions can result in loss of genomic integrity. Nucleotide excision repair (NER) proteins have been found to play a prominent role in the recognition and repair of triplex structures. We demonstrate using triplex-forming oligonucleotides that chromosomal triplexes perturb DNA replication fork progression, eventually resulting in fork collapse and the induction of double strand breaks (DSBs). We find that cells deficient in the NER damage recognition proteins, XPA and XPC, accumulate more DSBs in response to chromosomal triplex formation than NER-proficient cells. Furthermore, we demonstrate that XPC-deficient cells are particularly prone to replication-associated DSBs in the presence of triplexes. In the absence of XPA or XPC, deleterious consequences of triplex-induced genomic instability may be averted by activating apoptosis via dual phosphorylation of the H2AX protein. Our results reveal that damage recognition by XPC and XPA is critical to maintaining replication fork integrity and preventing replication fork collapse in the presence of triplex structures. PMID:27298253

  19. Inflammation and increased IDO in hippocampus contribute to depression-like behavior induced by estrogen deficiency.

    PubMed

    Xu, Yongjun; Sheng, Hui; Tang, Zhiping; Lu, Jianqiang; Ni, Xin

    2015-07-15

    Estrogen deficiency is involved in the development of depression. However, the mechanism underlying estrogen modulates depression-like behavior remains largely unknown. Inflammation and indoleamine-2,3-dioxygenase (IDO) have been shown to play pivotal roles in various depression models. The objective of the present study was to investigate whether estrogen deficiency-induced depression-like behavior is associated with inflammation and IDO activation in brain. The results showed that ovariectomy resulted in depression-like behavior in female rats and caused a decrease in 5-HT content and an increase in levels of IDO, IFN-γ, IL-6, toll like receptor (TLR)-4 and phosphorylated NF-κB (p65 subunit) in hippocampus but not in prefrontal cortex (PFC). 17β-Estradiol (E2) treatment ameliorated depression-like behavior and restored above neurochemical alternations in hippocampus in ovariectomized rats. Partial correlation analysis showed that the levels of phosphorylated p65, IFN-γ and IL-6 in hippocampus correlated to serum E2 level. Our study suggests that estrogen inhibits inflammation and activates of IDO and maintains 5-HT level in hippocampus, thereby ameliorating depression-like behavior.

  20. 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.

  1. 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

  2. Gpr177 deficiency impairs mammary development and prohibits Wnt-induced tumorigenesis.

    PubMed

    Maruyama, Eri Ohfuchi; Yu, H-M Ivy; Jiang, Ming; Fu, Jiang; Hsu, Wei

    2013-01-01

    Aberrant regulation of the Wnt pathway, essential for various developmental processes, is tightly linked to human breast cancers. By hijacking this evolutionary conserved signaling pathway, cancer cells acquire sustaining proliferation ability, leading to modification of physiologic properties necessary for tumor initiation and progression. An enormous wealth of knowledge on the importance of Wnt signaling in breast development and cancer has been obtained, but the cell types responsible for production of this proliferative signal operating within normal and malignant tissues remains poorly understood. Here we report that Wnt production mediated by Gpr177 is essential for mammary morphogenesis. The loss of Gpr177 interferes with mammary stem cells, leading to deficiencies in cell proliferation and differentiation. Genetic analysis further demonstrates an indispensable role of Gpr177 in Wnt-induced tumorigenesis. The Gpr177-deficiency mice are resistant to malignant transformation. This study not only demonstrates the necessity of Wnt in mammary organogenesis but also provides a proof-of-principle for targeting of Gpr177 as a potential new treatment for human diseases with aberrant Wnt stimulation.

  3. Characterization of the Xanthophyll Cycle and Other Photosynthetic Pigment Changes Induced by Iron Deficiency in Sugar Beet (Beta vulgaris L.).

    PubMed

    Morales, F; Abadía, A; Abadía, J

    1990-10-01

    In this work we characterize the changes induced by iron deficiency in the pigment composition of sugar beet (Beta vulgaris L.) leaves. When sugar beet plants were grown hydroponically under limited iron supply, neoxanthin and beta-carotene decreased concomitantly with chlorophyll a, whereas lutein and the carotenoids within the xanthophyll cycle were less affected. Iron deficiency caused major increases in the lutein/chlorophyll a and xanthophyll cycle pigments/chlorophyll a molar ratios. Xanthophyll cycle carotenoids in Fe-deficient plants underwent epoxidations and de-epoxidations in response to ambient light conditions. In dark adapted Fe-deficient plants most of the xanthophyll cycle pigment pool was in the epoxidated form violaxanthin. We show, both by HPLC and by in vivo 505 nanometers absorbance changes, that in Fe deficient plants and in response to light, the de-epoxidated forms antheraxanthin and zeaxanthin were rapidly formed at the expense of violaxanthin. Several hours after returning to dark, the xanthophyll cycle was shifted again toward violaxanthin. The ratio of variable to maximum chlorophyll fluorescence from intact leaves was decreased by iron deficiency. However, in iron deficient leaves this ratio was little affected by light conditions which displace the xanthophyll cycle toward epoxidation or de-epoxidation. This suggests that the functioning of the xanthophyll cycle is not necessarily linked to protection against excess light input.

  4. 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.

  5. Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis

    PubMed Central

    Ryz, Natasha R.; Lochner, Arion; Bhullar, Kirandeep; Ma, Caixia; Huang, Tina; Bhinder, Ganive; Bosman, Else; Wu, Xiujuan; Innis, Sheila M.; Jacobson, Kevan

    2015-01-01

    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

  6. Radioactive iodine uptake

    MedlinePlus

    ... too much thyroid hormone medicine or supplements) Iodine overload Subacute thyroiditis (swelling or inflammation of the thyroid ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  7. Iodine Clock Reaction.

    ERIC Educational Resources Information Center

    Mitchell, Richard S.

    1996-01-01

    Describes a combination of solutions that can be used in the study of kinetics using the iodine clock reaction. The combination slows down degradation of the prepared solutions and can be used successfully for several weeks. (JRH)

  8. Adult Lysophosphatidic Acid Receptor 1-Deficient Rats with Hyperoxia-Induced Neonatal Chronic Lung Disease Are Protected against Lipopolysaccharide-Induced Acute Lung Injury

    PubMed Central

    Chen, Xueyu; Walther, Frans J.; Laghmani, El H.; Hoogeboom, Annemarie M.; Hogen-Esch, Anne C. B.; van Ark, Ingrid; Folkerts, Gert; Wagenaar, Gerry T. M.

    2017-01-01

    Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air. After 7 weeks, male rats received either LPS (2 mg kg−1) or 0.9% NaCl by intraperitoneal injection. Alveolar development and lung inflammation were investigated by morphometric analysis, IL-6 production, and mRNA expression of cytokines, chemokines, coagulation factors, and an indicator of oxidative stress. Results: LPAR1-deficient and control rats developed hyperoxia-induced neonatal emphysema, which persisted into adulthood, as demonstrated by alveolar enlargement and decreased vessel density. LPAR1-deficiency protected against LPS-induced lung injury. Adult controls with BPD exhibited an exacerbated response toward LPS with an increased expression of pro-inflammatory mRNAs, whereas LPAR1-deficient rats with BPD were less sensitive to this “second hit” with a decreased pulmonary influx of macrophages and neutrophils, interleukin-6 (IL-6) production, and mRNA expression of IL-6, monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant 1, plasminogen activator inhibitor-1, and tissue factor. Conclusion: LPAR1-deficient rats have increased hyperoxia-induced BPD survival rates and, despite the presence of neonatal emphysema, are less sensitive to an aggravated “second hit” than Wistar controls with BPD. Intervening in LPA-LPAR1-dependent signaling may not only have therapeutic potential for neonatal chronic

  9. TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species.

    PubMed

    Yan, Jidong; Xu, Jing; Fei, Yao; Jiang, Congshan; Zhu, Wenhua; Han, Yan; Lu, Shemin

    2016-05-15

    Thioredoxin reductase 2 (TrxR2) is a selenium (Se) containing protein. Se deficiency is associated with an endemic osteoarthropathy characterized by impaired cartilage formation. It is unclear whether TrxR2 have roles in cartilage function. We examined the effects of TrxR2 on chondrogenic ATDC5 cells through shRNA-mediated gene silencing of TrxR2. We demonstrated TrxR2 deficiencies could enhance chondrogenic differentiation and apoptosis of ATDC5 cells. TrxR2 deficiencies increased accumulation of cartilage glycosaminoglycans (GAGs) and mineralization. TrxR2 deficiencies also stimulated expression of extracellular (ECM) gene including Collagen II and Aggrecan. The enhanced chondrogenic properties were further confirmed by activation of Akt signaling which are required for chondrogenesis. In addition, TrxR2 deficiencies promoted chondrocyte proliferation through acceleration of cell cycle progression by increase in both S and G2/M phase cell distribution accompanied with induction of parathyroid hormone-related protein (PTHrP). Moreover, TrxR2 deficiencies induced chondrocyte death via apoptosis and increased cell sensitivity to exogenous oxidative stress. Furthermore, TrxR2 deficiencies induced emission of mitochondrial reactive oxygen species (ROS) without alteration of mitochondrial membrane potential and intracellular ATP content. Finally, treatment of TrxR2 deficiency cells with N-acetylcysteine (NAC) inhibited mitochondrial ROS production and chondrocyte apoptosis. NAC also prevented chondrogenic differentiation of TrxR2 deficiency cells by suppression of ECM gene expression, GAGs accumulation and mineralization, as well as attenuation of Akt signaling. Thus, TrxR2-mediated mitochondrial integrity is indispensable for chondrogenic differentiation of ATDC5 cells. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Se deficiency. Notably, this study also uncover the roles of

  10. Iodine Hall Thruster

    NASA Technical Reports Server (NTRS)

    Szabo, James

    2015-01-01

    Iodine enables dramatic mass and cost savings for lunar and Mars cargo missions, including Earth escape and near-Earth space maneuvers. The demonstrated throttling ability of iodine is important for a singular thruster that might be called upon to propel a spacecraft from Earth to Mars or Venus. The ability to throttle efficiently is even more important for missions beyond Mars. In the Phase I project, Busek Company, Inc., tested an existing Hall thruster, the BHT-8000, on iodine propellant. The thruster was fed by a high-flow iodine feed system and supported by an existing Busek hollow cathode flowing xenon gas. The Phase I propellant feed system was evolved from a previously demonstrated laboratory feed system. Throttling of the thruster between 2 and 11 kW at 200 to 600 V was demonstrated. Testing showed that the efficiency of iodine fueled BHT-8000 is the same as with xenon, with iodine delivering a slightly higher thrust-to-power (T/P) ratio. In Phase II, a complete iodine-fueled system was developed, including the thruster, hollow cathode, and iodine propellant feed system. The nominal power of the Phase II system is 8 kW; however, it can be deeply throttled as well as clustered to much higher power levels. The technology also can be scaled to greater than 100 kW per thruster to support megawatt-class missions. The target thruster efficiency for the full-scale system is 65 percent at high specific impulse (Isp) (approximately 3,000 s) and 60 percent at high thrust (Isp approximately 2,000 s).

  11. 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.

  12. Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling

    PubMed Central

    Wang, Xiao-Dong; Chen, Yuncai; Wolf, Miriam; Wagner, Klaus V.; Liebl, Claudia; Scharf, Sebastian H.; Harbich, Daniela; Mayer, Bianca; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Müller, Marianne B.; Schmidt, Mathias V.

    2011-01-01

    Chronic stress evokes profound structural and molecular changes in the hippocampus, which may underlie spatial memory deficits. Corticotropin-releasing hormone (CRH) and CRH receptor 1 (CRHR1) mediate some of the rapid effects of stress on dendritic spine morphology and modulate learning and memory, thus providing a potential molecular basis for impaired synaptic plasticity and spatial memory by repeated stress exposure. Using adult male mice with CRHR1 conditionally inactivated in the forebrain regions, we investigated the role of CRH-CRHR1 signaling in the effects of chronic social defeat stress on spatial memory, the dendritic morphology of hippocampal CA3 pyramidal neurons, and the hippocampal expression of nectin-3, a synaptic cell adhesion molecule important in synaptic remodeling. In chronically stressed wild-type mice, spatial memory was disrupted, and the complexity of apical dendrites of CA3 neurons reduced. In contrast, stressed mice with forebrain CRHR1 deficiency exhibited normal dendritic morphology of CA3 neurons and mild impairments in spatial memory. Additionally, we showed that the expression of nectin-3 in the CA3 area was regulated by chronic stress in a CRHR1-dependent fashion and associated with spatial memory and dendritic complexity. Moreover, forebrain CRHR1 deficiency prevented the down-regulation of hippocampal glucocorticoid receptor expression by chronic stress but induced increased body weight gain during persistent stress exposure. These findings underscore the important role of forebrain CRH-CRHR1 signaling in modulating chronic stress-induced cognitive, structural and molecular adaptations, with implications for stress-related psychiatric disorders. PMID:21296667

  13. Selenoprotein W redox-regulated Ca2+ channels correlate with selenium deficiency-induced muscles Ca2+ leak

    PubMed Central

    Zhao, Xia; Zhao, Wenchao; Liu, Wei; Yang, Jie; Sattar, Hamid; Zhao, Jinxin; Zhang, Ziwei; Xu, Shiwen

    2016-01-01

    Selenium (Se) deficiency induces Ca2+ leak and calcification in mammal skeletal muscles; however, the exact mechanism is still unclear. In the present study, both Se-deficient chicken muscle models and selenoprotein W (SelW) gene knockdown myoblast and embryo models were used to study the mechanism. The results showed that Se deficiency-induced typical muscular injuries accompanied with Ca2+ leak and oxidative stress (P < 0.05) injured the ultrastructure of the sarcoplasmic reticulum (SR) and mitochondria; decreased the levels of the Ca2+ channels, SERCA, SLC8A, CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 (P < 0.05); and increased the levels of Ca2+ channel PMCA (P < 0.05). Similarly, SelW knockdown also induced Ca2+ leak from the SR and cytoplasm; increased mitochondrial Ca2+ levels and oxidative stress; injured SR and mitochondrial ultrastructure; decreased levels of SLC8A, CACNA1S, ORA1, TRPC1, and TRPC3; and caused abnormal activities of Ca2+ channels in response to inhibitors in myoblasts and chicken embryos. Thus, both Se deficiency and SelW knockdown induced Ca2+ leak, oxidative stress, and Ca2+ channel reduction. In addition, Ca2+ levels and the expression of the Ca2+ channels, RyR1, SERCA, CACNA1S, TRPC1, and TRPC3 were recovered to normal levels by N-acetyl-L-cysteine (NAC) treatment compared with SelW knockdown cells. Thus, with regard to the decreased Ca2+ channels, SelW knockdown closely correlated Se deficiency with Ca2+ leak in muscles. The redox regulation role of SelW is crucial in Se deficiency-induced Ca2+ leak in muscles. PMID:27557522

  14. Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency

    PubMed Central

    Wu, Yalei; Torchia, James; Yao, Wei; Lane, Nancy E.; Lanier, Lewis L.; Nakamura, Mary C.; Humphrey, Mary Beth

    2007-01-01

    Immunoreceptor tyrosine-based activation motif (ITAM) signaling mediated by DAP12 or Fcε receptor Iγ chain (FcRγ) have been shown to be critical for osteoclast differentiation and maturation under normal physiological conditions. Their function in pathological conditions is unknown. We studied the role of ITAM signaling during rapid bone remodeling induced by acute estrogen-deficiency in wild-type (WT), DAP12-deficient (DAP12-/-), FcRγ-deficient (FcRγ-/-) and double-deficient (DAP12-/-FcRγ-/-) mice. Six weeks after ovariectomy (OVX), DAP12-/-FcRγ-/- mice showed resistance to lumbar vertebral body (LVB) trabecular bone loss, while WT, DAP12-/- and FcRγ-/- mice had significant LVB bone loss. In contrast, all ITAM adapter-deficient mice responded to OVX with bone loss in both femur and tibia of approximately 40%, relative to basal bone volumes. Only WT mice developed significant cortical bone loss after OVX. In vitro studies showed microenvironmental changes induced by OVX are indispensable for enhanced osteoclast formation and function. Cytokine changes, including TGFβ and TNFα, were able to induce osteoclastogenesis independent of RANKL in BMMs from WT but not DAP12-/- and DAP12-/-FcRγ-/- mice. FSH stimulated RANKL-induced osteoclast differentiation from BMMs in WT, but not DAP12-/- and DAP12-/-FcRγ-/- mice. Our study demonstrates that although ITAM adapter signaling is critical for normal bone remodeling, estrogen-deficiency induces an ITAM adapter-independent bypass mechanism allowing for enhanced osteoclastogenesis and activation in specific bony microenvironments. PMID:17611621

  15. CHOP deficiency prevents methylglyoxal-induced myocyte apoptosis and cardiac dysfunction.

    PubMed

    Nam, Dae-Hwan; Han, Jung-Hwa; Lee, Tae-Jin; Shishido, Tetsuro; Lim, Jae Hyang; Kim, Geun-Young; Woo, Chang-Hoon

    2015-08-01

    Epidemiological studies indicate that methylglyoxal (MGO) plasma levels are closely linked to diabetes and the exacerbation of diabetic cardiovascular complications. Recently, it was established that endoplasmic reticulum (ER) stress importantly contributes to the pathogenesis of diabetes and its cardiovascular complications. The objective of this study was to explore the mechanism by which diabetes instigates cardiomyocyte apoptosis and cardiac dysfunction via MGO-mediated myocyte apoptosis. Intriguingly, the MGO activated unfolded protein response pathway accompanying apoptotic events, such as cleavages of PARP-1 and caspase-3. In addition, Western blot analysis revealed that MGO-induced myocyte apoptosis was inhibited by depletion of CHOP with siRNA against Ddit3, the gene name for rat CHOP. To investigate the physiologic roles of CHOP in vivo, glucose tolerance and cardiac dysfunction were assessed in CHOP-deficient mice. No significant difference was observed between CHOP KO and littermate naïve controls in terms of the MGO-induced impairment of glucose tolerance. In contrast, myocyte apoptosis, inflammation, and cardiac dysfunction were significantly diminished in CHOP KO compared with littermate naïve controls. These results showed that CHOP is the key signal for myocyte apoptosis and cardiac dysfunction induced by MGO. These findings suggest a therapeutic potential of CHOP inhibition in the management of diabetic cardiovascular complications including diabetic cardiomyopathy.

  16. Ferric Carboxymaltose-Mediated Attenuation of Doxorubicin-Induced Cardiotoxicity in an Iron Deficiency Rat Model

    PubMed Central

    Toblli, Jorge Eduardo; Rivas, Carlos; Cao, Gabriel; Giani, Jorge Fernando; 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

  17. Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity

    PubMed Central

    Hartmann, Phillipp; Seebauer, Caroline T.; Mazagova, Magdalena; Horvath, Angela; Wang, Lirui; Llorente, Cristina; Varki, Nissi M.; Brandl, Katharina; Ho, Samuel B.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) and obesity are characterized by altered gut microbiota, inflammation, and gut barrier dysfunction. Here, we investigated the role of mucin-2 (Muc2) as the major component of the intestinal mucus layer in the development of fatty liver disease and obesity. We studied experimental fatty liver disease and obesity induced by feeding wild-type and Muc2-knockout mice a high-fat diet (HFD) for 16 wk. Muc2 deficiency protected mice from HFD-induced fatty liver disease and obesity. Compared with wild-type mice, after a 16-wk HFD, Muc2-knockout mice exhibited better glucose homeostasis, reduced inflammation, and upregulated expression of genes involved in lipolysis and fatty acid β-oxidation in white adipose tissue. Compared with wild-type mice that were fed the HFD as well, Muc2-knockout mice also displayed higher intestinal and plasma levels of IL-22 and higher intestinal levels of the IL-22 target genes Reg3b and Reg3g. Our findings indicate that absence of the intestinal mucus layer activates the mucosal immune system. Higher IL-22 levels protect mice from diet-induced features of the metabolic syndrome. PMID:26702135

  18. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis.

    PubMed

    Srinivasan, Gayathri; Aitken, Jesse D; Zhang, Benyue; Carvalho, Frederic A; Chassaing, Benoit; Shashidharamurthy, Rangaiah; Borregaard, Niels; Jones, Dean P; Gewirtz, Andrew T; Vijay-Kumar, Matam

    2012-08-15

    Various states of inflammation, including sepsis, are associated with hypoferremia, which limits iron availability to pathogens and reduces iron-mediated oxidative stress. Lipocalin 2 (Lcn2; siderocalin, 24p3) plays a central role in iron transport. Accordingly, Lcn2-deficient (Lcn2KO) mice exhibit elevated intracellular labile iron. In this study, we report that LPS induced systemic Lcn2 by 150-fold in wild-type mice at 24 h. Relative to wild-type littermates, Lcn2KO mice were markedly more sensitive to endotoxemia, exhibiting elevated indices of organ damage (transaminasemia, lactate dehydrogenase) and increased mortality. Such exacerbated endotoxemia was associated with substantially increased caspase-3 cleavage and concomitantly elevated immune cell apoptosis. Furthermore, cells from Lcn2KO mice were hyperresponsive to LPS ex vivo, exhibiting elevated cytokine secretion. Additionally, Lcn2KO mice exhibited delayed LPS-induced hypoferremia despite normal hepatic hepcidin expression and displayed decreased levels of the tissue redox state indicators cysteine and glutathione in liver and plasma. Desferroxamine, an iron chelator, significantly protects Lcn2KO mice from LPS-induced toxicity, including mortality, suggesting that Lcn2 may act as an antioxidant in vivo by regulating iron homeostasis. Thus, Lcn2-mediated regulation of labile iron protects the host against sepsis. Its small size and simple structure may make Lcn2 a deployable treatment for sepsis.

  19. dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development.

    PubMed

    Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-02-03

    Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis.

  20. Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity.

    PubMed

    Hartmann, Phillipp; Seebauer, Caroline T; Mazagova, Magdalena; Horvath, Angela; Wang, Lirui; Llorente, Cristina; Varki, Nissi M; Brandl, Katharina; Ho, Samuel B; Schnabl, Bernd

    2016-03-01

    Nonalcoholic fatty liver disease (NAFLD) and obesity are characterized by altered gut microbiota, inflammation, and gut barrier dysfunction. Here, we investigated the role of mucin-2 (Muc2) as the major component of the intestinal mucus layer in the development of fatty liver disease and obesity. We studied experimental fatty liver disease and obesity induced by feeding wild-type and Muc2-knockout mice a high-fat diet (HFD) for 16 wk. Muc2 deficiency protected mice from HFD-induced fatty liver disease and obesity. Compared with wild-type mice, after a 16-wk HFD, Muc2-knockout mice exhibited better glucose homeostasis, reduced inflammation, and upregulated expression of genes involved in lipolysis and fatty acid β-oxidation in white adipose tissue. Compared with wild-type mice that were fed the HFD as well, Muc2-knockout mice also displayed higher intestinal and plasma levels of IL-22 and higher intestinal levels of the IL-22 target genes Reg3b and Reg3g. Our findings indicate that absence of the intestinal mucus layer activates the mucosal immune system. Higher IL-22 levels protect mice from diet-induced features of the metabolic syndrome.

  1. Soleus muscle in glycosylation-deficient muscular dystrophy is protected from contraction-induced injury.

    PubMed

    Gumerson, Jessica D; Kabaeva, Zhyldyz T; Davis, Carol S; Faulkner, John A; Michele, Daniel E

    2010-12-01

    The glycosylation of dystroglycan is required for its function as a high-affinity laminin receptor, and loss of dystroglycan glycosylation results in congenital muscular dystrophy. The purpose of this study was to investigate the functional defects in slow- and fast-twitch muscles of glycosylation-deficient Large(myd) mice. While a partial alteration in glycosylation of dystroglycan in heterozygous Large(myd/+) mice was not sufficient to alter muscle function, homozygous Large(myd/myd) mice demonstrated a marked reduction in specific force in both soleus and extensor digitorum longus (EDL) muscles. Although EDL muscles from Large(myd/myd) mice were highly susceptible to lengthening contraction-induced injury, Large(myd/myd) soleus muscles surprisingly showed no greater force deficit compared with wild-type soleus muscles even after five lengthening contractions. Despite no increased susceptibility to injury, Large(myd/myd) soleus muscles showed loss of dystroglycan glycosylation and laminin binding activity and dystrophic pathology. Interestingly, we show that soleus muscles have a markedly higher sarcolemma expression of β(1)-containing integrins compared with EDL and gastrocnemius muscles. Therefore, we conclude that β(1)-containing integrins play an important role as matrix receptors in protecting muscles containing slow-twitch fibers from contraction-induced injury in the absence of dystroglycan function, and that contraction-induced injury appears to be a separable phenotype from the dystrophic pathology of muscular dystrophy.

  2. Epigenetic Upregulation of Corticotrophin-Releasing Hormone Mediates Postnatal Maternal Separation-Induced Memory Deficiency

    PubMed Central

    Wang, Aiyun; Nie, Wenying; Li, Haixia; Hou, Yuhua; Yu, Zhen; Fan, Qing; Sun, Ruopeng

    2014-01-01

    Accumulating evidences demonstrated that early postnatal maternal separation induced remarkable social and memory defects in the adult rodents. Early-life stress induced long-lasting functional adaptation of neuroendocrine hypothalamic-pituitary-adrenal axis, including neuropeptide corticotrophin-releasing hormone (CRH) in the brain. In the present study, a significantly increased hippocampal CRH was observed in the adult rats with postnatal maternal separation, and blockade of CRHR1 signaling significantly attenuated the hippocampal synaptic dysfunction and memory defects in the modeled rats. Postnatal maternal separation enduringly increased histone H3 acetylation and decreased cytosine methylation in Crh promoter region, resulting from the functional adaptation of several transcriptional factors, in the hippocampal CA1 of the modeled rats. Enriched environment reversed the epigenetic upregulation of CRH, and ameliorated the hippocampal synaptic dysfunction and memory defects in the adult rats with postnatal maternal separation. This study provided novel insights into the epigenetic mechanism underlying postnatal maternal separation-induced memory deficiency, and suggested environment enrichment as a potential approach for the treatment of this disorder. PMID:24718660

  3. The Protective Effect of Yi Shen Juan Bi Pill in Arthritic Rats with Castration-Induced Kidney Deficiency

    PubMed Central

    Zhao, Hongyan; Li, Jian; He, Xiaojuan; Lu, Cheng; Xiao, Cheng; Niu, Xuyan; Zhao, Ning; Ju, Dahong; Lu, Aiping

    2012-01-01

    Androgens have been linked to the onset, severity, and progression of rheumatoid arthritis (RA). In traditional Chinese medicine (TCM), the most common pattern in RA is kidney deficiency, which partly corresponds to a low sex hormone state. In this study, TCM kidney deficiency was induced in male Sprague-Dawley rats with castration surgery, and a TCM preparation, Yi Shen Juan Bi Pill (YJB), was used to treat collagen induced arthritis (CIA) rats with castration. Metabolomic technique was used to evaluate the pharmacological mechanism in castrated CIA rats treated by YJB. The results showed that castration significantly increased the severity of the arthritis in rats but was ameliorated by YJB. Its pharmacological mechanism was partially associated with lipid metabolites involving free fatty acid (FFA) and lysophosphatidylcholine (LPC). In conclusion, the experimental results demonstrate the protective effect of YJB on the TCM kidney deficiency pattern induced by androgen deficiency in CIA rats and support that YJB should be used for the clinical treatment of RA with TCM kidney deficiency pattern. PMID:22550538

  4. Low Urinary Iodine Concentration among Mothers and Children in Cambodia

    PubMed Central

    Laillou, Arnaud; Sophonneary, Prak; Kuong, Khov; Hong, Rathavuth; Un, Samoeurn; Chamnan, Chhoun; Poirot, Etienne; Berger, Jacques; Wieringa, Frank

    2016-01-01

    A 2014 national assessment of salt iodization coverage in Cambodia found that 62% of samples were non-iodized, suggesting a significant decline in daily iodine intakes. The Cambodian Micronutrient Survey conducted in 2014 (CMNS-2014) permitted obtaining national data on urinary iodine concentrations (UIC) to assess iodine status and whether iodized salt use had an impact. Urine samples were collected from mothers (n = 736) and children (n = 950). The median UIC was 63 µg/L and 72 µg/L in mothers and children respectively. More than 60% of mothers and their children had a UIC < 100 µg/L, thereby indicating a serious public health problem. Iodine status was significantly lower among mothers and children living in rural areas, belonging to the poorest socioeconomic category, or living in a household not using iodized salt. The limited enforcement of the legislation for iodized salt has resulted in a major decrease in the prevalence of iodized salt, which in turn has compromised iodine status in Cambodia. It is essential for the government to enhance enforcement of the iodized salt legislation, and implement short term strategies, such as iodine supplementation, to prevent an increase of severe complications due to iodine deficiency in the Cambodian population. PMID:27058551

  5. 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

  6. Permeation of iodide from iodine-enriched yeast through porcine intestine.

    PubMed

    Ryszka, Florian; Dolińska, Barbara; Zieliński, Michał; Chyra, Dagmara; Dobrzański, Zbigniew

    2013-01-01

    Iodine deficiency is a common phenomenon, threatening the whole global human population. Recommended daily intake of iodine is 150 μg for adults and 250 μg for pregnant and breastfeeding women. About 50% of human population can be at risk of moderate iodine deficiency. Due to this fact, increased iodine supplementation is recommended, through intake of iodized mineral water and salt iodization. The aim of this study was to investigate permeation and absorption of iodide from iodine bioplex (experimental group) in comparison with potassium iodide (controls). Permeation and absorption processes were investigated in vitro using a porcine intestine. The experimental model was based on a standard Franz diffusion cell (FD-Cell). The iodine bioplex was produced using Saccharomyces cerevisiae yeast and whey powder: iodine content - 388 μg/g, total protein - 28.5%, total fat - 0.9%., glutamic acid - 41.2%, asparaginic acid - 29.4%, lysine - 24.8%; purchased from: F.Z.N.P. Biochefa, Sosnowiec, Poland. Potassium iodide was used as controls, at 388 μg iodine concentration, which was the same as in iodine-enriched yeast bioplex. A statistically significant increase in iodide permeation was observed for iodine-enriched yeast bioplex in comparison with controls - potassium iodide. After 5h the total amount of permeated iodide from iodine-enriched yeast bioplex was 85%, which is ~ 2-fold higher than controls - 37%. Iodide absorption was by contrast statistically significantly higher in controls - 7.3%, in comparison with 4.5% in experimental group with iodine-enriched yeast bioplex. Presented results show that iodide permeation process dominates over absorption in case of iodine-enriched yeast bioplex.

  7. Insulin-like growth factor 1 deficiency exacerbates hypertension-induced cerebral microhemorrhages in mice, mimicking the aging phenotype.

    PubMed

    Tarantini, Stefano; Valcarcel-Ares, Noa M; Yabluchanskiy, Andriy; Springo, Zsolt; Fulop, Gabor A; Ashpole, Nicole; Gautam, Tripti; Giles, Cory B; Wren, Jonathan D; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2017-03-14

    Clinical and experimental studies show that aging exacerbates hypertension-induced cerebral microhemorrhages (CMHs), which progressively impair neuronal function. There is growing evidence that aging promotes insulin-like growth factor 1 (IGF-1) deficiency, which compromises multiple aspects of cerebromicrovascular and brain health. To determine the role of IGF-1 deficiency in the pathogenesis of CMHs, we induced hypertension in mice with liver-specific knockdown of IGF-1 (Igf1(f/f)  + TBG-Cre-AAV8) and control mice by angiotensin II plus l-NAME treatment. In IGF-1-deficient mice, the same level of hypertension led to significantly earlier onset and increased incidence and neurological consequences of CMHs, as compared to control mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Previous studies showed that in aging, increased oxidative stress-mediated matrix metalloprotease (MMP) activation importantly contributes to the pathogenesis of CMHs. Thus, it is significant that hypertension-induced cerebrovascular oxidative stress and MMP activation were increased in IGF-1-deficient mice. We found that IGF-1 deficiency impaired hypertension-induced adaptive media hypertrophy and extracellular matrix remodeling, which together with the increased MMP activation likely also contributes to increased fragility of intracerebral arterioles. Collectively, IGF-1 deficiency promotes the pathogenesis of CMHs, mimicking the aging phenotype, which likely contribute to its deleterious effect on cognitive function. Therapeutic strategies that upregulate IGF-1 signaling in the cerebral vessels and/or reduce microvascular oxidative stress, and MMP activation may be useful for the prevention of CMHs, protecting cognitive function in high-risk elderly patients.

  8. Iodine chemical forms in LWR severe accidents

    SciTech Connect

    Weber, C.F.; Beahm, E.C.; Kress, T.S.

    1991-01-01

    Calculated data from seven severe accident sequences in light water reactor plants were used to assess the chemical forms of iodine in containment. In most of the calculations for the seven sequences, iodine entering containment from the reactor coolant system was almost entirely in the form of CsI with very small contributions of I or HI. The largest fraction of iodine in forms other than CsI was a total of 3.2% as I plus HI. Within the containment, the CsI will deposit onto walls and other surfaces, as well as in water pools, largely in the form of iodide (I{sup {minus}}). The radiation-induced conversion of I{sup {minus}} in water pools into I{sub 2} is strongly dependent on pH. In systems where the pH was controlled above 7, little additional elemental iodine would be produced in the containment atmosphere. When the pH falls below 7, it may be assumed that it is not being controlled and large fractions of iodine as I{sub 2} within the containment atmosphere may be produced. 17 refs., 5 tabs.

  9. Iodine chemical forms in LWR severe accidents

    SciTech Connect

    Beahm, E.C.; Weber, C.F.; Kress, T.S.; Parker, G.W.

    1991-01-01

    Calculated data from seven severe accident sequences in light-water reactor plants were used to assess the chemical forms of iodine in containment. In most of the calculations for the seven sequences, iodine entering containment from the reactor coolant system was almost entirely in the form of CsI with very small contributions of I or HI. The largest fraction of iodine in forms other than CsI was a total of 3.2% as I plus HI. Within the containment, the CsI will deposit onto walls and other surfaces, as well as in water pools, largely in the form of iodide (I{sup {minus}}). The radiation induced conversion of I{sup {minus}} in water pools into I{sub 2} is strongly dependent on pH. In systems where the pH was controlled above 7, little additional elemental iodine would be produced in the containment atmosphere. When the pH falls below 7, it may be assumed that it is not being controlled, and large fractions of iodine as I{sub 2} within the containment atmosphere may be produced. 16 refs.

  10. Feasibility of ultra-trace determination of bromine and iodine in honey by ICP-MS using high sample mass in microwave-induced combustion.

    PubMed

    Costa, Vanize C; Picoloto, Rochele S; Hartwig, Carla A; Mello, Paola A; Flores, Erico M M; Mesko, Marcia F

    2015-10-01

    This work demonstrates the feasibility of ultra-trace determination of halogens in biological samples by inductively coupled plasma mass spectrometry (ICP-MS) after decomposition by microwave-induced combustion (MIC). The conventional MIC method was improved to allow the combustion of samples with mass higher than that used in previous works in order to achieve better limits of detection (LODs). The applicability of the proposed method for ultra-trace determination of bromine and iodine in organic samples was demonstrated here using honey. It was possible to decompose up to 1000 mg of honey using microcrystalline cellulose as a combustion aid and polyethylene film for sample wrapping. After combustion, analytes were absorbed using 50 mmol L(-1) NH4OH and recoveries for Br and I were between 99 and 104 %, and relative standard deviations were lower than 5 %. Microwave-assisted alkaline dissolution (MA-AD) was also evaluated for honey sample preparation using NH4OH or tetramethylammonium hydroxide solutions. However, the LODs for the MA-AD method were unsuitable because the high carbon content in digests required a dilution step prior to the analysis by ICP-MS. The LODs obtained by MIC were improved from 1143 to 34 ng g(-1) for Br and from 571 to 6.0 ng g(-1) for I, when compared to the MA-AD method. Furthermore, it was possible to decompose up to eight samples simultaneously in 30 min (including the cooling step) with very low reagent consumption and consequently lower generation of effluents, making MIC method well suited for routine ultra-trace determination of Br and I in honey. Graphical Abstract A high mass of honey was efficiently digested by MIC for subsequent Br and I determination by ICP-MS.

  11. Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout.

    PubMed

    Zanzonico, P B; Becker, D V

    2000-06-01

    Radioiodines, particularly 131I, may be released into the environment in breach-of-containment nuclear reactor accidents and localize in and irradiate the thyroid with an attendant risk of neoplastic growth and other adverse health effects. Pharmacologic thyroid blockade by oral potassium iodide (KI) (50-100 mg in adults) can substantially reduce thyroid uptake of and irradiation by internalized radioiodine. In the current analysis, computer modeling of iodine metabolism has been used to systematically elucidate the effects of two practically important but highly variable factors on the radioprotective effect of KI: the time of administration relative to exposure to radioiodine and the dietary level of iodine. In euthyroid adults receiving iodine-sufficient diets (250 microg d(-1) in the current analysis), KI administered up to 48 h before 131I exposure can almost completely block thyroid uptake and therefore greatly reduce the thyroid absorbed dose. However, KI administration 96 h or more before 131I exposure has no significant protective effect. In contrast, KI administration after exposure to radioiodine induces a smaller and rapidly decreasing blockade effect. KI administration 16 h or later after 131I exposure will have little effect on thyroid uptake and absorbed dose and therefore little or no protective effect. The 131I thyroid absorbed dose is two-fold greater with insufficient levels of dietary iodine, 2,900 cGy/37 MBq, than with sufficient levels of dietary iodine, 1,500 cGy/37 MBq. When KI is administered 48 h or less before 131I intake, the thyroid absorbed doses (in cGy/37 MBq) are comparably low with both sufficient and insufficient dietary iodine levels. When KI is administered after 131I intake, however, the protective effect of KI is less and decreases more rapidly with insufficient than with sufficient dietary iodine. For example, KI administration 2 and 8 h after 131I intake yields protective effects of 80 and 40%, respectively, with iodine

  12. The Pathogenesis of Ethanol versus Methionine and Choline Deficient Diet-Induced Liver Injury

    PubMed Central

    Gyamfi, Maxwell Afari; Damjanov, Ivan; French, Samuel; Wan, Yu-Jui Yvonne

    2008-01-01

    The differences and similarities of the pathogenesis of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH) were examined. Mice (6/group) received 1 of 4 Lieber-Decarli liquid diets for 6 weeks: (1) paired-fed control diet; (2) control diet with ethanol (ethanol); (3) paired-fed methionine/choline deficient (MCD) diet; and (4) MCD plus ethanol (combination). Hepatotoxicity, histology, and gene expression changes were examined. Both MCD and ethanol induced macrovesicular steatosis. However, the combination diet produced massive steatosis with minor necrosis and inflammation. MCD and combination diets, but not ethanol, induced serum ALT levels by 1.6- and 10-fold, respectively. MCD diet, but not ethanol, also induced serum alkaline phosphatase levels suggesting bile duct injury. Ethanol increased liver fatty acid binding protein (L-FABP) mRNA and protein levels. In contrast, the combination diet decreased L-FABP mRNA and protein levels and increased hepatic free fatty acid and lipid peroxide levels. Ethanol, but not MCD, reduced hepatic S-adenosylmethionine (SAM) and GSH levels. Hepatic TNFα protein levels were increased in all treatment groups, however, IL-6, a hepatoprotective cytokine which promotes liver regeneration was increased in ethanol-fed mice (2-fold), but decreased in the combination diet-treated mice. In addition, the combination diet reduced phosphorylated STAT3 and Bcl-2 levels. While MCD diet might cause bile duct injury and cholestasis, ethanol preferentially interferes with the SAM-GSH oxidative stress pathway. The exacerbated liver injury induced by the combination diet might be explained by reduced L-FABP, increased free fatty acids, oxidative stress, and decreased IL-6 protein levels. The combination diet is an efficient model of steatohepatitis. PMID:18036573

  13. Dependence of the molecular iodine B-state predissociation induced by a femtosecond laser pulse on pulse phase modulation

    SciTech Connect

    Kostyukevich, Yu I; Umanskii, Stanislav Ya

    2011-12-31

    The processes of pumping and laser-induced predissociation of B-states of the I{sub 2} molecule under the action of femtosecond laser pulses are considered theoretically. An analytical formula is derived, which describes the dependence of the predissociation on such parameters of femtosecond pulses as spectral chirp, spectral width and delay time between pulses. The formula is used to calculate numerically the dependence of the predissociation yield on the parameters of the phase modulation of the pump pulse and coupling pulse.

  14. Iodine nutrition in pregnancy and lactation.

    PubMed

    Leung, Angela M; Pearce, Elizabeth N; Braverman, Lewis E

    2011-12-01

    Adequate iodine intake is required for the synthesis of thyroid hormones that are important for normal fetal and infant neurodevelopment. In this review, we discuss iodine physiology during pregnancy and lactation, methods to assess iodine sufficiency, the importance of adequate iodine nutrition, studies of iodine supplementation during pregnancy and lactation, the consequences of hypothyroidism during pregnancy, the current status of iodine nutrition in the United States, the global efforts toward achieving universal iodine sufficiency, and substances that may interfere with iodine use.

  15. 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.

  16. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis.

    PubMed

    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.

  17. Plasmid-deficient Chlamydia muridarum fail to induce immune pathology and protect against oviduct disease.

    PubMed

    O'Connell, Catherine M; Ingalls, Robin R; Andrews, Charles W; Scurlock, Amy M; Darville, Toni

    2007-09-15

    Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection in the world. In women, genital infection can cause endometritis and pelvic inflammatory disease with the severe sequelae of ectopic pregnancy or infertility. Chlamydia sp. do not damage tissues directly, but induce an injurious host inflammatory response at the infected site. In the murine model of genital disease with Chlamydia muridarum, TLR2 plays a role in both early production of inflammatory mediators and development of chronic oviduct pathology. We report the results of studies with plasmid-cured C. muridarum mutants that retain the ability to infect the murine genital tract, but fail to cause disease in the oviduct. These mutants do not stimulate TLR2-dependent cytokine production in mice, nor in innate immune cells or epithelial cells in vitro. They induce an effective Th1 immune response, with no evidence for Th1-immune-mediated collateral tissue damage. Furthermore, mice previously infected with the plasmid-deficient strains are protected against oviduct disease upon challenge with virulent C. muridarum. If plasmid-cured derivatives of human C. trachomatis biovars exhibit similar phenotypic characteristics, they have the potential to serve as vaccines to prevent human disease.

  18. Notch Downregulation and Extramedullary Erythrocytosis in Hypoxia-Inducible Factor Prolyl 4-Hydroxylase 2-Deficient Mice.

    PubMed

    Myllymäki, Mikko N M; Määttä, Jenni; Dimova, Elitsa Y; Izzi, Valerio; Väisänen, Timo; Myllyharju, Johanna; Koivunen, Peppi; Serpi, Raisa

    2017-01-15

    Erythrocytosis is driven mainly by erythropoietin, which is regulated by hypoxia-inducible factor (HIF). Mutations in HIF prolyl 4-hydroxylase 2 (HIF-P4H-2) (PHD2/EGLN1), the major downregulator of HIFα subunits, are found in familiar erythrocytosis, and large-spectrum conditional inactivation of HIF-P4H-2 in mice leads to severe erythrocytosis. Although bone marrow is the primary site for erythropoiesis, spleen remains capable of extramedullary erythropoiesis. We studied HIF-P4H-2-deficient (Hif-p4h-2(gt/gt)) mice, which show slightly induced erythropoiesis upon aging despite nonincreased erythropoietin levels, and identified spleen as the site of extramedullary erythropoiesis. Splenic hematopoietic stem cells (HSCs) of these mice exhibited increased erythroid burst-forming unit (BFU-E) growth, and the mice were protected against anemia. HIF-1α and HIF-2α were stabilized in the spleens, while the Notch ligand genes Jag1, Jag2, and Dll1 and target Hes1 became downregulated upon aging HIF-2α dependently. Inhibition of Notch signaling in wild-type spleen HSCs phenocopied the increased BFU-E growth. HIFα stabilization can thus mediate non-erythropoietin-driven splenic erythropoiesis via altered Notch signaling.

  19. Bile Duct Ligation Induces ATZ Globule Clearance In a Mouse Model of Alpha-1 Antitrypsin Deficiency

    PubMed Central

    Khan, Zahida; Yokota, Shinichiro; Ono, Yoshihiro; Bell, Aaron W.; Stolz, Donna B.; Michalopoulos, George K.

    2016-01-01

    Background Alpha-1 antitrypsin deficiency (A1ATD) can progress to cirrhosis and hepatocellular carcinoma; however, not all patients are susceptible to severe liver disease. In A1ATD, a toxic gain-of-function mutation generates insoluble ATZ “globules” in hepatocytes, overwhelming protein clearance mechanisms. The relationship between bile acids and hepatocytic autophagy is less clear, but may involve altered gene expression pathways. Based on previous findings that bile duct ligation (BDL) induces autophagy, we hypothesized that retained bile acids may have hepatoprotective effects in PiZZ transgenic mice, which model A1ATD. Methods We performed BDL and partial BDL (pBDL) in PiZZ mice, followed by analysis of liver tissues. Results PiZZ liver subjected to BDL showed up to 50% clearance of ATZ globules, with increased expression of autophagy proteins. Analysis of transcription factors revealed significant changes. Surprisingly nuclear TFEB, a master regulator of autophagy, remained unchanged. pBDL confirmed that ATZ globule clearance was induced by localized stimuli rather than diet or systemic effects. Several genes involved in bile metabolism were over-expressed in globule-devoid hepatocytes, compared to globule-containing cells. Conclusions Retained bile acids led to a dramatic reduction of ATZ globules, with enhanced hepatocyte regeneration and autophagy. These findings support investigation of synthetic bile acids as potential autophagy-enhancing agents. PMID:27938510

  20. The influence of experimentally induced copper deficiency on the fertility of rams. I. Semen parameters and peripheral plasma androgen concentration.

    PubMed

    Van Niekerk, F E; Van Niekerk, C H

    1989-03-01

    The influence of molybdenum and molybdenum plus sulphate-induced copper deficiencies on semen quality and peripheral plasma testosterone concentrations in South African Mutton Merino rams was investigated. All animals received an identical ration, supplemented with molybdenum in one group (M) and molybdenum plus sulphate in another (MS) while the control group (C) received additional copper supplementation. After almost a year on these rations, rams in Group MS produced ejaculates of lower volume, lower sperm concentration, poorer sperm motility and morphology than rams of the other 2 groups. The fructose concentration in the ejaculates of group MS rams was also lower than that of rams in the other groups. Peripheral plasma testosterone concentrations in Group MS were lower than in Groups C or M. Liver copper concentrations and clinical signs were consistent with a severe copper deficiency in Group MS and a mild deficiency in Group M. After the copper deficiency was reversed, the above parameters reverted to normal. It was concluded that an experimentally induced copper deficiency produced reversible impairment of testicular function in rams.

  1. Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice.

    PubMed

    Carrasco, J; Penkowa, M; Hadberg, H; Molinero, A; Hidalgo, J

    2000-07-01

    Metallothioneins (MTs) are major zinc binding proteins in the CNS that could be involved in the control of zinc metabolism as well as in protection against oxidative stress. Mice lacking MT-I and MT-II (MT-I + II deficient) because of targeted gene inactivation were injected with kainic acid (KA), a potent convulsive agent, to examine the neurobiological importance of these MT isoforms. At 35 mg/kg KA, MT-I + II deficient male mice showed a higher number of convulsions and a longer convulsion time than control mice. Three days later, KA-injected mice showed gliosis and neuronal injury in the hippocampus. MT-I + II deficiency decreased both astrogliosis and microgliosis and potentiated neuronal injury and apoptosis as shown by terminal deoxynucleotidyl transferase-mediated in situ end labelling (TUNEL), detection of single stranded DNA (ssDNA) and by increased interleukin-1beta-converting enzyme (ICE) and caspase-3 levels. Histochemically reactive zinc in the hippocampus was increased by KA to a greater extent in MT-I + II-deficient compared with control mice. KA-induced seizures also caused increased oxidative stress, as suggested by the malondialdehyde (MDA) and protein tyrosine nitration (NITT) levels and by the expression of MT-I + II, nuclear factor-kappaB (NF-kappaB), and Cu/Zn-superoxide dismutase (Cu/Zn-SOD). MT-I + II deficiency potentiated the oxidative stress caused by KA. Both KA and MT-I + II deficiency significantly affected the expression of MT-III, granulocyte-macrophage colony stimulating factor (GM-CSF) and its receptor (GM-CSFr). The present results indicate MT-I + II as important for neuron survival during KA-induced seizures, and suggest that both impaired zinc regulation and compromised antioxidant activity contribute to the observed neuropathology of the MT-I + II-deficient mice.

  2. 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

  3. Loss of TLR2 Worsens Spontaneous Colitis in MDR1A Deficiency through Commensally Induced Pyroptosis

    PubMed Central

    Ey, Birgit; Eyking, Annette; Klepak, Magdalena; Salzman, Nita H.; Göthert, Joachim R.; Rünzi, Michael; Schmid, Kurt W.; Gerken, Guido; Podolsky, Daniel K.

    2013-01-01

    Variants of the multidrug resistance gene (MDR1/ABCB1) have been associated with increased susceptibility to severe ulcerative colitis (UC). In this study, we investigated the role of TLR/IL-1R signaling pathways including the common adaptor MyD88 in the pathogenesis of chronic colonic inflammation in MDR1A deficiency. Double- or triple-null mice lacking TLR2, MD-2, MyD88, and MDR1A were generated in the FVB/N background. Deletion of TLR2 in MDR1A deficiency resulted in fulminant pancolitis with early expansion of CD11b+ myeloid cells and rapid shift toward TH1-dominant immune responses in the lamina propria. Colitis exacerbation in TLR2/MDR1A double-knockout mice required the unaltered commensal microbiota and the LPS coreceptor MD-2. Blockade of IL-1β activity by treatment with IL-1R antagonist (IL-1Ra; Anakinra) inhibited colitis acceleration in TLR2/MDR1A double deficiency; intestinal CD11b+Ly6C+-derived IL-1β production and inflammation entirely depended on MyD88. TLR2/MDR1A double-knockout CD11b+ myeloid cells expressed MD-2/TLR4 and hyperresponded to nonpathogenic Escherichia coli or LPS with reactive oxygen species production and caspase-1 activation, leading to excessive cell death and release of proinflammatory IL-1β, consistent with pyroptosis. Inhibition of reactive oxygen species–mediated lysosome degradation suppressed LPS hyperresponsiveness. Finally, active UC in patients carrying the TLR2-R753Q and MDR1-C3435T polymorphisms was associated with increased nuclear expression of caspase-1 protein and cell death in areas of acute inflammation, compared with active UC patients without these variants. In conclusion, we show that the combined defect of two UC susceptibility genes, MDR1A and TLR2, sets the stage for spontaneous and uncontrolled colitis progression through MD-2 and IL-1R signaling via MyD88, and we identify commensally induced pyroptosis as a potential innate immune effector in severe UC pathogenesis. PMID:23636052

  4. 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

  5. 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

  6. Cyclooxygenase-2 deficiency exacerbates bleomycin-induced lung dysfunction but not fibrosis.

    PubMed

    Card, Jeffrey W; Voltz, James W; Carey, Michelle A; Bradbury, J Alyce; Degraff, Laura M; Lih, Fred B; Bonner, James C; Morgan, Daniel L; Flake, Gordon P; Zeldin, Darryl C

    2007-09-01

    Cyclooxygenase (COX)-derived eicosanoids have been implicated in the pathogenesis of pulmonary fibrosis. Uncertainty regarding the influence of COX-2 on experimental pulmonary fibrosis prompted us to clarify the fibrotic and functional effects of intratracheal bleomycin administration in mice genetically deficient in COX-2. Further, the effects of airway-specific COX-1 overexpression on fibrotic and functional outcomes in wild-type and COX-2 knockout mice were assessed. Equivalent increases in airway cell influx, lung collagen content, and histopathologic evidence of fibrosis were observed in wild-type and COX-2 knockout mice 21 d after bleomycin treatment, suggesting that COX-2 deficiency did not alter the extent or severity of fibrosis in this model. However, bleomycin-induced alterations in respiratory mechanics were more severe in COX-2 knockout mice than in wild-type mice, as illustrated by a greater decrease in static compliance compared with genotype-matched, saline-treated control mice (26 +/- 3% versus 11 +/- 4% decreases for COX-2 knockout and wild-type mice, respectively; P < 0.05). The influence of COX-1 overexpression in airway Clara cells was also examined. Whereas the fibrotic effects of bleomycin were not altered in wild-type or COX-2 knockout mice overexpressing COX-1, the exaggerated lung function decrement in bleomycin-treated COX-2 knockout mice was prevented by COX-1 overexpression and coincided with decreased airway cysteinyl leukotriene levels. Collectively, these data suggest an important regulatory role for COX-2 in the maintenance of lung function in the setting of lung fibrosis, but not in the progression of the fibrotic process per se.

  7. 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

  8. ADAMTS13 deficiency promotes microthrombosis in a murine model of diet-induced liver steatosis.

    PubMed

    Geys, Lotte; Bauters, Dries; Roose, Elien; Tersteeg, Claudia; Vanhoorelbeke, Karen; Hoylaerts, Marc F; Lijnen, Roger H; Scroyen, Ilse

    2017-01-05

    ADAMTS13 cleaves ultralarge multimeric von Willebrand Factor (VWF), thereby preventing formation of platelet-rich microthrombi. ADAMTS13 is mainly produced by hepatic stellate cells, and numerous studies have suggested a functional role of ADAMTS13 in the pathogenesis of liver diseases. The aim of our study was to investigate a potential role of ADAMTS13 in formation of hepatic microthrombi and development of non-alcoholic steatohepatitis (NASH), and furthermore to evaluate whether plasmin can compensate for the absence of ADAMTS13 in removal of thrombi. Therefore, we used a model of high-fat diet-induced steatosis in Adamts13 deficient (Adamts13(-/-)) and wild-type (WT) control mice. Microthrombi were more abundant in the liver of obese Adamts13(-/-) as compared to obese WT or to lean Adamts13(-/-) mice. Obese Adamts13(-/-) mice displayed lower platelet counts and higher prevalence of ultra-large VWF multimers. Hepatic plasmin-α2-antiplasmin complex levels were comparable for obese WT and Adamts13(-/-) mice and were lower for lean Adamts13(-/-) than WT mice, not supporting marked activation of the fibrinolytic system. High fat diet feeding, as compared to normal chow, resulted in enhanced liver triglyceride levels for both genotypes (p < 0.0001) and steatosis (p < 0.0001 for WT mice, p = 0.002 for Adamts13(-/-) mice) without differences between the genotypes. Expression of markers of inflammation, oxidative stress, steatosis and fibrosis was affected by diet, but not by genotype. Thus, our data confirm that obesity promotes NASH, but do not support a detrimental role of ADAMTS13 in its development. However, Adamts13 deficiency in obese mice promotes hepatic microthrombosis, whereas a compensatory role of plasmin in removal of microthrombi in the absence of ADAMTS13 could not be demonstrated.

  9. Strigolactones are required for nitric oxide to induce root elongation in response to nitrogen and phosphate deficiencies in rice.

    PubMed

    Sun, Huwei; Bi, Yang; Tao, Jinyuan; Huang, Shuangjie; Hou, Mengmeng; Xue, Ren; Liang, Zhihao; Gu, Pengyuan; Yoneyama, Koichi; Xie, Xiaonan; Shen, Qirong; Xu, Guohua; Zhang, Yali

    2016-07-01

    The response of the root system architecture to nutrient deficiencies is critical for sustainable agriculture. Nitric oxide (NO) is considered a key regulator of root growth, although the mechanisms remain unknown. Phenotypic, cellular and genetic analyses were undertaken in rice to explore the role of NO in regulating root growth and strigolactone (SL) signalling under nitrogen-deficient and phosphate-deficient conditions (LN and LP). LN-induced and LP-induced seminal root elongation paralleled NO production in root tips. NO played an important role in a shared pathway of LN-induced and LP-induced root elongation via increased meristem activity. Interestingly, no responses of root elongation were observed in SL d mutants compared with wild-type plants, although similar NO accumulation was induced by sodium nitroprusside (SNP) application. Application of abamine (the SL inhibitor) reduced seminal root length and pCYCB1;1::GUS expression induced by SNP application in wild type; furthermore, comparison with wild type showed lower SL-signalling genes in nia2 mutants under control and LN treatments and similar under SNP application. Western blot analysis revealed that NO, similar to SL, triggered proteasome-mediated degradation of D53 protein levels. Therefore, we presented a novel signalling pathway in which NO-activated seminal root elongation under LN and LP conditions, with the involvement of SLs.

  10. [Iodinated contrast media and iodine allergy: myth or reality?].

    PubMed

    Meunier, B; Joskin, J; Damas, F; Meunier, P

    2013-09-01

    The term "iodine allergy" is an old phrase that refers to a reaction to iodinated contrast media. After a brief review of definitions, pathophysiological mechanisms and risk factors of this clinical entity, management is urged immediate and delayed according to the most recent recommendations from the literature. We underline that iodine allergy, as such, does not really exist.

  11. 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.

  12. Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

    PubMed

    Heo, Jung-Yoon; Cha, Hye-Na; Kim, Ki Young; Lee, Eujin; Kim, Suk-Jeong; Kim, Yong-Woon; Kim, Jong-Yeon; Lee, In-Kyu; Gladyshev, Vadim N; Kim, Hwa-Young; Park, So-Young

    2017-01-01

    Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

  13. 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

  14. Volatilization of iodine from vegetation

    NASA Astrophysics Data System (ADS)

    Amiro, B. D.; Johnston, F. L.

    Gaseous emissions of iodine were measured from bean plant foliage. A gamma-emitting iodine tracer, Na 125I, was taken up by the plants from a hydroponic growth medium and released to a cuvette atmosphere. The dynamics of the flux were studied using a flow-through gamma detector. The relationship between leaf radioactive tracer activity and growth-medium activity was linear, as was the relationship between the iodine flux and both leaf and growth-medium activity. Iodine flux and leaf conductance to water responded similarly to changes in light levels, suggesting that the stomata may partially control the flux. The flux was inhibited by aeration of the hydroponic growth medium, and we postulate that methylation causes the iodine flux. Iodine emissions from living vegetation probably contribute <0.1 % to the stable iodine concentration in the atmosphere above terrestrial areas. However, this pathway may be a direct route for radioactive iodine transport from contaminated soils to the atmosphere.

  15. Stability of iodine during cooking: investigation on biofortified and not fortified vegetables.

    PubMed

    Comandini, Patrizia; Cerretani, Lorenzo; Rinaldi, Massimiliano; Cichelli, Angelo; Chiavaro, Emma

    2013-11-01

    Biofortification of food crops through fertilization and salt iodization are key strategies for the prevention and control of iodine deficiency disorder. However, considerable losses of iodine can occur during processing. In this study, the stability of iodine in biofortified potatoes, carrots and tomatoes was evaluated during different domestic cooking procedures, as this matter was poorly discussed in literature. The stability of iodized salt during baking and boiling of carrots and potatoes not fortified was also investigated. All the adopted cooking procedures have proven to be suitable to preserve the iodine content in biofortified vegetables. During boiling test with iodized salt, neither potatoes nor carrots were able to absorb iodine added with salt, probably owing to the losses occurred during cooking. On the contrary, baking test on potatoes has not caused a significant degradation of iodized salt, and no significant differences in iodine concentration were detected before and after cooking.

  16. Abrogation of hybrid resistance to bone marrow engraftment by graft versus host induced immune deficiency

    SciTech Connect

    Hakim, F.T.; Shearer, G.M.

    1986-03-01

    Lethally irradiated F/sub 1/ mice, heterozygous at the hematopoietic histocompatibility (Hh) locus at H-2D/sup b/, reject bone marrow grafts from homozygous H-2/sup b/ parents. This hybrid resistance (HR) is reduced by prior injection of H-2/sup b/ parental spleen cells. Since injection of parental spleen cells produces a profound suppression of F/sub 1/ immune functions, the authors investigated whether parental-induced abrogation of HR was due to graft-vs-host induced immune deficiency (GVHID). HR was assessed by quantifying engraftment in irradiated mice using /sup 125/I-IUdR spleen uptake; GVHID by measuring generation of cytotoxic T lymphocytes (CTL) from unirradiated mice. They observed correlation in time course, spleen dose dependence and T cell dependence between GVHID and loss of HR. The injection of B10 recombinant congenic spleens into (B10 x B10.A) F/sub 1/ mice, prior to grafting with B10 marrow, demonstrated that only those disparities in major histocompatibility antigens which generated GVHID would result in loss of HR. Spleens from (B10 x B10.A(2R))F/sub 1/ mice (Class I disparity only) did not induce GVHID or affect HR, while (B10 x B10.A(5R)F/sub 1/ spleens (Class I and II disparity) abrogated CTL generation and HR completely. GVHID produced by a Class II only disparity, as in (B10 x B10.A(5R))F/sub 1/ spleens injected into (B6/sup bm12 x B10.A(5R))F/sub 1/ mice, was also sufficient to markedly reduce HR to B10 bone marrow. Modulation of hematopoietic graft rejection by GVHID may affect marrow engraftment in man.

  17. 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.

  18. Aqueous chemistry of iodine

    SciTech Connect

    Toth, L.M.; Pannell, K.D.; Kirkland, O.L.

    1984-01-01

    The chemistry of iodine has been examined in aqueous solutions of pH 6 to 10 containing 2500 ppM boron as H/sub 3/BO/sub 3/ at temperatures up to 150/sup 0/C using absorption spectrophotometry to identify and monitor the iodine species present. Kinetic rate constants for the disproportionation of the HOI intermediate, 3HOI= IO/sub 3//sup -/ + 2I/sup -/ + 3H/sup +/, have been measured as a function of pH even though no direct spectral evidence for HOI itself has been observed. An HOI partition coefficient >10/sup 4/ has been estimated; results of ionic strength tests are consistent with HOI being present as an uncharged triatomic species in solution. Redox and radiation effects on the aqueous iodine chemistry have also been described. 11 refs., 2 figs., 3 tabs.

  19. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    SciTech Connect

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. )

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  20. Effect of dietary iodine on production of iodine enriched eggs

    PubMed Central

    Sumaiya, Shaikh; Nayak, Sunil; Baghel, R. P. S.; Nayak, Anju; Malapure, C. D.; Kumar, Rajesh

    2016-01-01

    Aim: Objective of this study was to investigate the effect of different levels of iodine supplementation on iodine content of eggs in laying hens. Materials and Methods: In the experiment, 135 laying hens (White Leghorn) of 55 weeks age were randomly distributed to 5 dietary treatments; each group contained 27 laying hens distributed in three replicates of 9 birds each. Diet T1 was control basal layer diet without iodine enrichment in which iodine content (I2) was as per NRC recommendation. Basal diets were supplemented with calcium iodate (Ca (IO3)2) at 5, 10, 15 and 20 mg/kg in T2, T3, T4 and T5 groups, respectively. The iodine content in the calcium iodate is 65.21%, therefore, the diets T2, T3, T4 and T5 contained 3.25, 6.50, 9.75 and 13.0 ppm iodine, respectively. The laying hens were fed the respective experimental diets ad libitum during the experimental period of 10-week. The iodine content of egg yolk and albumen was analyzed at the end of 5th and 10th week of the experiment. Economics of feeding for the production of iodine enriched egg was calculated at the end of the experiment. Results: Increasing iodine levels in diet of hens from 0.45 to 13.0 ppm significantly increased egg iodine concentration, the highest concentration of egg iodine was observed in the group fed diet supplemented with 13.0 ppm iodine followed by those fed 9.75, 6.50, 3.25 and 0.45 ppm iodine in diet. There was no significant difference in the iodine levels of unboiled versus boiled eggs. Therefore, the consumers are ensured to receive the optimal levels of iodine from boiled iodine-enriched eggs. Among different diets, minimum and significantly lower feeding cost (Rs. per dozen or per kg eggs) was noticed in hens allotted T3 diet (6.50 ppm I2). However, feeding cost of hens receiving 3.25 and 9.25 ppm I2 was statistically (p<0.05) similar to control group (T1). Further, it was noticed that feeding cost (Rs. per dozen or per kg eggs) was significantly increased due to the inclusion

  1. Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice

    PubMed Central

    Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R.; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

    2011-01-01

    Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. PMID:22216345

  2. Development of Standard Reference Materials to support assessment of iodine status for nutritional and public health purposes.

    PubMed

    Long, Stephen E; Catron, Brittany L; Boggs, Ashley Sp; Tai, Susan Sc; Wise, Stephen A

    2016-09-01

    The use of urinary iodine as an indicator of iodine status relies in part on the accuracy of the analytical measurement of iodine in urine. Likewise, the use of dietary iodine intake as an indicator of iodine status relies in part on the accuracy of the analytical measurement of iodine in dietary sources, including foods and dietary supplements. Similarly, the use of specific serum biomarkers of thyroid function to screen for both iodine deficiency and iodine excess relies in part on the accuracy of the analytical measurement of those biomarkers. The National Institute of Standards and Technology has been working with the NIH Office of Dietary Supplements for several years to develop higher-order reference measurement procedures and Standard Reference Materials to support the validation of new routine analytical methods for iodine in foods and dietary supplements, for urinary iodine, and for several serum biomarkers of thyroid function including thyroid-stimulating hormone, thyroglobulin, total and free thyroxine, and total and free triiodothyronine. These materials and methods have the potential to improve the assessment of iodine status and thyroid function in observational studies and clinical trials, thereby promoting public health efforts related to iodine nutrition.

  3. Isolated pregnancy-induced anti-thrombin deficiency in a woman with twin pregnancy.

    PubMed

    Kawabata, Kosuke; Morikawa, Mamoru; Yamada, Takahiro; Minakami, Hisanori

    2016-06-01

    A woman with twin pregnancy had a gradual decline in anti-thrombin (AT) activity from 72% at gestational week (GW) 29(-3/7) , to 53% at GW31(-2/7) , and to 41% at GW32(-2/7) , at which time hypertension (148/90 mmHg) and proteinuria (protein-to-creatinine ratio [P/Cr], 0.79 mg/mg) developed in the presence of normal platelet count (159 × 10(9) /L) and serum aspartate aminotransferase/lactate dehydrogenase (22/164 IU/L). AT product was given three times to maintain AT activity >50% and blood pressure was maintained below 155/95 mmHg with no treatment, but generalized edema with a weekly weight gain of 4.9 kg and increased proteinuria (to P/Cr, 7.6 mg/mg) required cesarean section at GW33(-3/7) . This case highlights the occurrence of pregnancy-induced AT deficiency alone in the absence of any other abnormality, including hypertension, proteinuria, or thrombocytopenia. Measurement of AT activity was considered helpful for determination of the appropriate time for delivery in this patient.

  4. Stat5-deficient hematopoiesis is permissive for Myc-induced B-cell leukemogenesis.

    PubMed

    Wang, Zhengqi; Medrzycki, Magdalena; Bunting, Silvia T; Bunting, Kevin D

    2015-10-06

    Despite being an attractive molecular target for both lymphoid and myeloid leukemias characterized by activated tyrosine kinases, the molecular and physiological consequences of reduced signal transducer and activator of transcription-5 (Stat5) during leukemogenesis are not well known. Stat5 is a critical regulator of mouse hematopoietic stem cell (HSC) self-renewal and is essential for normal lymphocyte development. We report that pan-hematopoietic deletion in viable adult Vav1-Cre conditional knockout mice as well as Stat5ab(null/null) fetal liver transplant chimeras generated HSCs with reduced expression of quiescence regulating genes (Tie2, Mpl, Slamf1, Spi1, Cited2) and increased expression of B-cell development genes (Satb1, Dntt, Btla, Flk2). Using a classical murine B-cell acute lymphoblastic leukemia (B-ALL) model, we demonstrate that these HSCs were also poised to produce a burst of B-cell precursors upon expression of Bcl-2 combined with oncogenic Myc. This strong selective advantage for leukemic transformation in the background of Stat5 deficient hematopoiesis was permissive for faster initiation of Myc-induced transformation to B-ALL. However, once established, the B-ALL progression in secondary transplant recipients was Stat5-independent. Overall, these studies suggest that Stat5 can play multiple important roles that not only preserve the HSC compartment but can limit accumulation of potential pre-leukemic lymphoid populations.

  5. Mice Deficient in CD38 Develop an Attenuated Form of Collagen Type II-Induced Arthritis

    PubMed Central

    Postigo, Jorge; Iglesias, Marcos; Cerezo-Wallis, Daniela; Rosal-Vela, Antonio; García-Rodríguez, Sonia; Zubiaur, Mercedes; Sancho, Jaime

    2012-01-01

    CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses. PMID:22438945

  6. 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.

  7. Anti-diabetic activity of recombinant irisin in STZ-induced insulin-deficient diabetic mice.

    PubMed

    Duan, Huikun; Ma, Baicheng; Ma, Xiaofeng; Wang, Haisong; Ni, Zaizhong; Wang, Bin; Li, Xiaodan; Jiang, Pingzhe; Umar, Muhammad; Li, Minggang

    2016-03-01

    In order to investigate the hypoglycemic effects and potential mechanism of recombinant irisin on diabetes, STZ-induced diabetic mice were established and treated with irisin. The results showed that daily water and food intake, and blood glucose significantly decreased after various concentrations of recombinant irisin treatment by intraperitoneal injection, of which 1.0 mg/kg was the optimal dose for lowering blood glucose. However, the body weight exhibited no significant difference during the treatment within groups, although the 0.9% NaCl treated group showed a trend of decreased body weight and the irisin treated groups showed a tendency of increasing weight. The oral glucose tolerance was improved, and serum insulin and circulating irisin content were significantly elevated in diabetic mice after 1.0 mg/kg irisin-injection treatment, compared to diabetic mice treated with 0.9% NaCl. 1.0 mg/kg irisin-injection also significantly increased the expression of energy and metabolism-related genes. In addition, oral administration of irisin lowered the blood glucose in diabetic mice. Our data suggested that irisin could lower blood glucose in insulin-deficient diabetic mice, to some extent, through irisin-mediated induction of energy and metabolic genes expression. These observations laid a foundation for the development of irisin-based therapy.

  8. Acid Sphingomyelinase Deficiency Prevents Diet-induced Hepatic Triacylglycerol Accumulation and Hyperglycemia in Mice*

    PubMed Central

    Deevska, Gergana M.; Rozenova, Krassimira A.; Giltiay, Natalia V.; Chambers, Melissa A.; White, James; Boyanovsky, Boris B.; Wei, Jia; Daugherty, Alan; Smart, Eric J.; Reid, Michael B.; Merrill, Alfred H.; Nikolova-Karakashian, Mariana

    2009-01-01

    Acid sphingomyelinase plays important roles in ceramide homeostasis, which has been proposed to be linked to insulin resistance. To test this association in vivo, acid sphingomyelinase deletion (asm–/–) was transferred to mice lacking the low density lipoprotein receptor (ldlr–/–), and then offsprings were placed on control or modified (enriched in saturated fat and cholesterol) diets for 10 weeks. The modified diet caused hypercholesterolemia in all genotypes; however, in contrast to asm+/+/ldlr–/–, the acid sphingomyelinase-deficient littermates did not display hepatic triacylglyceride accumulation, although sphingomyelin and other sphingolipids were substantially elevated, and the liver was enlarged. asm–/–/ldlr–/– mice on a modified diet did not accumulate body fat and were protected against diet-induced hyperglycemia and insulin resistance. Experiments with hepatocytes revealed that acid sphingomyelinase regulates the partitioning of the major fatty acid in the modified diet, palmitate, into two competitive and inversely related pools, triacylglycerides and sphingolipids, apparently via modulation of serine palmitoyltransferase, a rate-limiting enzyme in de novo sphingolipid synthesis. These studies provide evidence that acid sphingomyelinase activity plays an essential role in the regulation of glucose metabolism by regulating the hepatic accumulation of triacylglycerides and sphingolipids during consumption of a diet rich in saturated fats. PMID:19074137

  9. Compromised virus-induced gene silencing in RDR6-deficient plants.

    PubMed

    Vaistij, Fabián E; Jones, Louise

    2009-03-01

    RNA silencing in plants serves as a potent antiviral defense mechanism through the action of small interfering RNAs (siRNAs), which direct RNA degradation. siRNAs can be derived directly from the viral genome or via the action of host-encoded RNA-dependent RNA polymerases (RDRs). Plant genomes encode multiple RDRs, and it has been demonstrated that plants defective for RDR6 hyperaccumulate several classes of virus. In this study, we compared the effectiveness of virus-induced gene silencing (VIGS) and RNA-directed DNA methylation (RdDM) in wild-type and RDR6-deficient Nicotiana benthamiana plants. For the potexvirus Potato virus X (PVX) and the potyvirus Plum pox virus (PPV), the efficiency of both VIGS and RdDM were compromised in RDR6-defective plants despite accumulating high levels of viral siRNAs similar to infection of wild-type plants. The reduced efficiency of VIGS and RdDM was unrelated to the size class of siRNA produced and, at least for PVX, was not dependent on the presence of the virus-encoded silencing suppressor protein, 25K. We suggest that primary siRNAs produced from PVX and PPV in the absence of RDR6 may not be good effectors of silencing and that RDR6 is required to produce secondary siRNAs that drive a more effective antiviral response.

  10. Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma

    PubMed Central

    Binder Gallimidi, Adi; Nussbaum, Gabriel; Hermano, Esther; Weizman, Barak; Meirovitz, Amichay; Vlodavsky, Israel; Götte, Martin; Elkin, Michael

    2017-01-01

    Syndecan-1 (Sdc1) is an important member of the cell surface heparan sulfate proteoglycan family, highly expressed by epithelial cells in adult organisms. Sdc1 is involved in the regulation of cell migration, cell-cell and cell-matrix interactions, growth-factor, chemokine and integrin activity, and implicated in inflammatory responses and tumorigenesis. Gastrointestinal tract represents an important anatomic site where loss of Sdc1 expression was reported both in inflammation and malignancy. However, the biological significance of Sdc1 in chronic colitis-associated tumorigenesis has not been elucidated. To the best of our knowledge, this study is the first to test the effects of Sdc1 loss on colorectal tumor development in inflammation-driven colon tumorigenesis. Utilizing a mouse model of colitis-related colon carcinoma induced by the carcinogen azoxymethane (AOM), followed by the inflammatory agent dextran sodium sulfate (DSS), we found that Sdc1 deficiency results in increased susceptibility to colitis-associated tumorigenesis. Importantly, colitis-associated tumors developed in Sdc1-defficient mice were characterized by increased local production of IL-6, activation of STAT3, as well as induction of several STAT3 target genes that act as important effectors of colonic tumorigenesis. Altogether, our results highlight a previously unknown effect of Sdc1 loss in progression of inflammation-associated cancer and suggest that decreased levels of Sdc1 may serve as an indicator of colon carcinoma progression in the setting of chronic inflammation. PMID:28350804

  11. Pulmonary lesions induced by Pasteurella haemolytica in neutrophil sufficient and neutrophil deficient calves.

    PubMed Central

    Breider, M A; Walker, R D; Hopkins, F M; Schultz, T W; Bowersock, T L

    1988-01-01

    The role of neutrophils in the development of peracute lung lesions of bovine pneumonic pasteurellosis was investigated. Eight calves were divided into two groups of four calves each. Group I was treated with intravenous phosphate-buffered saline and served as the neutrophil sufficient calves. Group II was treated with intravenous hydroxyurea which produced a state of neutropenia. When peripheral blood neutrophil numbers dropped below 300 cells/microL in group II, all calves were challenged with an intrabronchial bolus of Pasteurella haemolytica in the log phase of growth. An acute inflammatory process occurred in both groups of calves indicated by a rise in body temperature. While pulmonary lesions occurred in both groups by six hours postinoculation, they varied in pathological characteristics. Pulmonary lesions in the neutrophil sufficient calves consisted of fibrinopurulent alveolitis-bronchiolitis with associated alveolar septal necrosis, interlobular edema, and intravascular thrombi. The neutrophil deficient calves had extensive intra-alveolar edema, interlobular edema, intraalveolar hemorrhage, atelectasis, and focal areas of alveolar septal necrosis. These results show that P. haemolytica can induce severe pulmonary tissue damage through both neutrophil dependent and neutrophil independent mechanisms. Images Fig. 1. Fig. 2. PMID:3370555

  12. 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.

  13. An Arabidopsis ABC Transporter Mediates Phosphate Deficiency-Induced Remodeling of Root Architecture by Modulating Iron Homeostasis in Roots.

    PubMed

    Dong, Jinsong; Piñeros, Miguel A; Li, Xiaoxuan; Yang, Haibing; Liu, Yu; Murphy, Angus S; Kochian, Leon V; Liu, Dong

    2017-02-13

    The remodeling of root architecture is a major developmental response of plants to phosphate (Pi) deficiency and is thought to enhance a plant's ability to forage for the available Pi in topsoil. The underlying mechanism controlling this response, however, is poorly understood. In this study, we identified an Arabidopsis mutant, hps10 (hypersensitive to Pi starvation 10), which is morphologically normal under Pi sufficient condition but shows increased inhibition of primary root growth and enhanced production of lateral roots under Pi deficiency. hps10 is a previously identified allele (als3-3) of the ALUMINUM SENSITIVE3 (ALS3) gene, which is involved in plant tolerance to aluminum toxicity. Our results show that ALS3 and its interacting protein AtSTAR1 form an ABC transporter complex in the tonoplast. This protein complex mediates a highly electrogenic transport in Xenopus oocytes. Under Pi deficiency, als3 accumulates higher levels of Fe(3+) in its roots than the wild type does. In Arabidopsis, LPR1 (LOW PHOSPHATE ROOT1) and LPR2 encode ferroxidases, which when mutated, reduce Fe(3+) accumulation in roots and cause root growth to be insensitive to Pi deficiency. Here, we provide compelling evidence showing that ALS3 cooperates with LPR1/2 to regulate Pi deficiency-induced remodeling of root architecture by modulating Fe homeostasis in roots.

  14. Ascorbate Alleviates Fe Deficiency-Induced Stress in Cotton (Gossypium hirsutum) by Modulating ABA Levels.

    PubMed

    Guo, Kai; Tu, Lili; Wang, Pengcheng; Du, Xueqiong; Ye, Shue; Luo, Ming; Zhang, Xianlong

    2016-01-01

    Fe deficiency causes significant losses to crop productivity and quality. To understand better the mechanisms of plant responses to Fe deficiency, we used an in vitro cotton ovule culture system. We found that Fe deficiency suppressed the development of ovules and fibers, and led to tissue browning. RNA-seq analysis showed that the myo-inositol and galacturonic acid pathways were activated and cytosolic APX (ascorbate peroxidase) was suppressed in Fe-deficient treated fibers, which increased ASC (ascorbate) concentrations to prevent tissue browning. Suppression of cytosolic APX by RNAi in cotton increased ASC contents and delayed tissue browning by maintaining ferric reduction activity under Fe-deficient conditions. Meanwhile, APX RNAi line also exhibited the activation of expression of iron-regulated transporter (IRT1) and ferric reductase-oxidase2 (FRO2) to adapt to Fe deficiency. Abscisic acid (ABA) levels were significantly decreased in Fe-deficient treated ovules and fibers, while the upregulated expression of ABA biosynthesis genes and suppression of ABA degradation genes in Fe-deficient ovules slowed down the decreased of ABA in cytosolic APX suppressed lines to delay the tissue browning. Moreover, the application of ABA in Fe-deficient medium suppressed the development of tissue browning and completely restored the ferric reduction activity. In addition, ABA 8'-hydroxylase gene (GhABAH1) overexpressed cotton has a decreased level of ABA and shows more sensitivity to Fe deficiency. Based on the results, we speculate that ASC could improve the tolerance to Fe deficiency through activating Fe uptake and maintaining ABA levels in cotton ovules and fibers, which in turn reduces symptom formation.

  15. Ascorbate Alleviates Fe Deficiency-Induced Stress in Cotton (Gossypium hirsutum) by Modulating ABA Levels

    PubMed Central

    Guo, Kai; Tu, Lili; Wang, Pengcheng; Du, Xueqiong; Ye, Shue; Luo, Ming; Zhang, Xianlong

    2017-01-01

    Fe deficiency causes significant losses to crop productivity and quality. To understand better the mechanisms of plant responses to Fe deficiency, we used an in vitro cotton ovule culture system. We found that Fe deficiency suppressed the development of ovules and fibers, and led to tissue browning. RNA-seq analysis showed that the myo-inositol and galacturonic acid pathways were activated and cytosolic APX (ascorbate peroxidase) was suppressed in Fe-deficient treated fibers, which increased ASC (ascorbate) concentrations to prevent tissue browning. Suppression of cytosolic APX by RNAi in cotton increased ASC contents and delayed tissue browning by maintaining ferric reduction activity under Fe-deficient conditions. Meanwhile, APX RNAi line also exhibited the activation of expression of iron-regulated transporter (IRT1) and ferric reductase–oxidase2 (FRO2) to adapt to Fe deficiency. Abscisic acid (ABA) levels were significantly decreased in Fe-deficient treated ovules and fibers, while the upregulated expression of ABA biosynthesis genes and suppression of ABA degradation genes in Fe-deficient ovules slowed down the decreased of ABA in cytosolic APX suppressed lines to delay the tissue browning. Moreover, the application of ABA in Fe-deficient medium suppressed the development of tissue browning and completely restored the ferric reduction activity. In addition, ABA 8′-hydroxylase gene (GhABAH1) overexpressed cotton has a decreased level of ABA and shows more sensitivity to Fe deficiency. Based on the results, we speculate that ASC could improve the tolerance to Fe deficiency through activating Fe uptake and maintaining ABA levels in cotton ovules and fibers, which in turn reduces symptom formation. PMID:28101095

  16. Echocardiographic evidence for myocardial failure induced by taurine deficiency in domestic cats.

    PubMed Central

    Novotny, M J; Hogan, P M; Flannigan, G

    1994-01-01

    Dietary taurine-deficiency is a cause of dilated cardiomyopathy (DCM) in cats. While the incidence of clinical cases of feline DCM has markedly decreased since the association between DCM and taurine-deficiency was first recognized, not all cats maintained on taurine-deficient diets develop DCM. The objective was to temporally evaluate left ventricular (LV) function using M-mode echocardiography in 23 cats maintained on a taurine-deficient diet; 20 time-matched, taurine-supplemented cats served as controls. The duration of feeding trials ranged from 6-15 months. No diminution of myocardial function was recorded in a small number of taurine-deficient cats whereas cardiac performance in some taurine-deficient cats diminished to levels characteristic of DCM. Of the taurine-deficient cats, 17 (74%) experienced a greater than 25% reduction in fractional shortening and 21 (91%) had a greater than 25% increase in LV end-systolic short-axis diameter. On average, LV end-systolic short-axis diameter increased by 70% and fractional shortening decreased by 37% in taurine-deficient cats. Mean velocity of circumferential fiber shortening was similarly reduced in taurine-deficient cats. The greatest rate of change in M-mode echocardiographic variables occurred during the first four months on the taurine-deficient diet. Dietary taurine deficiency leads to a spectrum of changes in myocardial function in domestic cats. While DCM is observed in some cats, decreased systolic pump function and increased LV end-systolic short-axis diameter are more consistent findings. PMID:8143255

  17. 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

  18. Abscisic acid-deficient sit tomato mutant responses to cadmium-induced stress.

    PubMed

    Pompeu, Georgia B; Vilhena, Milca B; Gratão, Priscila L; Carvalho, Rogério F; Rossi, Mônica L; Martinelli, Adriana P; Azevedo, Ricardo A

    2017-03-01

    There is a very effective cross-talk between signals triggered by reactive oxygen species and hormonal responses in plants, activating proteins/enzymes likely to be involved in stress tolerance. Abscisic acid (ABA) is known as a stress hormone that takes part in the integration of signals. This work aimed to characterize the biochemical response and ultrastructural changes induced by cadmium (Cd) in the Micro-Tom (MT) sitiens ABA-deficient mutant (sit) and its wild-type (MT) counterpart. MT and sit plants were grown over a 96-h period in the presence of Cd (0, 10, and 100 μM CdCl2). The overall results indicated increases in lipid peroxidation, hydrogen peroxide content and in the activities of the key antioxidant enzymes such as catalase, glutathione reductase, and ascorbate peroxidase in both genotypes. On the other hand, no alteration was observed in chlorophyll content, while the activity of another antioxidant enzyme, superoxide dismutase, remained constant or even decreased in the presence of Cd. Roots and shoots of the sit mutant and MT were analyzed by light and transmission electron microscopy in order to characterize the structural changes caused by the exposure to this metal. Cd caused a decrease in intercellular spaces in shoots and a decrease in cell size in roots of both genotypes. In leaves, Cd affected organelle shape and internal organization of the thylakoid membranes, whereas noticeable increase in the number of mitochondria and vacuoles in MT and sit roots were observed. These results add new information that should help unravel the relative importance of ABA in regulating the cell responses to stressful conditions induced by Cd apart from providing the first characterization of this mutant to oxidative stress.

  19. 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

  20. 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.

  1. High-fat diet induces leptin resistance in leptin-deficient mice.

    PubMed

    Koch, C E; Lowe, C; Pretz, D; Steger, J; Williams, L M; Tups, A

    2014-02-01

    The occurrence of type II diabetes is highly correlated with obesity, although the mechanisms linking the two conditions are incompletely understood. Leptin is a potent insulin sensitiser and, in leptin-deficient, insulin insensitive, Lep(ob/ob) mice, leptin improves glucose tolerance, indicating that leptin resistance may link obesity to insulin insensitivity. Leptin resistance occurs in response to a high-fat diet (HFD) and both hyperleptinaemia and inflammation have been proposed as causative mechanisms. Scrutinising the role of hyperleptinaemia in this process, central hyperleptinaemia in Lep(ob/ob) mice was induced by chronic i.c.v. infusion of leptin (4.2 μg/day) over 10 days. This treatment led to a dramatic decline in body weight and food intake, as well as an improvement in glucose tolerance. Transfer to HFD for 4 days markedly arrested the beneficial effects of leptin on these parameters. Because Lep(ob/ob) mice are exquisitely sensitive to leptin, the possibility that leptin could reverse HFD-induced glucose intolerance in these animals was investigated. HFD led to increased body weight and glucose intolerance compared to a low-fat diet (LFD). Older and heavier Lep(ob/ob) mice were used as body weight-matched controls. Mice in each group received either i.p. leptin (1.25 mg/kg) or vehicle, and glucose tolerance, food intake and the number of phosphorylated signal transducer and activator of transcription (pSTAT)3 immunoreactive cells in the arcuate nucleus (ARC) and ventromedial hypothalamus (VMH) were analysed. Leptin improved glucose tolerance (P = 0. 019) and reduced food intake in Lep(ob/ob) mice on LFD (P ≤ 0.001) but was ineffective in mice on HFD. Furthermore, when leptin was administered centrally, the glucose tolerance of Lep(ob/ob) mice on HFD was significantly impaired (P = 0.007). Although leptin induced the number of pSTAT3 immunoreactive cells in the ARC and VMH of Lep(ob/ob) mice on LFD, HFD was associated with elevated pSTAT3

  2. 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

  3. Simultaneous determination of bromine and iodine in milk powder for adult and infant nutrition by plasma based techniques after digestion using microwave-induced combustion

    NASA Astrophysics Data System (ADS)

    Picoloto, Rochele S.; Doneda, Morgana; Flores, Eder L. M.; Mesko, Marcia F.; Flores, Erico M. M.; Mello, Paola A.

    2015-05-01

    In this work, bromine and iodine determination in milk powder for adult and infant nutrition was performed by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES) after digestion by microwave-induced combustion (MIC). Contrarily to previous works using MIC, a higher sample mass was digested (700 mg). Water and ammonium hydroxide (10 to 100 mmol L- 1) were investigated as absorbing solutions and accurate results were achieved using a 25 mmol L- 1 NH4OH solution. Moreover, the high stability of analytes after digestion (up to 30 days) using this solution was observed. The accuracy of the proposed MIC method was evaluated using certified and reference materials of milk powder (NIST 1549 and NIST 8435). No statistical difference was observed between results obtained by MIC-ICP-MS and reference values. Results for samples were also compared with those obtained by ICP-OES and no statistical difference was observed. Microwave-assisted alkaline extraction (MW-AE) was also evaluated for milk powder using NH4OH and tetramethylammonium hydroxide solutions. Solutions obtained after digestion by MIC (whole milk powder) presented low carbon content in digests (< 25 mg L- 1) while solutions obtained after alkaline extraction presented up to 10,000 mg L- 1 of C. MIC method was preferable in view of the possibility of obtaining solutions with low carbon content even using a relatively high sample mass (up to 700 mg) avoiding additional dilution prior to ICP-MS analysis, thus allowing better detection limits. Limits of detection obtained by MIC-ICP-MS were 0.007 and 0.003 μg g- 1 for Br and I, respectively, while for MW-AE were 0.1 and 0.05 μg g- 1 respectively for Br and I. Among the main advantages of the proposed method are the use of diluted alkaline solutions that is in agreement with green analytical chemistry recommendations, the high stability of analytes in solution and the suitability of digests for

  4. Elevated Slit2 Activity Impairs VEGF-induced Angiogenesis and Tumor Neovascularization in EphA2-deficient Endothelium

    PubMed Central

    Youngblood, Victoria; Wang, Shan; Song, Wenqiang; Walter, Debra; Hwang, Yoonha; Chen, Jin; Brantley-Sieders, Dana M.

    2015-01-01

    Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited by tumors. Indeed, tumors upregulate pro-angiogenic molecules while simultaneously suppressing angiostatic pathways in order to recruit blood vessels for growth, survival, and metastatic spread. Understanding how cancers exploit pro- and anti-angiogenic signals is a key step in developing new, molecularly targeted anti-angiogenic therapies. While EphA2, a receptor tyrosine kinase (RTK), is required for vascular endothelial growth factor (VEGF)-induced angiogenesis, the mechanism through which these pathways intersect remains unclear. Slit2 expression is elevated in EphA2-deficient endothelium, and here it is reported that inhibiting Slit activity rescues VEGF-induced angiogenesis in cell culture and in vivo, as well as VEGF-dependent tumor angiogenesis, in EphA2-deficient endothelial cells and animals. Moreover, blocking Slit activity or Slit2 expression in EphA2-deficient endothelial cells restores VEGF-induced activation of Src and Rac, both of which are required for VEGF-mediated angiogenesis. These data suggest that EphA2 suppression of Slit2 expression and Slit angiostatic activity enables VEGF-induced angiogenesis in vitro and in vivo, providing a plausible mechanism for impaired endothelial responses to VEGF in the absence of EphA2 function. PMID:25504371

  5. ARYL HYDROCARBON RECEPTOR DEFICIENCY PROTECTS MICE FROM DIET-INDUCED ADIPOSITY AND METABOLIC DISORDERS THROUGH INCREASED ENERGY EXPENDITURE

    PubMed Central

    Zhang, Zhi-Ming; Jaeger, Cassie D.; Krager, Stacey L.; Bottum, Kathleen M.; Liu, Jianghua; Liao, Duan-Fang; Tischkau, Shelley A.

    2015-01-01

    BACKGROUND/OBJECTIVES Epidemics of obesity and diabetes are escalating. High-calorie/high-fat food is a major cause for these global health issues, but molecular mechanisms underlying high-fat, diet-induced obesity are still not well understood. The aryl hydrocarbon receptor (AhR), a transcription factor that acts as a xenobiotic sensor, mediates environmental toxicant-induced obesity, insulin resistance and development of diabetes. AhR also influences lipid metabolism and diet-induced obesity. The effects of AhR deficiency on diet-induced obesity, hepatic steatosis and insulin resistance were examined. METHODS : Male wild type (WT), AhR null (AhR−/−) and AhR heterozygote (AhR+/−) mice were fed a normal chow diet (NCD, 10% kcal from fat) or a high-fat diet (HFD, 60% kcal from fat) for up to 14 weeks. Adiposity, adipose and liver morphology, insulin signaling, metabolic parameters and gene profiles were assessed. RESULTS AhR deficiency protected against HFD-induced obesity, hepatic steatosis, insulin resistance and inflammation. Moreover, AhR deficiency preserved insulin signaling in major metabolic tissues. These protective effects result from a higher energy expenditure in AhR-deficient mice compared to WT. Levels of transcript for both the thermogenic gene, uncoupling protein 1 (Ucp1), in brown adipose tissue and mitochondrial β-oxidation genes in muscle were significantly higher in AhR−/− and AhR+/− mice compared to WT. CONCLUSIONS This work documents a physiologically relevant function for AhR in regulation of body weight, hepatic fat deposition, insulin sensitivity and energy expenditure under HFD exposure, suggesting that AhR signaling may be developed as a potential therapeutic target for treatment of obesity and metabolic disorders. PMID:25907315

  6. 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.

  7. Radionuclide Basics: Iodine

    MedlinePlus

    ... like particles and fall to the ground. from nuclear weapons or reactor accidents can occur in particle form, which can be ingested in food or water. I-131 is often used to treat ... used in nuclear medicine. External exposure to large amounts of iodine ...

  8. Biotin-deficient diet induces chromosome misalignment and spindle defects in mouse oocytes.

    PubMed

    Tsuji, Ai; Nakamura, Toshinobu; Shibata, Katsumi

    2015-01-01

    Increased abnormal oocytes due to meiotic chromosome misalignment and spindle defects lead to elevated rates of infertility, miscarriage, and trisomic conceptions. Here, we investigated the effect of biotin deficiency on oocyte quality. Three-week-old female ICR mice were fed a biotin-deficient or control diet (0, 0.004 g biotin/kg diet) for 21 days. On day 22, these mouse oocytes were analyzed by immunofluorescence. Due to biotin, undernutrition increased the frequency of abnormal oocytes (the biotin deficient vs. control: 40 vs. 16%). Next, the remaining mice in the biotin-deficient group were fed a control or biotin-deficient diet from day 22 to 42. Although biotin nutritional status in the recovery group was restored, the frequency of abnormal oocytes in the recovery group was still higher than that in the control group (48 vs. 18%). Our results indicate that steady, sufficient biotin intake is required for the production of high-quality oocytes in mice.

  9. Food Group Intakes as Determinants of Iodine Status among US Adult Population

    PubMed Central

    Lee, Kyung Won; Shin, Dayeon; Cho, Mi Sook; Song, Won O.

    2016-01-01

    Adequate intake of iodine is essential for proper thyroid function. Although dietary reference intakes for iodine have been established, iodine intake cannot be estimated due to the lack of data on iodine contents in foods. We aimed to determine if food group intakes can predict iodine status assessed by urinary iodine concentration (UIC) from spot urine samples of 5967 US adults in the National Health and Nutrition Examination Survey (NHANES) 2007–2012. From an in-person 24-h dietary recall, all foods consumed were aggregated into 12 main food groups using the individual food code of the US Department of Agriculture (USDA); dairy products, meat/poultry, fish/seaweed, eggs, legumes/nuts/seeds, breads, other grain products, fruits, vegetables, fats/oils, sugars/sweets, and beverages. Chi-square test, Spearman correlation, and multiple linear regression analyses were conducted to investigate the predictability of food group intakes in iodine status assessed by UIC. From the multiple linear regressions, the consumption of dairy products, eggs, and breads, and iodine-containing supplement use were positively associated with UIC, whereas beverage consumption was negatively associated with UIC. Among various food group intakes, dairy product intake was the most important determinant of iodine status in both US men and women. Subpopulation groups with a high risk of iodine deficiency may need nutritional education regarding the consumption of dairy products, eggs, and breads to maintain an adequate iodine status. Efforts toward a better understanding of iodine content in each food and a continued monitoring of iodine status within US adults are both warranted. PMID:27240399

  10. Food Group Intakes as Determinants of Iodine Status among US Adult Population.

    PubMed

    Lee, Kyung Won; Shin, Dayeon; Cho, Mi Sook; Song, Won O

    2016-05-26

    Adequate intake of iodine is essential for proper thyroid function. Although dietary reference intakes for iodine have been established, iodine intake cannot be estimated due to the lack of data on iodine contents in foods. We aimed to determine if food group intakes can predict iodine status assessed by urinary iodine concentration (UIC) from spot urine samples of 5967 US adults in the National Health and Nutrition Examination Survey (NHANES) 2007-2012. From an in-person 24-h dietary recall, all foods consumed were aggregated into 12 main food groups using the individual food code of the US Department of Agriculture (USDA); dairy products, meat/poultry, fish/seaweed, eggs, legumes/nuts/seeds, breads, other grain products, fruits, vegetables, fats/oils, sugars/sweets, and beverages. Chi-square test, Spearman correlation, and multiple linear regression analyses were conducted to investigate the predictability of food group intakes in iodine status assessed by UIC. From the multiple linear regressions, the consumption of dairy products, eggs, and breads, and iodine-containing supplement use were positively associated with UIC, whereas beverage consumption was negatively associated with UIC. Among various food group intakes, dairy product intake was the most important determinant of iodine status in both US men and women. Subpopulation groups with a high risk of iodine deficiency may need nutritional education regarding the consumption of dairy products, eggs, and breads to maintain an adequate iodine status. Efforts toward a better understanding of iodine content in each food and a continued monitoring of iodine status within US adults are both warranted.

  11. Spatial variability of drinking water iodine in Denmark: implications for future policy making

    NASA Astrophysics Data System (ADS)

    Voutchkova, Denitza; Ernstsen, Vibeke; Kristiansen, Søren; Hansen, Birgitte

    2014-05-01

    The iodine-an essential component of human thyroid hormones-is provided to our organisms naturally from the food and water and/or is added artificially to the diet. One of the major natural contributors to the dietary iodine intake in Denmark is the drinking water. Both insufficient or excessive iodine intake can cause health problems however the attention falls mainly on the iodine deficiency (ID). Denmark is classified to have mild ID, which is based on sub-national data only. On a bigger scale, in Europe, about 40% of the general population is estimated to suffer from insufficient iodine intake (based on recent update on the iodine status worldwide). A mandatory addition of iodine to the salt was introduced in 2001 in Denmark to address the population's mild deficiency. One of the components of the Danish monitoring program investigating the effect of the salt iodizing (DanThyr) was based on the geographical variation of drinking water iodine levels. More specifically, the location of the two DanThyr cohort studies was chosen to reflect the low concentrations in the western part of Denmark and higher concentration in the eastern part. However, the knowledge about the spatial variability of iodine in Danish ground- and drinking water at that time was quite limited and misrepresentation of the natural variability is suspected. The presented sampling campaign was completed in 2013, and includes 144 waterworks with annual abstraction of about 175 mio m3 groundwater (~45% of the total groundwater abstraction by all active public and private Danish waterworks). The results show a surprisingly complex spatial pattern concerning both the iodine concentrations and speciation. By estimating the dietary iodine intake from water and comparing it to the WHO recommendations, it becomes possible to recognize potentially deficient/excessive geographical areas. Moreover, it is demonstrated that drinking water iodine levels (major dietary iodine contributor in Denmark) can be

  12. Influence of nutritional state on the disposal of orally and intramuscularly administered iodized oil to iodine repleted older children and adult women.

    PubMed

    Fierro-Benitez, R; Sandoval-Valencia, H; Sevilla-Munoz, B; Rodriguez, E; Gualotuna, E; Fierro-Carrion, G; Pacheco-Bastides, V; Andrade, J; Wang, P H; Stanbury, J B

    1989-06-01

    Iodinated oil (Ethiodol, 1 or 2 ml) was administered po or by im administration to adult women and older children in rural highland Ecuador who were either well nourished or malnourished to determine the effect of nutritional status on the disposal rate of iodine. These subjects resides in a region previously severely deficient in iodine, but this had been corrected in these subjects by prior administration of iodinated oil or by use of iodized salt or both. Malnutrition as determined by the conventional standards of height for age was associated with a significantly shortened retention time of the administered iodine, whether given po or im. The half life of retention was approximately half in the malourished of that in the well nourished. If these findings can be extrapolated to chronically iodine deficient subjects, then malnourished populations in need of iodine supplementation should either receive higher dosages than those conventionally employed or more frequent dosage.

  13. 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

  14. 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.

  15. Soluble Epoxide Hydrolase Deficiency Inhibits Dextran Sulfate Sodium-induced Colitis and Carcinogenesis in Mice

    PubMed Central

    DONG, HUA; LIAO, JIE; HAMMOCK, BRUCE D.; YANG, GUANG-YU

    2014-01-01

    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 mm3 vs. 22.42±11.22 mm3), 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

  16. Group IVA phospholipase A(2) deficiency prevents CCl4-induced hepatic cell death through the enhancement of autophagy.

    PubMed

    Ishihara, Keiichi; Kanai, Shiho; Tanaka, Kikuko; Kawashita, Eri; Akiba, Satoshi

    2016-02-26

    Group IVA phospholipase A2 (IVA-PLA2), which generates arachidonate, plays a role in inflammation. IVA-PLA2-deficiency reduced hepatotoxicity and hepatocyte cell death in mice that received a single dose of carbon tetrachloride (CCl4) without any inhibitory effects on CCl4-induced lipid peroxidation. An immunoblot analysis of extracts from wild-type mouse- and IVA-PLA2 KO mouse-derived primary hepatocytes that transiently expressed microtubule-associated protein 1 light chain 3B (LC3) revealed a higher amount of LC3-II, a typical index of autophagosome formation, in IVA-PLA2-deficient cells, suggesting the enhancement of constitutive autophagy. IVA-PLA2 may promote CCl4-induced cell death through the suppression of constitutive autophagy in hepatocytes.

  17. Iodine source apportionment in the Malawian diet

    PubMed Central

    Watts, M. J.; Joy, E. J. M.; Young, S. D.; Broadley, M. R.; Chilimba, A. D. C.; Gibson, R. S.; Siyame, E. W. P.; Kalimbira, A. A.; Chilima, B.; Ander, E. L.

    2015-01-01

    The aim of this study was to characterise nutritional-I status in Malawi. Dietary-I intakes were assessed using new datasets of crop, fish, salt and water-I concentrations, while I status was assessed for 60 women living on each of calcareous and non-calcareous soils as defined by urinary iodine concentration (UIC). Iodine concentration in staple foods was low, with median concentrations of 0.01 mg kg−1 in maize grain, 0.008 mg kg−1 in roots and tubers, but 0.155 mg kg−1 in leafy vegetables. Freshwater fish is a good source of dietary-I with a median concentration of 0.51 mg kg−1. Mean Malawian dietary-Iodine intake from food, excluding salt, was just 7.8 μg d−1 compared to an adult requirement of 150 μg d−1. Despite low dietary-I intake from food, median UICs were 203 μg L−1 with only 12% defined as I deficient whilst 21% exhibited excessive I intake. Iodised salt is likely to be the main source of dietary I intake in Malawi; thus, I nutrition mainly depends on the usage and concentration of I in iodised salt. Drinking water could be a significant source of I in some areas, providing up to 108 μg d−1 based on consumption of 2 L d−1. PMID:26503697

  18. Iodine source apportionment in the Malawian diet

    NASA Astrophysics Data System (ADS)

    Watts, M. J.; Joy, E. J. M.; Young, S. D.; Broadley, M. R.; Chilimba, A. D. C.; Gibson, R. S.; Siyame, E. W. P.; Kalimbira, A. A.; Chilima, B.; Ander, E. L.

    2015-10-01

    The aim of this study was to characterise nutritional-I status in Malawi. Dietary-I intakes were assessed using new datasets of crop, fish, salt and water-I concentrations, while I status was assessed for 60 women living on each of calcareous and non-calcareous soils as defined by urinary iodine concentration (UIC). Iodine concentration in staple foods was low, with median concentrations of 0.01 mg kg-1 in maize grain, 0.008 mg kg-1 in roots and tubers, but 0.155 mg kg-1 in leafy vegetables. Freshwater fish is a good source of dietary-I with a median concentration of 0.51 mg kg-1. Mean Malawian dietary-Iodine intake from food, excluding salt, was just 7.8 μg d-1 compared to an adult requirement of 150 μg d-1. Despite low dietary-I intake from food, median UICs were 203 μg L-1 with only 12% defined as I deficient whilst 21% exhibited excessive I intake. Iodised salt is likely to be the main source of dietary I intake in Malawi; thus, I nutrition mainly depends on the usage and concentration of I in iodised salt. Drinking water could be a significant source of I in some areas, providing up to 108 μg d-1 based on consumption of 2 L d-1.

  19. The influence of iodine on the immunological properties of thyroglobulin and its immunological complexes.

    PubMed

    Gardas, A

    1991-01-01

    Several papers described different immunological properties of thyroglobulin (Tg) after iodination. The influence of iodine-iodide solution on the immunological properties of hTg and its immunological complexes with autoantibodies (aAbs) were studied. Human Tg coated to polystyrene plates, incubated for 30 min with iodine-iodide solution at concentration from 1 to 200 microM at pH 9.0 lost its ability to bind aAbs. Preincubation with iodine (2 microM), decreased aAbs binding by 50%. Tg epitope inactivation induced by iodine depended on the buffer pH and the presence of carbonate ions. The binding of rabbit Tg-antibodies to iodine pretreated Tg was only slightly changed. Thyroglobulin preincubation with iodine solutions decreased aAbs binding from all tested sera (67) of patients with autoimmune thyroid disease (AITD). Excess of iodide (0.2 M KJ) or equimolar concentration of diiodotyrosine protects the Tg molecule from iodine induced inactivation. Immunological complexes of Tg with aAbs dissociate at low iodine concentrations. The results suggest that a product of iodine disproportionation reaction induces changes in the Tg molecule and Tg-aAb's complexes leading to complex dissociation or epitope inactivation.

  20. Iodine Status of New Zealand Elderly Residents in Long-Term Residential Care

    PubMed Central

    Miller, Jody C.; MacDonell, Sue O.; Gray, Andrew R.; Reid, Malcolm R.; Barr, David J.; Thomson, Christine D.; Houghton, Lisa A.

    2016-01-01

    In response to the re-emergence of iodine deficiency in New Zealand, in 2009 the government mandated that all commercially made breads be fortified with iodized salt. There has been no evaluation of the impact of the program on iodine status of the elderly, despite this population group being vulnerable to iodine deficiency or excess. The aim of this study was to describe the iodine status of elderly New Zealanders in residential aged-care homes following the implementation of the bread fortification program. A cross-sectional survey was conducted, involving 309 residents (median age 85 years) from 16 aged-care homes throughout NZ. Information on socio-demographic, anthropometric, dietary and health characteristics were collected. Casual spot urine samples were analysed for urinary iodine concentration (UIC). Blood samples were analysed for serum thyroglobulin, thyroglobulin antibodies, and other biochemical indices. The median UIC (MUIC) of the residents was 72 μg/L, indicating mild iodine deficiency, and 29% had a UIC < 50 μg/L. Median thyroglobulin concentration was 18 ng/mL and 26% had elevated thyroglobulin concentration (>40 ng/mL), suggesting iodine insufficiency. Diuretic use was associated with lower MUIC (p = 0.043). Synthetic thyroxine use was associated with lower odds of having a UIC < 50 μg/L (OR 0.32, p = 0.030)) and lower median thyroglobulin (−15.2 ng/mL, p = 0.001), compared with untreated participants. Frailty was associated with elevated thyroglobulin (p = 0.029), whereas anemia was associated with lower thyroglobulin (p = 0.016). Iodine insufficiency persists in New Zealanders residing in residential aged-care homes despite increasing iodine intake from fortified bread. Research is required to establish optimal iodine intake and status in the elderly. PMID:27455319

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