Neonatal pyruvate dehydrogenase deficiency due to a R302H mutation in the PDHA1 gene: MRI findings

International Nuclear Information System (INIS)

Soares-Fernandes, Joao P.; Ribeiro, Manuel; Magalhaes, Zita; Rocha, Jaime F.; Teixeira-Gomes, Roseli; Cruz, Romeu; Leijser, Lara M.

2008-01-01

Pyruvate dehydrogenase (PDH) deficiency is one of the most common causes of congenital lactic acidosis. Correlations between the genetic defect and neuroimaging findings are lacking. We present conventional and diffusion-weighted MRI findings in a 7-day-old male neonate with PDH deficiency due to a mosaicism for the R302H mutation in the PDHA1 gene. Corpus callosum dysgenesis, widespread increased diffusion in the white matter, and bilateral subependymal cysts were the main features. Although confirmation of PDH deficiency depends on specialized biochemical analyses, neonatal MRI plays a role in evaluating the pattern and extent of brain damage, and potentially in early diagnosis and clinical decision making. (orig.)

Role of carglumic acid in the treatment of acute hyperammonemia due to N-acetylglutamate synthase deficiency

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Häberle J

2011-08-01

Full Text Available Johannes HäberleKinderspital Zürich, Abteilung Stoffwechsel, Zürich, SwitzerlandAbstract: N-acetylglutamate synthase (NAGS deficiency is a rare inborn error of metabolism affecting ammonia detoxification in the urea cycle. The product of NAGS is N-acetylglutamate which is the absolutely required allosteric activator of the first urea cycle enzyme carbamoylphosphate synthetase 1. In defects of NAGS, the urea cycle function can be severely affected resulting in fatal hyperammonemia in neonatal patients or at any later stage in life. NAGS deficiency can be treated with a structural analog of N-acetylglutamate, N-carbamyl-L-glutamate, which is available for enteral use as a licensed drug. Since NAGS deficiency is an extremely rare disorder, reports on the use of N-carbamyl-L-glutamate are mainly based on single patients. According to these, the drug is very effective in treating acute hyperammonemia by avoiding the need for detoxification during the acute metabolic decompensation. Also during long-term treatment, N-carbamyl-L-glutamate is effective in maintaining normal plasma ammonia levels and avoiding the need for additional drug therapy or protein-restricted diet. Open questions remain which concern the optimal dosage in acute and long-term use of N-carbamyl-L-glutamate and potential additional disorders in which the drug might also be effective in treating acute hyperammonemia. This review focuses on the role of N-carbamyl-L-glutamate for the treatment of acute hyperammonemia due to primary NAGS deficiency but will briefly discuss the current knowledge on the role of N-carbamyl-L-glutamate for treatment of secondary NAGS deficiencies.Keywords: carglumic acid, carbamylglutamate, N-carbamyl-L-glutamate, N-acetylglutamate synthase deficiency, NAGS deficiency, hyperammonemia

Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice.

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Somm, Emmanuel; Guérardel, Audrey; Maouche, Kamel; Toulotte, Audrey; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Françoise; Maskos, Uwe; Hüppi, Petra S; Schwitzgebel, Valérie M

2014-05-01

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and β2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7β2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7β2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7β2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7β2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central β2nAChR deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Venous thromboembolism associated with protein S deficiency due ...

Indian Academy of Sciences (India)

EWA WYPASEK

2017-12-11

Dec 11, 2017 ... qualitative tests, PS deficiency is classified as type I (low- ... fied studies of genotype–phenotype correlation and search. 1047 .... assay (Berichrom Protein C, Siemens Healthcare Diagnos- ..... tional international cohort study.

Gender role across development in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

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Long, Dominique N; Wisniewski, Amy B; Migeon, Claude J

2004-10-01

This study evaluated the degree of femininity and masculinity at different developmental stages in a group of adult women, some of whom were exposed to elevated prenatal adrenal androgens as a result of congenital adrenal hyperplasia (CAH) due to 21 hydroxylase (21-OH) deficiency. Women who had presented to the Johns Hopkins Hospital Pediatric Endocrine Clinic for treatment of CAH due to 21-OH deficiency were included. The control group consisted of sisters of CAH participants and women referred for evaluation of polycystic ovary syndrome. Study participants were given a questionnaire asking them to indicate their degree of masculinity and femininity during childhood, adolescence, and adulthood. In addition, participants were asked questions related to their play behavior during childhood, including playmate preferences, toy preferences, and admiration of male or female characters during fantasy play. Across participant groups, self-reported femininity decreased in a dose response manner, according to prenatal androgen exposure. For all groups, femininity increased through developmental stages. Women with salt-losing CAH remained less feminine than controls into adulthood. Conversely, self-reported masculinity increased in a dose-response manner, according to prenatal androgen exposure, across participant groups. Women with CAH showed a decrease in masculinity across developmental stages, such that by adulthood, there were no significant differences in masculinity between controls and the women with CAH. Women with salt-losing CAH were more likely to recall preferences for boy playmates, male-typical toys, and admiration for male characters during childhood than other study participants. Our data support the effect of both prenatal androgen exposure and socialization on gender role behavior in adult women with CAH due to 21-OH deficiency.

Ehlers Danlos syndrome, kyphoscoliotic type due to Lysyl Hydroxylase 1 deficiency in two children without congenital or early onset kyphoscoliosis

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van Dijk, Fleur S.; Mancini, Grazia M. S.; Maugeri, Alessandra; Cobben, Jan M.

2017-01-01

We report two children with Ehlers Danlos, kyphoscoliotic type confirmed by Lysyl Hydroxylase 1 deficiency due to bi-allelic PLOD1 mutations (kEDS-PLOD1) who were initially thought to have either a diagnosis of classical EDS (cEDS) or a neuromuscular disorder due to absence of (congenital)

Iodine Deficiency

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Zimmermann, M.B.

2009-01-01

Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected.

A prospective study of etiology of primary Amenorrhea with especial evaluation for non classic congenital adrenal hyperplasia due to 21 Hydroxylase deficiency

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Moayeri H

2002-07-01

Full Text Available Amenorrhea, an absence of menses is a symptom that generally brings teenagers for evaluation. This study was undertaken to determine the etiology of primary amenorrhea with especial concern to non classic congential adrenal hyperplasia (NC-CAH-due 21 hydroxylase deficiency among female adolescents refered to clinics of Pediatric Endocrinology of Tehran and Iran University of Medical sciences and private office. One hundred and five female adolescents were studied. All patients were examined by pediatric endocrinologist.Routine lab tests, FSH, LH, prolactin, T4, TSH, 17-hydroxyprogesterone and in some cases ACTH Stimulation test for screening of NC-CAH due to 21 OH deficiency were performed. Chromosmal analysis, sonography of the ovaries and CT scan or MRI of the brain was performed in some of them. Forty-three patients (41% had ypergonaldotropic hypogonadism and sixty two patiens (59% ahd hypogonadotropic hypogonadism. Turner’s syndrome and constitutional delay of puberty were the most common causes of primary amenorrhea in our study. The frequency of primary amenorrhea in our study. The frequency of primary amenorrhea due to 21-OH deficient NC-CAH was 6.6% in overall (105 cases. This study shows that in a population with high incidence of consanguineous marriages, some rare genetic disorders such as 21 OH deficient NC-CAH are relatively common

Lactate disposal via gluconeogenesis is increased during exercise in patients with mitochondrial myopathy due to complex I deficiency

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Roef, MJ; Kalhan, SC; Reijngoud, DJ; De Meer, K; Berger, Ruud

This study evaluated lactate disposal via gluconeogenesis as well as effects of FFA availability on gluconeogenesis via pyruvate (GNG(PYR)) in patients with mitochondrial myopathy due to complex I deficiency (CID). The rates of GNG(PYR) were measured in three CID patients and six healthy controls at

Isolated angioedema of the bowel due to C1 esterase inhibitor deficiency: a case report and review of literature

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Kothari Shivangi T

2011-02-01

Full Text Available Abstract Introduction We report a rare, classic case of isolated angioedema of the bowel due to C1-esterase inhibitor deficiency. It is a rare presentation and very few cases have been reported worldwide. Angioedema has been classified into three categories. Case presentation A 66-year-old Caucasian man presented with a ten-month history of episodic severe cramping abdominal pain, associated with loose stools. A colonoscopy performed during an acute attack revealed nonspecific colitis. Computed tomography of the abdomen performed at the same time showed a thickened small bowel and ascending colon with a moderate amount of free fluid in the abdomen. Levels of C4 ( Conclusion In addition to a detailed comprehensive medical history, laboratory data and imaging studies are required to confirm a diagnosis of angioedema due to C1 esterase inhibitor deficiency.

Management of chronic lateral instability due to lateral collateral ligament deficiency after total knee arthroplasty: a case report

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Petersilge William J

2010-05-01

Full Text Available Abstract Introduction Lateral instability following total knee arthroplasty (TKA is a rare condition with limited report of treatment options. The objective of this case presentation is to demonstrate the outcomes of different surgical procedures performed in a single patient with lateral collateral ligament (LCL deficiency. Case presentation We present a case of chronic lateral instability due to LCL deficiency after primary TKA in a 47-year-old Caucasian woman with an obesity problem. Multiple treatment options have been performed in order to manage this problem, including the following: ligament reconstruction; combined ligament reconstruction and constrained implant; and rotating-hinge knee prosthesis that was the most recent surgery. All ligament reconstruction procedures failed within one year. The varus-valgus constrained prosthesis provided stability for six years. Conclusions Ligament reconstruction alone cannot provide enough stability for the treatment of chronic lateral instability in patients with obesity problems and LCL deficiency. When the reconstruction fails, a salvage procedure with rotating-hinge knee is still available.

Effects of protein-deficient nutrition during rat pregnancy and development on developmental hindlimb crossing due to methylmercury intoxication

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Chakrabarti, S.K.; Bai, Chengjiang [Montreal Univ., Quebec (Canada). Dept. de Medecine du Travail et Hygiene du Milieu

2000-07-01

Pregnant rats were fed either a control (20% protein) or low (3.5%) protein diet during gestation and lactation. The pups were separated from their mothers on postnatal day 21, and were given the same dient as their corresponding mothers. The groups of pups from each diet group were treated on either postnatal day 21 or postnatal day 60 with 7.5 mg methylmercury chloride (MeHgCl) per kg b.w. once daily by gavage for 10 consecutive days, and the development of ataxia (hind-limb corossing) was monitored. The offspring from mothers on the protein-deficient diet were found to be more sensitive to MeHg-induced ataxia than those on the protein-sufficient diet. The former accumulated more mercury in different brain regions than the latter. The rates of protein synthesis in different brain regions of the offspring fed the protein-deficient diet were significantly reduced compared with the rates in those fed the protein-sufficient diet. However, MeHg treatment did not significantly modify the rates of such protein synthesis further in protein-deficient rats. Thus, a significantly much higher inhibition of the intrinsic rates of protein synthesis in different brain regions due to severe protein deficiency, as observed in this study, may be partly responsible for the increased susceptibility of developing rats fed a protein-deficient diet to MeHg-induced ataxia, or hindlimb crossing, although other factor(s) might also be involved. (orig.)

Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report

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Tufan Ali

2012-06-01

Full Text Available Abstract Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were “irritability, regressive behavior, apathy, crying and truancy” which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg’s sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg’s sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features

Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency.

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Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

2004-03-01

A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency

OpenAIRE

Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

2004-01-01

A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

Refractory Abdominal Pain in a Patient with Chronic Lymphocytic Leukemia: Be Wary of Acquired Angioedema due to C1 Esterase Inhibitor Deficiency

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Abdullateef Abdulkareem

2018-01-01

Full Text Available Acquired angioedema due to C1 inhibitor deficiency (C1INH-AAE is a rare and potentially fatal syndrome of bradykinin-mediated angioedema characterized by episodes of angioedema without urticaria. It typically manifests with nonpitting edema of the skin and edema in the gastrointestinal (GI tract mucosa or upper airway. Edema of the upper airway and tongue may lead to life-threatening asphyxiation. C1INH-AAE is typically under-diagnosed because of its rarity and its propensity to mimic more common abdominal conditions and allergic reactions. In this article, we present the case of a 62-year-old male with a history of recently diagnosed chronic lymphocytic leukemia (CLL who presented to our hospital with recurrent abdominal pain, initially suspected to have Clostridium difficile colitis and diverticulitis. He received a final diagnosis of acquired angioedema due to C1 esterase inhibitor deficiency due to concomitant symptoms of lip swelling, cutaneous nonpitting edema of his lower extremities, and complement level deficiencies. He received acute treatment with C1 esterase replacement and icatibant and was maintained on C1 esterase infusions. He also underwent chemotherapy for his underlying CLL and did not experience further recurrence of his angioedema.

Unexpected ethical dilemmas in sex assignment in 46,XY DSD due to 5-alpha reductase type 2 deficiency.

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Byers, Heather M; Mohnach, Lauren H; Fechner, Patricia Y; Chen, Ming; Thomas, Inas H; Ramsdell, Linda A; Shnorhavorian, Margarett; McCauley, Elizabeth A; Amies Oelschlager, Anne-Marie E; Park, John M; Sandberg, David E; Adam, Margaret P; Keegan, Catherine E

2017-06-01

Sex assignment at birth remains one of the most clinically challenging and controversial topics in 46,XY disorders of sexual development (DSD). This is particularly challenging in deficiency of 5-alpha reductase type 2 given that external genitalia are typically undervirilized at birth but typically virilize at puberty to a variable degree. Historically, most individuals with 5-alpha reductase deficiency were raised females. However, reports that over half of patients who underwent a virilizing puberty adopted an adult male gender identity have challenged this practice. Consensus guidelines on assignment of sex of rearing at birth are equivocal or favor male assignment in the most virilized cases. While a male sex of rearing assignment may avoid lifelong hormonal therapy and/or allow the potential for fertility, female sex assignment may be more consistent with external anatomy in the most severely undervirilized cases. Herein, we describe five patients with 46,XY DSD due 5-alpha-reductase type 2 deficiency, all with a severe phenotype. An inter-disciplinary DSD medical team at one of two academic centers evaluated each patient. This case series illustrates the complicated decision-making process of assignment of sex of rearing at birth in 5-alpha reductase type 2 deficiency and the challenges that arise when the interests of the child, parental wishes, recommendations of the medical team, and state law collide. © 2017 Wiley Periodicals, Inc.

Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

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Ramsay, D A; Drachman, D B; Drachman, R J; Stanley, E F

1992-05-29

The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

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Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Growth retardation due to idiopathic growth hormone deficiencies: MR findings in 24 patients

International Nuclear Information System (INIS)

Ochi, M.; Morikawa, M.; Yoshimoto, M.; Kinoshita, E.; Hayashi, K.

1992-01-01

In this study we evaluated the pituitary-hypothalamic abnormalities of ''idiopathic growth hormone (GH) deficiency'' as demonstrated by MR imaging. Twenty-four patients were examined with a 1.5-T unit using spin echo T-1 weighted images. The patients were divided into two groups according to MR findings: those with ectopic posterior pituitary glands (12 patients), and those with normal posterior pituitary glands (12 patients). Ten patients in the former group and four in the latter group had small anterior pituitary glands. All patients in the former group but only four in the latter group had severe GH deficiencies. Multiple hormone deficiencies were found in eight patients in the former group, but in only two in the latter group. It is speculated that perinatal abnormalities can cause posterior pituitary ectopia and that there is a close correlation between breech delivery and the male disadvantage of posterior pituitary ectopia. Half of our patients with ''idiopathic GH deficiency'' had ectopic posterior pituitaries. GH deficiency with posterior pituitary ectopia should no longer be considered idiopathic because organic lesions can now be identified during life. (orig./GD)

Early childhood BMI trajectories in monogenic obesity due to leptin, leptin receptor, and melanocortin 4 receptor deficiency.

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Kohlsdorf, Katja; Nunziata, Adriana; Funcke, Jan-Bernd; Brandt, Stephanie; von Schnurbein, Julia; Vollbach, Heike; Lennerz, Belinda; Fritsch, Maria; Greber-Platzer, Susanne; Fröhlich-Reiterer, Elke; Luedeke, Manuel; Borck, Guntram; Debatin, Klaus-Michael; Fischer-Posovszky, Pamela; Wabitsch, Martin

2018-02-27

To evaluate whether early childhood body mass index (BMI) is an appropriate indicator for monogenic obesity. A cohort of n = 21 children living in Germany or Austria with monogenic obesity due to congenital leptin deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed. A control group (CTRL) was defined that consisted of n = 22 obese adolescents with no mutation in the above mentioned genes. Early childhood (0-5 years) BMI trajectories were compared between the groups at selected time points. The LEP and LEPR group showed a tremendous increase in BMI during the first 2 years of life with all patients displaying a BMI >27 kg/m 2 (27.2-38.4 kg/m 2 ) and %BMI P95 (percentage of the 95th percentile BMI for age and sex) >140% (144.8-198.6%) at the age of 2 years and a BMI > 33 kg/m 2 (33.3-45.9 kg/m 2 ) and %BMI P95  > 184% (184.1-212.6%) at the age of 5 years. The MC4R and CTRL groups had a later onset of obesity with significantly lower BMI values at both time points (p BMI trajectories in this pediatric cohort with monogenic obesity we suggest that BMI values >27.0 kg/m 2 or %BMI P95  > 140% at the age of 2 years and BMI values >33.0 kg/m 2 or %BMI P95  > 184% at the age of 5 years may be useful cut points to identify children who should undergo genetic screening for monogenic obesity due to functionally relevant mutations in the leptin gene or leptin receptor gene.

Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency

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Peter J. McGuire

2014-02-01

Full Text Available The urea cycle functions to incorporate ammonia, generated by normal metabolism, into urea. Urea cycle disorders (UCDs are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA. A prospective analysis of interim HA events in a cohort of individuals with ornithine transcarbamylase (OTC deficiency, the most common UCD, revealed that intercurrent infection was the most common precipitant of acute HA and was associated with markers of increased morbidity when compared with other precipitants. To further understand these clinical observations, we developed a model system of metabolic decompensation with HA triggered by viral infection (PR8 influenza using spf-ash mice, a model of OTC deficiency. Both wild-type (WT and spf-ash mice displayed similar cytokine profiles and lung viral titers in response to PR8 influenza infection. During infection, spf-ash mice displayed an increase in liver transaminases, suggesting a hepatic sensitivity to the inflammatory response and an altered hepatic immune response. Despite having no visible pathological changes by histology, WT and spf-ash mice had reduced CPS1 and OTC enzyme activities, and, unlike WT, spf-ash mice failed to increase ureagenesis. Depression of urea cycle function was seen in liver amino acid analysis, with reductions seen in aspartate, ornithine and arginine during infection. In conclusion, we developed a model system of acute metabolic decompensation due to infection in a mouse model of a UCD. In addition, we have identified metabolic perturbations during infection in the spf-ash mice, including a reduction of urea cycle intermediates. This model of acute metabolic decompensation with HA due to infection in UCD serves as a platform for exploring biochemical perturbations and the efficacy of treatments, and could be adapted to explore acute decompensation in other

Molecular characterization of FXI deficiency.

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Berber, Ergul

2011-02-01

Factor XI (FXI) deficiency is a rare autosomal bleeding disease associated with genetic defects in the FXI gene. It is a heterogeneous disorder with variable tendency in bleeding and variable causative FXI gene mutations. It is characterized as a cross-reacting material-negative (CRM-) FXI deficiency due to decreased FXI levels or cross-reacting material-positive (CRM+) FXI deficiency due to impaired FXI function. Increasing number of mutations has been reported in FXI mutation database, and most of the mutations are affecting serine protease (SP) domain of the protein. Functional characterization for the mutations helps to better understand the molecular basis of FXI deficiency. Prevalence of the disease is higher in certain populations such as Ashkenazi Jews. The purpose of this review is to give an overview of the molecular basis of congenital FXI deficiency.

Orthodontic-surgical management of a case of severe mandibular deficiency due to condylar ankylosis

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Sridevi Padmanabhan

2014-01-01

Full Text Available Dentofacial deformities involve deviations from the normal facial proportions and dental relationships and can range from mild to being severe enough to be severely handicapping.The term handicapping malocclusions though not a term commonly used, involves a fortunately small section (2-4% of patients who can suffer from esthetic,psychological and functional problems. Craniofacial Orthodontics is the area of orthodontics that treats patients with congenital and acquired deformities of the integument and it′s underlying musculoskeletal system within the craniofacial area and associated structures.This case report of a young woman with severe mandibular deficiency and facial asymmetry due to condylar ankylosis highlights the importance of team work in rehabilitation of such severe craniofacial deformities.

An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency.

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Melek, Engin; Bulut, Fatma Derya; Atmış, Bahriye; Yılmaz, Berna Şeker; Bayazıt, Aysun Karabay; Mungan, Neslihan Önenli

2017-02-01

Carnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the β-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury.

Impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen metabolism

International Nuclear Information System (INIS)

Kirfel, Jutta; Pantelis, Dimitrios; Kabba, Mustapha; Kahl, Philip; Roeper, Anke; Kalff, Joerg C.; Buettner, Reinhard

2008-01-01

Four and one half LIM domain protein FHL2 participates in many cellular processes involved in tissue repair such as regulation of gene expression, cytoarchitecture, cell adhesion, migration and signal transduction. The repair process after wounding is initiated by the release of peptides and bioactive lipids. These molecules induce synthesis and deposition of a provisional extracellular matrix. We showed previously that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of FHL2 in response to activation of the RhoA GTPase. Our present study shows that FHL2 is an important signal transducer influencing the outcome of intestinal anastomotic healing. Early wound healing is accompanied by reconstitution and remodelling of the extracellular matrix and collagen is primarily responsible for wound strength. Our results show that impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen III metabolism. Impaired collagen III synthesis reduced the mechanical stability of the anastomoses and led to lower bursting pressure in Fhl2-deficient mice after surgery. Our data confirm that FHL2 is an important factor regulating collagen expression in the early phase of wound healing, and thereby is critically involved in the physiologic process of anastomosis healing after bowel surgery and thus may represent a new therapeutic target

Congenital rickets due to vitamin D deficiency in the mothers.

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Paterson, Colin R; Ayoub, David

2015-10-01

We wished to review all published reports of congenital rickets to identify the causes and characteristics. 25 cases were identified in 19 published reports in which there was radiological and/or histological evidence of rickets in the first two weeks after birth. Cases of rickets associated with maternal renal failure were excluded as were infants born at less than 32 weeks gestation. There was evidence of maternal deficiency in 24 of these cases. In 16 cases the diagnosis of the rickets led to the identification of symptomatic osteomalacia in the mothers. Of the 12 mothers who had assays for serum 25-hydroxyvitamin D (25OHD) 11 had values less than 10 ng/mL. Presentations in the infants included craniotabes, wide skull sutures, rachitic rosaries, enlargement of the wrists, tetany and convulsions. In two cases rickets had been suspected from antenatal X-rays. In five cases fractures were found at the time of initial presentation. Of the 16 infants with serum calcium assays 15 had values lower than 8.8 mg/dL. Of 13 infants who had serum alkaline phosphatase assays 12 had abnormally high levels. Of the seven infants in whom serum 25OHD was measured before treatment, all had values less than 10 ng/mL. These reports provide strong support for the view that maternal deficiency leads to overt bone disease from before birth. Maternal deficiency probably also leads to impairment of bone quality in postnatal life. The importance of ensuring adequate vitamin D nutrition in pregnancy is emphasised. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Galactose Epimerase Deficiency: Expanding the Phenotype

NARCIS (Netherlands)

Dias Costa, Filipa; Ferdinandusse, Sacha; Pinto, Carla; Dias, Andrea; Keldermans, Liesbeth; Quelhas, Dulce; Matthijs, Gert; Mooijer, Petra A.; Diogo, Luísa; Jaeken, Jaak; Garcia, Paula

2017-01-01

Galactose epimerase deficiency is an inborn error of metabolism due to uridine diphosphate-galactose-4'-epimerase (GALE) deficiency. We report the clinical presentation, genetic and biochemical studies in two siblings with generalized GALE deficiency.Patient 1: The first child was born with a

46,XY disorder of sex development due to 17-beta hydroxysteroid dehydrogenase type 3 deficiency: a plea for timely genetic testing.

Science.gov (United States)

Grimbly, Chelsey; Caluseriu, Oana; Metcalfe, Peter; Jetha, Mary M; Rosolowsky, Elizabeth T

2016-01-01

17β-hydroxysteroid dehydrogenase type 3 (17βHSD3) deficiency is a rare cause of disorder of sex development (DSD) due to impaired conversion of androstenedione to testosterone. Traditionally, the diagnosis was determined by βHCG-stimulated ratios of testosterone:androstenedione stimulation (1500 IU IM for 2 days) suggested 17βHSD3 deficiency although androstenedione was only minimally stimulated (4.5 nmol/L to 5.4 nmol/L). Expedient genetic testing for the HSD17B3 gene provided the unequivocal diagnosis. We advocate for urgent genetic testing in rare causes of DSD as indeterminate hormone results can delay diagnosis and prolong intervention.

Optimal management of iron deficiency anemia due to poor dietary intake

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García-López S

2011-10-01

Full Text Available Kattalin Aspuru1, Carlos Villa2, Fernando Bermejo2, Pilar Herrero3, Santiago García López1 1Digestive Department, Hospital Universitario Miguel Servet (Miguel Servet University Hospital, Zaragoza, 2Digestive Department, Hospital Universitario de Fuenlabrada (Fuenlabrada University Hospital, Madrid, 3Professional College of Nutritionists and Dietitians of Aragon, Zaragoza, Spain Abstract: Iron is necessary for the normal development of multiple vital processes. Iron deficiency (ID may be caused by several diseases, even by physiological situations that increase requirements for this mineral. One of its possible causes is a poor dietary iron intake, which is infrequent in developed countries, but quite common in developing areas. In these countries, dietary ID is highly prevalent and comprises a real public health problem and a challenge for health authorities. ID, with or without anemia, can cause important symptoms that are not only physical, but can also include a decreased intellectual performance. All this, together with a high prevalence, can even have negative implications for a community’s economic and social development. Treatment consists of iron supplements. Prevention of ID obviously lies in increasing the dietary intake of iron, which can be difficult in developing countries. In these regions, foods with greater iron content are scarce, and attempts are made to compensate this by fortifying staple foods with iron. The effectiveness of this strategy is endorsed by multiple studies. On the other hand, in developed countries, ID with or without anemia is nearly always associated with diseases that trigger a negative balance between iron absorption and loss. Its management will be based on the treatment of underlying diseases, as well as on oral iron supplements, although these latter are limited by their tolerance and low potency, which on occasions may compel a change to intravenous administration. Iron deficiency has a series of

Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on bone mineral density

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Daripa M.

2004-01-01

Full Text Available The objective of the present study was to determine the effect of chronic calcitonin deficiency on bone mass development. The results of 11 patients with thyroid dysgenesis (TD were compared to those of 17 normal individuals (C and of 9 patients with other forms of hypothyroidism (OH: 4 with hypothyroidism due to inborn errors of thyroid hormone synthesis and 5 with Hashimoto's thyroiditis. The subjects received an intravenous calcium stimulus and blood was collected for the determination of ionized calcium (Ca2+, calcitonin, and intact parathyroid hormone. Bone mineral density (BMD was determined by dual-energy X-ray absorptiometry. After calcium administration the levels of Ca2+ in the two groups of hypothyroidism were significantly higher than in the normal control group (10 min after starting calcium infusion: C = 1.29 ± 0.08 vs TD = 1.34 ± 0.03 vs OH = 1.34 ± 0.02 mmol/l; P < 0.05, and only the TD group showed no calcitonin response (5 min after starting calcium infusion: C = 27.9 ± 5.8 vs TD = 6.6 ± 0.3 vs OH = 43.0 ± 13.4 ng/l. BMD values did not differ significantly between groups (L2-L4: C = 1.116 ± 0.02 vs TD = 1.109 ± 0.03 vs OH = 1.050 ± 0.04 g/cm². These results indicate that early deficiency of calcitonin secretion has no detrimental effect on bone mass development. Furthermore, the increased calcitonin secretion observed in patients with inborn errors of thyroid hormone biosynthesis does not confer any advantage in terms of BMD.

Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment.

OpenAIRE

Lever, E G; Elwes, R D; Williams, A; Reynolds, E H

1986-01-01

Subacute combined degeneration of the cord is a rare complication of folate deficiency. Disturbance of methylation reactions in nervous tissue probably underlie subacute combined degeneration of the cord arising from folate as well as vitamin B12 deficiency. Methyl tetrahydrofolate is the form in which folic acid is transported into the CNS. Therefore methyl tetrahydrofolate treatment of the neurological and psychiatric manifestations of folate deficiency would seem to be theoretically advant...

Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

International Nuclear Information System (INIS)

Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M.

1990-01-01

Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications

Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M. (Stanford Univ. School of Medicine, CA (USA))

1990-10-01

Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.

Roux-en-Y gastric bypass in the treatment of non-classic congenital adrenal hyperplasia due to 11-hydroxylase deficiency.

Science.gov (United States)

Kalani, Amir; Thomas, Nithin; Sacerdote, Alan; Bahtiyar, Gül

2013-03-18

Non-classic adrenal hyperplasia (NCAH) has been associated with insulin resistance (IR). Therapies such as metformin, thiazolidinediones and lifestyle alterations improve IR and also ameliorate the biochemical and clinical abnormalities of NCAH, much as they do in polycystic ovarian syndrome (PCOS). More recently, bariatric surgery, such as Roux-en-Y gastric bypass (RYGBP), has also been associated with improvement in IR and amelioration of PCOS and may, therefore, be beneficial in NCAH. We report a case of a 39-year-old, deaf-mute, obese woman with NCAH due to 11-hydroxylase deficiency who underwent RYGBP followed by improvement of NCAH manifestations. She was initially treated with metformin and pioglitazone, which lowered serum 11-deoxycortisol from 198 ng/dl (irregular menses normalised as well. We conclude that RYGBP, like other interventions that reduce IR, may be another way of treating non-classic 11-hydroxylase deficiency in selected patients.

Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

Science.gov (United States)

Ishibashi, S; Yokota, T; Shiojiri, T; Matunaga, T; Tanaka, H; Nishina, K; Hirota, H; Inaba, A; Yamada, M; Kanda, T; Mizusawa, H

2003-05-01

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Osteopetrorickets due to Snx10 deficiency in mice results from both failed osteoclast activity and loss of gastric acid-dependent calcium absorption.

Directory of Open Access Journals (Sweden)

Liang Ye

2015-03-01

Full Text Available Mutations in sorting nexin 10 (Snx10 have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficient osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis (due to osteoclast defect and rickets (due to high stomach pH and low calcium availability, resulting in impaired bone mineralization. Osteopetrorickets, the paradoxical association of insufficient mineralization in the context of a positive total body calcium balance, is thought to occur due to the inability of the osteoclasts to maintain normal calcium-phosphorus homeostasis. However, osteoclast-specific Snx10 knockout had no effect on calcium balance, and therefore led to severe osteopetrosis without rickets. Moreover, supplementation with calcium gluconate rescued mice from the rachitic phenotype and dramatically extended life span in global Snx10-deficient mice, suggesting that this may be a life-saving component of the clinical approach to Snx10-dependent human osteopetrosis that has previously gone unrecognized. We conclude that tissue-specific effects of Snx10 mutation need to be considered in clinical approaches to this disease entity. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. These studies established an essential role for Snx10 in bone homeostasis and underscore the importance of gastric acidification in calcium uptake.

Isolated adrenocorticotropic hormone deficiency due to probable lymphocytic hypophysitis in a woman

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Faten Hadj Kacem

2013-01-01

Full Text Available We report a 22-year-old woman who presented with asthenia, weight loss and hypotension in which extensive pituitary and adrenal investigations were diagnostic of isolated adrenocorticotropic hormone deficiency (IAD of pituitary origin. Magnetic resonance imaging of the hypothalamus and pituitary showed a normal-sized pituitary, with no mass lesion. The diagnosis of IAD probably secondary to lymphocytic hypophysitis (LYH was made.IAD is able to be the way of presentation of LYH, although the disease could or could not turn into a panhypopituitarism. Prompt recognition of this potentially fatal condition is important because of the availability of effective treatment. Indeed, regular endocrine and imaging follow up is important for patients with IAD and normal initial pituitary imaging results to detect early new-onset pituitary hormones deficiencies or imaging abnormalities.

Rickets–vitamin D deficiency and dependency

Science.gov (United States)

Sahay, Manisha; Sahay, Rakesh

2012-01-01

Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal. PMID:22470851

Rickets-vitamin D deficiency and dependency

Directory of Open Access Journals (Sweden)

Manisha Sahay

2012-01-01

Full Text Available Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal.

Zinc Deficiency in Humans and its Amelioration

OpenAIRE

Yashbir Singh Shivay

2015-01-01

Zinc (Zn) deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in ...

Clinical significance of enzymatic deficiencies in the gastrointestinal tract with particular reference to lactase deficiency.

Science.gov (United States)

Rossi, E; Lentze, M J

1984-12-01

The study of deficiencies of small intestinal brush-border hydrolases increased our knowledge about the specific functions of hydrolases in the digestion of smaller molecules on the microvillus surface of the absorptive cells. The sucrase-isomaltase (SI) complex has been shown to be synthesized as a precursor (pro-sucrase-isomaltase) which is then incorporated into the membrane. The hydrophobic N-terminal end of the molecule is anchored in the lipid bilayer. In SI deficiency the molecular base of the disease is still not clear. Absence of SI activity could be due to complete lack of precursor synthesis or to structural changes within the N-terminal end of the SI-complex. Deficiencies of peptide hydrolases have not been reported with the exception of enteropeptidase (EP). Here a congenital deficiency of the enzyme was observed as the primary defect in enzyme synthesis within the enterocytes and as a secondary defect due to exocrine pancreatic insufficiency. In contrast to the primary EP deficiency, the activity of EP can be restored in the cases of exocrine pancreatic insufficiency by treatment with pancreatic extracts. Primary lactase deficiency exists in various forms. Besides congenital lactase deficiency, the late onset or adult type of lactase deficiency has been observed. The latter occurs in many different ethnic groups around the world. Here, using gel electrophoresis and immunoelectrophoresis, the lack of enzyme activity could be shown to be a primary defect in enzyme protein synthesis. In man and in the rat, two different lactases have been identified. In contrast to adult lactase, fetal lactase contains sialic acid at the end of carbohydrate side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Implantes cocleares em crianças portadoras de deficiência auditiva decorrente de meningite Cochlear implant in deaf children due to meningites

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Maria C. Bevilacqua

2003-12-01

Full Text Available A meningite é a principal causa de deficiência auditiva neurossensorial adquirida, o paciente pode apresentar ao mesmo tempo déficit motor, distúrbio visual, distúrbio de linguagem, déficit vestibular, déficit de atenção e incapacidade para a aprendizagem. Caracteristicamente a deficiência auditiva pós-meningite é sensorioneural, profunda, bilateral, simétrica e descendente, mais comum no sexo masculino e em crianças abaixo de 5 anos e traz não só graves implicações quanto ao desenvolvimento social e emocional dos sujeitos por ela afetados, como também sérias alterações na linguagem oral já adquirida e/ou em estágio de aquisição. OBJETIVO: O trabalho objetiva realizar um estudo comparativo de um grupo de crianças com deficiência auditiva sensorioneural devido a meningite e um grupo de crianças com deficiência auditiva sensorioneural de etiologias diversas, implantadas no período pré-lingual, na faixa etária de 1 ano e 10 meses a 6 anos. FORMA DE ESTUDO: Coorte transversal. MATERIAL E MÉTODO: Foram avaliadas 63 crianças com deficiência auditiva neurossensorial profunda bilateral pré-lingual, usuárias de implante coclear multicanal, sendo 25 (40% do sexo masculino 38 (60% do sexo feminino. Em 12 casos (19% a deficiência auditiva foi decorrente da meningite e em 51 casos (81% de outras etiologias. Todos os indivíduos selecionados foram submetidos a avaliações otorrinolaringológicas e audiológicas clínicas e objetivas. CONCLUSÕES: A ocorrência de inserção parcial dos eletrodos foi maior no grupo com deficiência auditiva pós-meningite. Não houve diferenças estatisticamente significantes quanto ao reconhecimento de palavras e fonemas e nos questionários de avaliação das habilidades auditivas (MAIS e de linguagem (MUSS entre os grupos estudados.Meningitis is the main cause of acquired sensorineural hearing loss in children. The patient may also present motor disorders, visual, vestibular, language

Subdural hemorrhage: A unique case involving secondary vitamin K deficiency bleeding due to biliary atresia.

Science.gov (United States)

Miyao, Masashi; Abiru, Hitoshi; Ozeki, Munetaka; Kotani, Hirokazu; Tsuruyama, Tatsuaki; Kobayashi, Naho; Omae, Tadaki; Osamura, Toshio; Tamaki, Keiji

2012-09-10

Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hyponatremia in aneurysmal subarachnoid hemorrhage is due to the syndrome of inappropriate antidiuresis and acute glucocorticoid deficiency

LENUS (Irish Health Repository)

Hannon, M J

2011-06-01

Hyponatraemia is the most common electrolyte abnormality following subarachnoid haemorrhage (SAH) and contributes to increased morbidity and mortality. Retrospective data suggests that the syndrome of inappropriate diuresis (SIAD) is the most common cause of hyponatraemia in SAH, though cerebral salt wasting has been postulated by some workers to be the predominant abnormality. Data which has shown acute glucocorticoid deficiency following SAH has suggested that some cases of euvolaemic hyponatraemia may also be caused by this mechanism.We prospectively studied the hormonal and haemodynamic influences involved in the development of hyponatraemia in 100 patients (61% female, median age 53 (range 16-82)) with non-traumatic aneurysmal SAH. Each patient had plasma sodium (pNa), urea, osmolality, glucose and 0900h cortisol (PC), and urinary sodium and osmolality measured on days 1, 2, 3, 4, 6, 8, 10 and 12 following SAH. Fluid balance and haemodynamic parameters were recorded daily. Results were compared with 15 patients admitted to ITU following vascular surgery. A PC<300nmol\\/L in a patient in ITU was regarded clinically as inappropriately low.49% of patients developed hyponatraemia (pNa<135 mmol\\/L), including 14% who developed clinically significantly hyponatraemia (pNa<130 mmol\\/L). 36\\/49 (73.4%) developed hyponatraemia between days 1 and 3 post SAH. The median duration of hyponatraemia was 3 days (range 1–10 days).In 35\\/49 (71.4%), hyponatraemia was due to SIAD as defined by standard diagnostic criteria. 14% of SAH patients had at least one PC<300nmol\\/L; 5 of these (35.7%) developed hyponatraemia. In 4 patients hyponatraemia was preceded by acute cortisol deficiency and responded to hydrocortisone treatment. In contrast, all controls had PC>500 nmol\\/L on day 1, and >300 nmol on days 3–12. There were no cases of cerebral salt wasting. There was no relationship between the incidence of hyponatraemia and the defined anatomical territory or severity of

Fulminant lipid storage myopathy due to multiple acyl-coenzyme a dehydrogenase deficiency.

Science.gov (United States)

Whitaker, Charles H; Felice, Kevin J; Silvers, David; Wu, Qian

2015-08-01

The lipid storage myopathies, primary carnitine deficiency, neutral lipid storage disease, and multiple acyl coenzyme A dehydrogenase deficiency (MADD), are progressive disorders that cause permanent weakness. These disorders of fatty acid metabolism and intracellular triglyceride degradation cause marked fat deposition and damage to muscle cells. We describe a rapidly progressive myopathy in a previously healthy 33-year-old woman. Over 4 months, she developed a proximal and axial myopathy associated with diffuse myalgia and dysphagia, ultimately leading to respiratory failure and death. Muscle biopsy showed massive accumulation of lipid. Plasma acylcarnitine and urine organic acid analysis was consistent with MADD. This was confirmed by molecular genetic testing, which revealed 2 pathogenic mutations in the ETFDH gene. This report illustrates a late-onset case of MADD and reviews the differential diagnosis and evaluation of patients with proximal myopathy and excessive accumulation of lipid on muscle biopsy. © 2014 Wiley Periodicals, Inc.

Human hypocretin-deficient narcolepsy - aberrant food choice due to impaired taste?

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Giselle de Martin Truzzi

Full Text Available Authors demonstrate that patients with narcolepsy type 1 (N1 have more tendency of eat salty snacks after satiety than health volunteers. A few mechanisms to explain the weight gain have been discussed in narcolepsy. The hypocretin-1 deficiency can influence the olfactory system. The olfactory system should be modulated through hypocretin-1 via connections from the hypothalamic to other brain regions. Likewise, hypocretin-1 can be synthesized locally in our olfactory mucosa with possible private role modulating the olfactory. In experimental studies, different kinds of smell influence the preference for type of diet. Olfactory and taste sensations help control of appetite and regulate the quantity and quality of foods that will be chosen. N1 patients have lower levels of hypocretin-1 and consequent inferior olfactory threshold, less olfactory discrimination, and these findings improved after nasal hypocretin-1 administration. It is possible that the hyposmia influenced the quality and quantity of food by narcoleptic patients. We suggest that a complementary analysis of olfactory function should be done concomitant with food preferences to compare narcoleptic patients with and without hypocretin-1 deficiency.

Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency

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Nadia Mohd Effendy

2012-01-01

Full Text Available Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT. However, one medicinal plant, Eurycoma longifolia Jack (EL, can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.

Toward reassessing data-deficient species.

Science.gov (United States)

Bland, Lucie M; Bielby, Jon; Kearney, Stephen; Orme, C David L; Watson, James E M; Collen, Ben

2017-06-01

One in 6 species (13,465 species) on the International Union for Conservation of Nature (IUCN) Red List is classified as data deficient due to lack of information on their taxonomy, population status, or impact of threats. Despite the chance that many are at high risk of extinction, data-deficient species are typically excluded from global and local conservation priorities, as well as funding schemes. The number of data-deficient species will greatly increase as the IUCN Red List becomes more inclusive of poorly known and speciose groups. A strategic approach is urgently needed to enhance the conservation value of data-deficient assessments. To develop this, we reviewed 2879 data-deficient assessments in 6 animal groups and identified 8 main justifications for assigning data-deficient status (type series, few records, old records, uncertain provenance, uncertain population status or distribution, uncertain threats, taxonomic uncertainty, and new species). Assigning a consistent set of justification tags (i.e., consistent assignment to assessment justifications) to species classified as data deficient is a simple way to achieve more strategic assessments. Such tags would clarify the causes of data deficiency; facilitate the prediction of extinction risk; facilitate comparisons of data deficiency among taxonomic groups; and help prioritize species for reassessment. With renewed efforts, it could be straightforward to prevent thousands of data-deficient species slipping unnoticed toward extinction. © 2016 Society for Conservation Biology.

Maternal vitamin D deficiency: a culprit for hypocalcaemia induced ...

African Journals Online (AJOL)

Background: A rare but reversible cause of dilated cardiomyopathy occurs in infants born to vitamin D deficient mothers due to hypocalcaemia. Case Report: We report a case of dilated cardiomyopathy due to hypocalcaemia secondary to maternal vitamin D deficiency in an infant presented with seizure disorder and heart ...

Metabolic stabilization of acetylcholine receptors in vertebrate neuromuscular junction by muscle activity

International Nuclear Information System (INIS)

Rotzler, S.; Brenner, H.R.

1990-01-01

The effects of muscle activity on the growth of synaptic acetylcholine receptor (AChR) accumulations and on the metabolic AChR stability were investigated in rat skeletal muscle. Ectopic end plates induced surgically in adult soleus muscle were denervated early during development when junctional AChR number and stability were still low and, subsequently, muscles were either left inactive or they were kept active by chronic exogenous stimulation. AChR numbers per ectopic AChR cluster and AChR stabilities were estimated from the radioactivity and its decay with time, respectively, of end plate sites whose AChRs had been labeled with 125 I-alpha-bungarotoxin (alpha-butx). The results show that the metabolic stability of the AChRs in ectopic clusters is reversibly increased by muscle activity even when innervation is eliminated very early in development. 1 d of stimulation is sufficient to stabilize the AChRs in ectopic AChR clusters. Muscle stimulation also produced an increase in the number of AChRs at early denervated end plates. Activity-induced cluster growth occurs mainly by an increase in area rather than in AChR density, and for at least 10 d after denervation is comparable to that in normally developing ectopic end plates. The possible involvement of AChR stabilization in end plate growth is discussed

Congenital Adrenal Hyperplasia due to 17-alpha-hydoxylase/17,20-lyase Deficiency Presenting with Hypertension and Pseudohermaphroditism: First Case Report from Oman

Directory of Open Access Journals (Sweden)

Waad-Allah S. Mula-Abed

2014-01-01

Full Text Available This is the first report of congenital adrenal hyperplasia (CAH due to combined 17α-hydroxylase/17,20 lyase deficiency in an Omani patient who was initially treated for many years as a case of hypertension. CAH is an uncommon disorder that results from a defect in steroid hormones biosynthesis in the adrenal cortex. The clinical presentation depends on the site of enzymatic mutations and the types of accumulated steroid precursors. A 22-year-old woman who was diagnosed to have hypertension since the age of 10 years who was treated with anti-hypertensive therapy was referred to the National Diabetes and Endocrine Centre, Royal Hospital, Oman. The patient also had primary amenorrhea and features of sexual infantilism. Full laboratory and radio-imaging investigations were done. Adrenal steroids, pituitary function and karyotyping study were performed and the diagnosis was confirmed by molecular mutation study. Laboratory investigations revealed adrenal steroids and pituitary hormones profile in addition to 46XY karyotype that are consistent with the diagnosis of CAH due to 17α-hydroxylase deficiency. Extensive laboratory workup revealed low levels of serum cortisol (and its precursors 17α-hydroxyprogesterone and 11-deoxycortisol, adrenal androgens (dehydroepiandrosterone sulfate and androstenedione, and estrogen (estradiol; and high levels of mineralocorticoids precursors (11-deoxycorticosterone and corticosterone with high levels of ACTH, FSH and LH. Mutation analysis revealed CYP17A1-homozygous mutation (c.287G>A p.Arg96Gln resulting in the complete absence of 17α-hydroxylase/17,20-lyase activity. The patient was treated with dexamethasone and ethinyl estradiol with cessation of anti-hypertensive therapy. A review of the literature was conducted to identify previous studies related to this subtype of CAH. This is the first biochemically and genetically proven case of CAH due to 17α-hydroxylase/17,20-lyase deficiency in Oman and in the Arab

Iodine-deficiency disorders

NARCIS (Netherlands)

Zimmermann, M.B.; Jooste, P.L.; Pandav, C.S.

2008-01-01

billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed

Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1

DEFF Research Database (Denmark)

Carrozzo, Rosalba; Verrigni, Daniela; Rasmussen, Magnhild

2016-01-01

BACKGROUND: The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate-CoA ligase, caused by mutations in SUCLA2 or SUCLG1. We report here 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings...... deficiency of complexes I and IV, but normal histological and biochemical findings in muscle did not preclude a diagnosis of succinate-CoA ligase deficiency. In five patients, the urinary excretion of methylmalonic acid was only marginally elevated, whereas elevated plasma methylmalonic acid was consistently...

Vitamin C deficiency in weanling guinea pigs

DEFF Research Database (Denmark)

Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E.

2007-01-01

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... increased, while protein oxidation decreased (P¼0003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during...

Veganism as a cause of iodine deficient hypothyroidism.

Science.gov (United States)

Yeliosof, Olga; Silverman, Lawrence A

2018-01-26

Iodine deficiency is the most common cause of acquired hypothyroidism worldwide. Although uncommon in the Western world, the incidence of iodine deficiency may be rising due to the increased use of restrictive diets. We present a 23-month-old boy diagnosed with iodine deficiency hypothyroidism, induced by a vegan diet. This case highlights the risk for iodine deficiency in children on a vegan diet after discontinuation of breast/formula feeding that could lead to acquired hypothyroidism.

Genetic, molecular and functional analyses of complement factor I deficiency

DEFF Research Database (Denmark)

Nilsson, S.C.; Trouw, L.A.; Renault, N.

2009-01-01

Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast.

Directory of Open Access Journals (Sweden)

2005-11-01

Full Text Available A model for replicative life span extension by calorie restriction (CR in yeast has been proposed whereby reduced glucose in the growth medium leads to activation of the NAD-dependent histone deacetylase Sir2. One mechanism proposed for this putative activation of Sir2 is that CR enhances the rate of respiration, in turn leading to altered levels of NAD or NADH, and ultimately resulting in enhanced Sir2 activity. An alternative mechanism has been proposed in which CR decreases levels of the Sir2 inhibitor nicotinamide through increased expression of the gene coding for nicotinamidase, PNC1. We have previously reported that life span extension by CR is not dependent on Sir2 in the long-lived BY4742 strain background. Here we have determined the requirement for respiration and the effect of nicotinamide levels on life span extension by CR. We find that CR confers robust life span extension in respiratory-deficient cells independent of strain background, and moreover, suppresses the premature mortality associated with loss of mitochondrial DNA in the short-lived PSY316 strain. Addition of nicotinamide to the medium dramatically shortens the life span of wild type cells, due to inhibition of Sir2. However, even in cells lacking both Sir2 and the replication fork block protein Fob1, nicotinamide partially prevents life span extension by CR. These findings (1 demonstrate that respiration is not required for the longevity benefits of CR in yeast, (2 show that nicotinamide inhibits life span extension by CR through a Sir2-independent mechanism, and (3 suggest that CR acts through a conserved, Sir2-independent mechanism in both PSY316 and BY4742.

Increased life span due to calorie restriction in respiratory-deficient yeast.

Directory of Open Access Journals (Sweden)

Matt Kaeberlein

2005-11-01

Full Text Available A model for replicative life span extension by calorie restriction (CR in yeast has been proposed whereby reduced glucose in the growth medium leads to activation of the NAD+-dependent histone deacetylase Sir2. One mechanism proposed for this putative activation of Sir2 is that CR enhances the rate of respiration, in turn leading to altered levels of NAD+ or NADH, and ultimately resulting in enhanced Sir2 activity. An alternative mechanism has been proposed in which CR decreases levels of the Sir2 inhibitor nicotinamide through increased expression of the gene coding for nicotinamidase, PNC1. We have previously reported that life span extension by CR is not dependent on Sir2 in the long-lived BY4742 strain background. Here we have determined the requirement for respiration and the effect of nicotinamide levels on life span extension by CR. We find that CR confers robust life span extension in respiratory-deficient cells independent of strain background, and moreover, suppresses the premature mortality associated with loss of mitochondrial DNA in the short-lived PSY316 strain. Addition of nicotinamide to the medium dramatically shortens the life span of wild type cells, due to inhibition of Sir2. However, even in cells lacking both Sir2 and the replication fork block protein Fob1, nicotinamide partially prevents life span extension by CR. These findings (1 demonstrate that respiration is not required for the longevity benefits of CR in yeast, (2 show that nicotinamide inhibits life span extension by CR through a Sir2-independent mechanism, and (3 suggest that CR acts through a conserved, Sir2-independent mechanism in both PSY316 and BY4742.

METHYLMALONIC ACID AND HOMOCYSTEIN SERUM IN DIAGNOSING MEGALOBLASTIC ANEMIA DUE TO COBALAMIN AND FOLATE DEFICIENCY IN TRAVEL MEDICINE

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Made Gian Indra Rahayuda

2014-01-01

Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Anemia is a major global health problem, especially in developing countries. Anemia is a condition where the red blood cell mass and / or hemoglobin mass that circulating in the body was decreased to below normal level so it can not function well in providing oxygen to the body tissues. One of the most common type is megaloblastic anemia. Megaloblastic anemia is mostly caused by vitamin B12 (cobalamin and folate deficiency. One of the causes of cobalamin and folate deficiency anemia is tropical sprue. Cobalamin deficiency anemia and folate deficiency anemia gives a similar symptom, but in cobalamin deficiency there is neuropathy symptoms. Normal serum folate is between 3-15 ng/mL. Normal folate erythrocyte is 150-600 ng/mL. In cobalamin deficiency, serum cobalamin decreased below the cut off point 100pg/mL (normally 100 - 400pg/mL. Other examination such as elevated homocysteine??, methylmalonic acid, or formioglutamic acid (FIGLU in the urine can confirm the diagnosis of cobalamin and folic acid deficiency. There is no consensus on the cut-off point of homocysteine ??and MMA. Homocysteine ??has been considered to increase when the levels are above 12-14 ?mol /L in women and in the 14-15 ?mol/L. According to research by Robert et al in the case of cobalamin deficiency, serum tHcy> 15.0 ?mol/L. Most research considers the increase of MMA in cobalamin deficiency is> 0:28 ?mol / L, but the cut off point in circulation varies between 0:21 to 0:48 ?mol/L. MMA level is increased in serum and urine in cobalamin deficiency, whereas MMA normal in folate deficiency. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font

A new approach for the molecular epitope identification in protein antigens by combination of partial proteolytic digestion of an immobilized immune complex with mass spectrometric peptide mapping

International Nuclear Information System (INIS)

Fiedler, W.; Etspueler, H.; Suckau, D.; Przybylski, M.

1992-01-01

The most widely used routine test for the detection of antibodies against the acetylcholine receptor (AChR) in sera from patients with myasthenia gravis (MG) employs human amputates as antigen source (AChR AMP ). From the results of the study we conclude that the TE671 assay is a useful alternative to the conventional assay using AChR from amputated muscle, as AChR TE671 is more homogeneous, more readily available, and safer than AChR AMP prepared from potentially infection material. However, there are important differences between the two assays, namely a higher cut off point for AChR TE671 and by one third lower AChR TE671 titers in patients with generalized myasthenia. (orig.)

Inherited protein S deficiency due to a novel nonsense mutation in the PROS1 gene in the patient with recurrent vascular access thrombosis: A case report

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Eun Jin Cho

2012-03-01

Full Text Available Vascular access thrombosis is one of the major causes of morbidity in patients maintained on chronic hemodialysis. Thrombophilia has been recognized as a risk factor of vascular access thrombosis. The authors report a case of inherited protein S deficiency associated with vascular access thrombotic events. DNA sequence analysis of the PROS1 gene identified a novel heterozygous nonsense mutation in exon 10 by transition of AAG (lysine to TAG (stop codon at codon 473 (c.1417A>T, p.K473X. Results from the study suggest that the inherited protein S deficiency due to a PROS1 gene mutation may cause vascular access thrombosis in hemodialysis patients.

In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

Science.gov (United States)

Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

2015-01-01

A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong

The Evidence-Based Evaluation of Iron Deficiency Anemia.

Science.gov (United States)

Hempel, Eliana V; Bollard, Edward R

2016-09-01

Anemia is a prevalent disease with multiple possible etiologies and resultant complications. Iron deficiency anemia is a common cause of anemia and is typically due to insufficient intake, poor absorption, or overt or occult blood loss. Distinguishing iron deficiency from other causes of anemia is integral to initiating the appropriate treatment. In addition, identifying the underlying cause of iron deficiency is also necessary to help guide management of these patients. We review the key components to an evidence-based, cost-conscious evaluation of suspected iron deficiency anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

[Hyperammonemia due to ornithine transcarbamylase deficiency--a cause of lethal metabolic crisis during the newborn period and infancy (author's transl)].

Science.gov (United States)

Schuchmann, L; Colombo, J P; Fischer, H

1980-05-01

A severe hyperammonemia is the characteristic finding in patients with enzyme defects in urea cycle and one of the main causes of the acute metabolic crisis dsuring the newborn period and infancy. A case report is given about two male infants, who died in the age of one and of seven months respectively. In the second child the blood ammonia concentration raised up to 833 micrograms/100 ml, and, OTC deficiency was diagnosed due to enzyme determination in liver biopsie. Probably, the first child, that also died as newborn, suffered from the same disease. In this case, only post mortem findings are available.

Clinical, Biochemical, and Molecular Spectrum of Hyperargininemia Due to Arginase I Deficiency

OpenAIRE

Scaglia, Fernando; Lee, Brendan

2006-01-01

The urea cycle consists of six consecutive enzymatic reactions that convert waste nitrogen into urea. Urea cycle disorders are a group of inborn errors of hepatic metabolism that often result in life threatening hyperammonemia and hyperglutaminemia. Deficiencies of all of the enzymes of the cycle have been described and although each specific disorder results in the accumulation of different precursors, hyperammonemia and hyperglutaminemia are common biochemical hallmarks of these disorders. ...

In HepG2 Cells, Coexisting Carnitine Deficiency Masks Important Indicators of Marginal Biotin Deficiency123

Science.gov (United States)

Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

2015-01-01

Background: A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. Objective: In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. Methods: We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography–tandem mass spectrometry. Results: Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased

How common is vitamin B-12 deficiency?

Science.gov (United States)

Allen, Lindsay H

2009-02-01

In considering the vitamin B-12 fortification of flour, it is important to know who is at risk of vitamin B-12 deficiency and whether those individuals would benefit from flour fortification. This article reviews current knowledge of the prevalence and causes of vitamin B-12 deficiency and considers whether fortification would improve the status of deficient subgroups of the population. In large surveys in the United States and the United Kingdom, approximately 6% of those aged > or =60 y are vitamin B-12 deficient (plasma vitamin B-12 life. In developing countries, deficiency is much more common, starting in early life and persisting across the life span. Inadequate intake, due to low consumption of animal-source foods, is the main cause of low serum vitamin B-12 in younger adults and likely the main cause in poor populations worldwide; in most studies, serum vitamin B-12 concentration is correlated with intake of this vitamin. In older persons, food-bound cobalamin malabsorption becomes the predominant cause of deficiency, at least in part due to gastric atrophy, but it is likely that most elderly can absorb the vitamin from fortified food. Fortification of flour with vitamin B-12 is likely to improve the status of most persons with low stores of this vitamin. However, intervention studies are still needed to assess efficacy and functional benefits of increasing intake of the amounts likely to be consumed in flour, including in elderly persons with varying degrees of gastric atrophy.

Dermatitis and optic neuropathy due to zinc deficiency after malabsortive bariatric surgery

OpenAIRE

Ramos-Leví, Ana M.; Sánchez-Pemaute, Andrés; Rubio Herrera, Miguel A.

2013-01-01

We present a patient who underwent successful classic duodenal switch and developed a marked dermatitis with a significant functional limitation. This is an unusual complication, despite the relatively moderate prevalence of nutrient deficiency after this type of bariatric surgery. We discuss possible pathogenic mechanisms and emphasize the importance of an appropriate nutritional management. Se presenta el caso de una mujer sometida a cirugía bariátrica malabsortiva que desarrolló una lla...

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Science.gov (United States)

Khattab, Ahmed; Haider, Shozeb; Kumar, Ameet; Dhawan, Samarth; Alam, Dauood; Romero, Raquel; Burns, James; Li, Di; Estatico, Jessica; Rahi, Simran; Fatima, Saleel; Alzahrani, Ali; Hafez, Mona; Musa, Noha; Razzghy Azar, Maryam; Khaloul, Najoua; Gribaa, Moez; Saad, Ali; Charfeddine, Ilhem Ben; Bilharinho de Mendonça, Berenice; Belgorosky, Alicia; Dumic, Katja; Dumic, Miroslav; Aisenberg, Javier; Kandemir, Nurgun; Alikasifoglu, Ayfer; Ozon, Alev; Gonc, Nazli; Cheng, Tina; Kuhnle-Krahl, Ursula; Cappa, Marco; Holterhus, Paul-Martin; Nour, Munier A; Pacaud, Daniele; Holtzman, Assaf; Li, Sun; Zaidi, Mone; Yuen, Tony; New, Maria I

2017-03-07

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1 , a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.

Panhypopituitarism Due to Hemochromatosis

OpenAIRE

Mesut Özkaya; Kadir Gis; Ali Çetinkaya

2013-01-01

Hemochromatosis is an iron storage disease. Panhypopituitarism is a clinical condition in which the anterior pituitary hormones are deficient. Herein, we report a rare case of panhypopituitarism due to hemochromatosis. Turk Jem 2013; 17: 125-6

An iron-deficient diet stimulates the onset of the hepatitis due to hepatic copper deposition in the Long-Evans Cinnamon (LEC) rat

Energy Technology Data Exchange (ETDEWEB)

Sugawara, Naoki; Sugawara, Chieko [Sapporo Medical Univ. (Japan). Dept. of Public Health

1999-09-01

To study effects of dietary Cu and Fe levels on the onset of hepatitis in Long-Evans Cinnamon (LEC) rats, female rats (40 days old) were fed a semipurified diet containing 0.1 or 10 mg Cu/kg and 1.5 or 150 mg Fe/kg in a 2 x 2 factorial arrangement for 35 days. At 75 days after birth, LEC rats (+Cu-Fe) fed a Cu-sufficient but Fe-deficient diet (Cu, 10 mg/kg; Fe, 1.5 mg/kg) showed jaundice, with lethargy, anorexia, and malaise. The biochemical variables relating to liver function were significantly increased compared to three other groups, a Cu- and Fe-deficient (-Cu-Fe) group, a Cu-deficient but Fe-sufficient (-Cu+Fe) group, and a Cu and Fe sufficient (+Cu+Fe) group. Furthermore, the +Cu-Fe rat liver showed massive necrosis with huge nuclei. The other three groups presented no biochemical and histological findings of hepatitis. Hepatic Cu and metallothionein concentrations were 289 {+-} 87 (mean {+-} SD) {mu}g/g liver and 8.7 {+-} 1.8 mg/g liver, respectively, in the +Cu-Fe rats. However, in the +Cu+Fe group the values were 196 {+-} 28 {mu}g Cu/g liver and 10.8 {+-} 1.0 mg/g liver. Hepatic Fe deposition was not influenced significantly by the dietary Cu level. The +Cu-Fe group with jaundice showed the highest free Cu concentration in the liver among the four groups, but the hepatic free Fe concentration was similar to those in the -Cu+Fe and +Cu+Fe groups. Our results indicate that an Fe-deficient diet enhances the deposition of hepatic Cu due to increased absorption of Cu from the gastrointestinal tract. This deposition stimulated the onset of hepatitis. (orig.)

Surgical evacuation of neonatal intracranial hemorrhage due to vitamin K deficiency bleeding.

Science.gov (United States)

Zidan, Ashraf Shaker; Abdel-Hady, Hesham

2011-03-01

Although the incidence of vitamin K deficiency bleeding (VKDB) in neonates has dramatically decreased in the developed world since the adoption of routine vitamin K prophylaxis, in developing countries the incidence is still high. Intracranial hemorrhage (ICH) is the most dangerous complication. Early recognition and management are important to decrease the mortality rate and neurological sequelae. The authors conducted a prospective study between January 2008 and June 2010. They included all full-term neonates referred to the Department of Neurosurgery at Mansoura University Children's Hospital with ICH complicating VKDB and necessitating surgical evacuation. The objective was to evaluate the clinical presentation, diagnosis, hospital course, and outcome of ICH in full-term neonates with VKDB after surgical evacuation. Thirty-two neonates with ICH due to VKDB were included. Diagnosis and classification of ICH were based on detailed history, physical examination, and the interpretation of CT or MR imaging studies. The diagnosis of VKDB was based on pretreatment coagulation studies (prothrombin time [PT] and partial thromboplastin time [PTT]), which are grossly abnormal, together with a normal platelet count and correction of coagulation results to normal after vitamin K administration. The mean age (± SD) at onset of symptoms was 20.4 ± 4.9 days. Two neonates (6.25%) had early VKDB, 7 (21.9%) had classic VKDB, and 23 (71.9%) had late VKDB. The most common neurological manifestations included focal seizures, disturbed consciousness level, and tense anterior fontanel. The most common general manifestations included pallor, respiratory distress, and bleeding from other sites. Radiological findings varied from acute subdural hemorrhage (SDH) in 18 cases (56.3%), intracerebral hemorrhage in 10 (31.3%), and acute SDH with underlying intracerebral hemorrhage, intraventricular hemorrhage, and/or subarachnoid hemorrhage in 4 (12.5%). Before administration of vitamin K

The old and the new in prekallikrein deficiency: historical context and a family from Argentina with PK deficiency due to a new mutation (Arg541Gln) in exon 14 associated with a common polymorphysm (Asn124Ser) in exon 5.

Science.gov (United States)

Girolami, Antonio; Vidal, Josè; Sabagh, Marcela; Salagh, Marcela; Gervan, Nora; Parody, Maria; Peroni, Edoardo; Sambado, Luisa; Guglielmone, Hugo

2014-07-01

Prekallikrein (PK) is one of the clotting factors involved in the contact phase of blood. PK has an important historical role as its deficiency state represents the second instance of a clotting defect without bleeding manifestations, the first one being factor XII deficiency. PK deficiency is a rare clotting disorder. Moreover, only 11 patients have been investigated so far by molecular biology techniques. In this article, we briefly review some of the history around PK and also present some recent data on a newly identified family from Argentina suffering from PK deficiency. Two patients are homozygous whereas other family members are heterozygous. PK activity and antigen are 1% of normal in the homozygotes and around 60 to 70% of normal in the heterozygotes. As expected, all patients are asymptomatic of bleeding or thrombosis presentations. However, the two homozygotes showed essential hypertension. The PK deficiency in this family is due to a new mutation (Arg541Gln) in exon 14. The defect segregates together with a known polymorphism, Asn124Ser, in exon 5. The significance of the presence of hypertension in the two homozygotes is discussed in view of the extra coagulation effects of PK on vasodilation, vessel permeability, and the control of blood pressure. Structure function analysis indicates that the substitution of Arg with Gln probably impedes the transmembrane diffusion of the molecule, which therefore cannot be secreted in the homozygotes. The presence of hypertension in patients with PK deficiency has been previously reported in some but not all patients. Future research activities will probably concentrate on the effect of PK and other contact phase factors on the vascular system. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of Nonclassic 11-Hydroxylase Deficiency with Ashwagandha Root

Directory of Open Access Journals (Sweden)

Daniel Powell

2017-01-01

Full Text Available An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3-β-ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.

Synthetic α subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

International Nuclear Information System (INIS)

McCormick, D.J.; Griesmann, G.E.; Huang, Z.; Lennon, V.A.

1986-01-01

A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) α subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 μg of peptide (T α 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR α subunit. Peptide H α 125-147 differs from T α 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodies to Torpedo AChR bound 125 I-labelled Hα 125-147 antibody bound Hα 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither Hα 125-147 nor T α 125-147. Rats immunized with H α 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR α subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man

26 CFR 55.6161-1 - Extension of time for paying tax or deficiency.

Science.gov (United States)

2010-04-01

... payment of the deficiency, as shown on the notice and demand. In exceptional cases, a further extension... deficiency shall be granted if the deficiency is due to negligence, to intentional disregard of rules and...

Late-onset form of beta-electron transfer flavoprotein deficiency

DEFF Research Database (Denmark)

Curcoy, A; Olsen, Rikke Katrine Jentoft; Ribes, A

2003-01-01

Multiple acyl-CoA-dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) are a group of metabolic disorders due to deficiency of either electron transfer flavoprotein (ETF) or electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO). We report the clinical features...... and biochemical and molecular genetic analyses of a patient with a mild late-onset form of GAII due to beta-ETF deficiency. Biochemical data showed an abnormal urine organic acid profile, low levels of free carnitine, increased levels of C(10:1n-6), and C(14:1n-9) in plasma, and decreased oxidation of [9,10-3H......]palmitate and [9,10-3H]myristate in fibroblasts, suggesting MAD deficiency. In agreement with these findings, mutational analysis of the ETF/ETFDH genes demonstrated an ETFB missense mutation 124T>C in exon 2 leading to replacement of cysteine-42 with arginine (C42R), and a 604_606AAG deletion in exon 6...

Storage Pool Deficiencies

Science.gov (United States)

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Synthetic. cap alpha. subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

Energy Technology Data Exchange (ETDEWEB)

McCormick, D.J.; Griesmann, G.E.; Huang, Z.; Lennon, V.A.

1986-03-05

A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) ..cap alpha.. subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 ..mu..g of peptide (T ..cap alpha.. 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR ..cap alpha.. subunit. Peptide H ..cap alpha.. 125-147 differs from T ..cap alpha.. 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodies to Torpedo AChR bound /sup 125/I-labelled H..cap alpha.. 125-147 antibody bound H..cap alpha.. 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither H..cap alpha.. 125-147 nor T ..cap alpha.. 125-147. Rats immunized with H ..cap alpha.. 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR ..cap alpha.. subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man.

Intracranial hemorrhage in infants due to vitamin K deficiency with special reference to the prognostic evaluation by CT and follow-up study

International Nuclear Information System (INIS)

Hirata, Yoshifumi; Matsukado, Yasuhiko; Kaku, Motoyuki

1982-01-01

The authors reported sixteen cases with intracranial hemorrhage due to Vitamin K deficiency and their follow-up studies. Intracranial hemorrhages were classified into four groups according to the CT findings. Eight cases were with hemorrhage of single location, whereas combined multiple hemorrhages were seen in also eight cases; four acute subdural hematomas (Group A), and four subarachnoid or intraventricular hemorrhages (Group B), four acute subdural and subarachnoid hemorrhages (Group C), and four combined intracerebral hemorrhages (Group D). Clinical symptoms were almost identical in any group. Beside CT classification of hemorrhage it was characteristic to see extensive edema in the ipsilateral hemisphere. Follow-up studies were performed in fifteen children whose age ranged from nine months to five years old. In follow-up CT, ventricular dilatation was most frequently encountered in 53%, and cortical atrophy in 33%, leukomalacia in 27%. Chronic subdural hematomas and porencephaly were also seen. In the examination of mental development (Tsumori-Inage's). normal DQ were seen in 40%, and slight or severe mental disturbance were of 40%. In conclusion, the patients of Group A and B showed good recovery and normal development, although marked cortical atrophy and ventricular dilatation were noted on follow-up CT, in which follow-up study in longer period should be indicated. In Group C and D, three cases showed severe mental disturbance and had leukomalacia on CT due to respiratory disturbance. Combined multiple hemorrhage in Vitamin K deficiency should be particularly emphasized as one of the poorest prognostic factors in mental development. (author)

Ensuring effective prevention of iodine-deficiency disorders

DEFF Research Database (Denmark)

Völzke, Henry; Caron, Philippe Jean; Dahl, Lisbeth

2016-01-01

BACKGROUND: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies...... by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. CONCLUSION: Monitoring studies can be optimized by including...... in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds....

Acute activation, desensitization and smoldering activation of human acetylcholine receptors.

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Barbara G Campling

Full Text Available The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β22β2 and (α4β22α4. The (α4β22β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β22α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

Visual loss and optic nerve head swelling in thiamine deficiency without prolonged dietary deficiency

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Gratton SM

2014-05-01

Full Text Available Sean M Gratton, Byron L LamBascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USAAbstract: Visual loss due to optic neuropathy is a rare manifestation of thiamine deficiency. We report a case of a 39-year-old woman with a body mass index (BMI of 29 kg/m2 who developed visual loss and bilateral optic nerve head swelling after a short, self-limited gastrointestinal illness. She was disoriented and inattentive and had absent ankle jerk reflexes, diminished sensation in both legs below the knees, and marked truncal ataxia. Magnetic resonance imaging (MRI showed increased T2-signal in the medial thalami and mammillary bodies. The serum thiamine level was 8 nmol/L (normal 8–30. The diagnosis of thiamine deficiency was made, and the patient’s vision and neurologic symptoms improved significantly with intramuscular thiamine treatment. Thiamine deficiency can occur in the absence of an obvious predisposing factor such as alcoholism or low body weight. The clinician must be aware of the factors that govern vitamin availability and maintain a high index of suspicion to make the diagnosis in such cases.Keywords: optic neuropathy, nutritional deficiency

The chlorophyll-deficient golden leaf mutation in cucumber is due to a single nucleotide substitution in CsChlI for magnesium chelatase I subunit.

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Gao, Meiling; Hu, Liangliang; Li, Yuhong; Weng, Yiqun

2016-10-01

The cucumber chlorophyll-deficient golden leaf mutation is due to a single nucleotide substitution in the CsChlI gene for magnesium chelatase I subunit which plays important roles in the chlorophyll biosynthesis pathway. The Mg-chelatase catalyzes the insertion of Mg(2+) into the protoporphyrin IX in the chlorophyll biosynthesis pathway, which is a protein complex encompassing three subunits CHLI, CHLD, and CHLH. Chlorophyll-deficient mutations in genes encoding the three subunits have played important roles in understanding the structure, function and regulation of this important enzyme. In an EMS mutagenesis population, we identified a chlorophyll-deficient mutant C528 with golden leaf color throughout its development which was viable and able to set fruits and seeds. Segregation analysis in multiple populations indicated that this leaf color mutation was recessively inherited and the green color showed complete dominance over golden color. Map-based cloning identified CsChlI as the candidate gene for this mutation which encoded the CHLI subunit of cucumber Mg-chelatase. The 1757-bp CsChlI gene had three exons and a single nucleotide change (G to A) in its third exon resulted in an amino acid substitution (G269R) and the golden leaf color in C528. This mutation occurred in the highly conserved nucleotide-binding domain of the CHLI protein in which chlorophyll-deficient mutations have been frequently identified. The mutant phenotype, CsChlI expression pattern and the mutated residue in the CHLI protein suggested the mutant allele in C528 is unique among mutations identified so far in different species. This golden leaf mutant not only has its potential in cucumber breeding, but also provides a useful tool in understanding the CHLI function and its regulation in the chlorophyll biosynthesis pathway as well as chloroplast development.

MRI findings of complete growth hormone deficiency

International Nuclear Information System (INIS)

Ichiba, Yozo

1995-01-01

Magnetic resonance (MR) imaging was performed on the pituitary gland of 20 children (age range, 2-11 years) with short stature due to growth hormone deficiency. Sixteen patients with multiple pituitary hormone deficiency showed disappearance of the pituitary stalk, disappearance of high signal area of the posterior pituitary, presence of ectopic pituitary, and decreased volume of the anterior pituitary. Many of them had a history of perinatal abnormalities such as asphyxia at delivery, breech delivery, and bradytocia. On the contrary, patients with isolated growth hormone deficiency presented no abnormal findings on MR images, and had no history of perinatal abnormalities. The findings of pituitary stalk separation syndrome suggested the presence of multiple hypopituitarism. (S.Y.)

MRI findings of complete growth hormone deficiency

Energy Technology Data Exchange (ETDEWEB)

Ichiba, Yozo [National Hospital of Okayama (Japan)

1995-10-01

Magnetic resonance (MR) imaging was performed on the pituitary gland of 20 children (age range, 2-11 years) with short stature due to growth hormone deficiency. Sixteen patients with multiple pituitary hormone deficiency showed disappearance of the pituitary stalk, disappearance of high signal area of the posterior pituitary, presence of ectopic pituitary, and decreased volume of the anterior pituitary. Many of them had a history of perinatal abnormalities such as asphyxia at delivery, breech delivery, and bradytocia. On the contrary, patients with isolated growth hormone deficiency presented no abnormal findings on MR images, and had no history of perinatal abnormalities. The findings of pituitary stalk separation syndrome suggested the presence of multiple hypopituitarism. (S.Y.).

The Short-term Therapeutic Effect of the Three-part Massotherapy for Insomnia Due to Deficiency of Both the Heart and the Spleen- A Report of 100 Cases

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Objective: To evaluate the short-term therapeutic effect of the three-part massotherapy on insomnia due to deficiency of both the heart and spleen. Methods: Two hundred cases were randomly divided into a treatment group and a control group, each consisting of 100 cases. Patients in the treatment group were treated with the three-part massotherapy, while those in the control group with oral administration of Guipi Wan (归脾丸Pill for Invigorating the Spleen and Nourishing the Heart). The total clinical therapeutic effects, the total scores of Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) of the treatment group were compared with those of the control group. Results: After the treatment, the total therapeutic effects, PSQI, SAS, and SDS of the two groups all showed significant improvement (P<0.01), and the scores of the treatment group were superior to those of the control group (P<0.01). Conclusion: The three-part massotherapy has definite therapeutic effects on insomnia due to deficiency of both the heart and the spleen, which is safe and easy to operate, and worthy of popularization.

Prevalence of Iron Deficiency and Iron Deficiency Anemia in High-School Girl Students of Yazd

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M Noori Shadkam

2009-07-01

Full Text Available Introduction: It is generally assumed that 50% of the cases of anemia are due to iron deficiency. The most severe consequence of iron depletion is iron deficiency anemia (IDA, and it is still considered the most common nutrition deficiency worldwide. The main risk factors for IDA include: inadequate iron intake, impaired absorption or transport, physiologic losses associated with chronological or reproductive age, or acute or chronic blood loss, parasite infections such as hookworms, acute and chronic infections, including malaria, cancer, tuberculosis, HIV and other micronutrient deficiencies, including vitamins A and B12, folate, riboflavin, and copper deficiency. Methods: This work as a cross-sectional study was done in 2007-2008 in Yazd. Two hundred girls who participated in the study were selected randomly from eight girl high schools. Five ml venous blood was collected for determination of serum ferritin and cell blood count (CBC. Serum ferritin was determined by using ECLIA method and CBC by cell counter SYSMEX KX21N. Iron deficiency was defined as having serum ferritin values below 12 μ/l. Anemia was defined as having Hemoglobin levels below12 g/dl. Iron-deficiency anemia was considered to be the combination of both. Results: The3 mean ageyears and body mass index (kg/m2 were 15.19±0.7years and 21.5±4.2, respectively. Distribution in the 14, 15 and 16 years and more age groups were 13, 58.5 and 28.5 percent, respectively. Mean of Hemoglobin(g/dl, Hematocrit(%, MCV (fl, MCH (pg, MCHC (g/dl and ferritin(μ/l were 12.8±0.9, 38.9±3.0, 80.7±4.3, 26.6±1.8, 33.2±3.6 and 23±18.2, respectively. Of the total, 13.5% were anemic, 68% of which had Iron Deficiency Anemia (9.3% of the total. Iron deficiency was present in 34.7% of the population under study. Conclusion: According to world health organization criteria, anemia is a mild public health problem in this region, but iron deficiency is a significant problem and suitable measures for

Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency.

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Ozen, S; Aldemir, O

2012-01-01

The patient is a 2.8 years old male who is extremely obese and severe hyperphagic from birth. He had seizures attacks and apnea from the second week of his life. He has red hair and serum cortisol and ACTH levels are very low. We examined our patient as a hypocortisolism due to ACTH deficiency and central hypothyrodism. After the corticosteroid replacement therapy hair color changed to brown. We performed molecular genetic analysis at the Institue for Experimental Pediatric Endocrinology laboratory in Berlin, Germany by Krude H. and found compound heterozygous mutations. As a result the case is diagnosed as POMC deficiency.

Maternal vitamin D deficiency associated with neonatal hypocalcaemic convulsions

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Tibbott Rebecca

2007-09-01

Full Text Available Abstract Maternal vitamin D insufficiency is not uncommon. Infants born to mothers who are deficient in vitamin D and or calcium, usually due to cultural modifications in their diets or clothing habits, and in addition are breastfed, are at risk of developing vitamin D deficiency and hypocalcaemia. We present a case of neonatal hypocalcaemic seizures secondary to vitamin D deficiency. Rickets in children resulting from vitamin D deficiency is well documented. It is also becoming clear that there is a positive correlation between maternal vitamin D status during pregnancy and lactation and the development of rickets both in infancy and childhood. The correlation between maternal vitamin D, neonatal vitamin D and hypocalcaemia is not well documented.

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

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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.

Iodine Deficiency

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... Fax/Phone Home » Iodine Deficiency Leer en Español Iodine Deficiency Iodine is an element that is needed ... world’s population remains at risk for iodine deficiency. Iodine Deficiency FAQs WHAT IS THE THYROID GLAND? The ...

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

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Uppal, Surabhi; Jee, Youn Hee; Lightbourne, Marissa; Han, Joan C; Stratakis, Constantine A

2017-01-01

Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella. The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC. We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.

The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters

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Madhavan Raghavan

2008-07-01

Full Text Available Abstract Background A crucial event in the development of the vertebrate neuromuscular junction (NMJ is the postsynaptic enrichment of muscle acetylcholine (ACh receptors (AChRs. This process involves two distinct steps: the local clustering of AChRs at synapses, which depends on the activation of the muscle-specific receptor tyrosine kinase MuSK by neural agrin, and the global dispersal of aneural or "pre-patterned" AChR aggregates, which is triggered by ACh or by synaptogenic stimuli. We and others have previously shown that tyrosine phosphatases, such as the SH2 domain-containing phosphatase Shp2, regulate AChR cluster formation in muscle cells, and that tyrosine phosphatases also mediate the dispersal of pre-patterned AChR clusters by synaptogenic stimuli, although the specific phosphatases involved in this latter step remain unknown. Results Using an assay system that allows AChR cluster assembly and disassembly to be studied separately and quantitatively, we describe a previously unrecognized role of the tyrosine phosphatase Shp2 in AChR cluster disassembly. Shp2 was robustly expressed in embryonic Xenopus muscle in vivo and in cultured myotomal muscle cells, and treatment of the muscle cultures with an inhibitor of Shp2 (NSC-87877 blocked the dispersal of pre-patterned AChR clusters by synaptogenic stimuli. In contrast, over-expression in muscle cells of either wild-type or constitutively active Shp2 accelerated cluster dispersal. Significantly, forced expression in muscle of the Shp2-activator SIRPα1 (signal regulatory protein α1 also enhanced the disassembly of AChR clusters, whereas the expression of a truncated SIRPα1 mutant that suppresses Shp2 signaling inhibited cluster disassembly. Conclusion Our results suggest that Shp2 activation by synaptogenic stimuli, through signaling intermediates such as SIRPα1, promotes the dispersal of pre-patterned AChR clusters to facilitate the selective accumulation of AChRs at developing NMJs.

Carbohydrate production and transport in cotton cultivars grown under boron deficiency

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Julio Cesar Bogiani

2013-12-01

Full Text Available An adequate supply of boron (B is required for the optimal growth and development of cotton (Gossypium hirsutum L. plants, but the low phloem mobility of B limits the possibilities of correcting B deficiency. There are indications that different cotton cultivars could have different responses to B deficiency. The differences in responses of cotton cultivars to B regarding photoassimilate production and transport were studied in a greenhouse experiment with nutrient solution. Treatments consisted of three cotton cultivars (FMT 701, DP 604BG and FMX 993 and five concentrations of B (0.0, 2.5, 5.0, 10.0 and 20.0 µmol L−1. Sampling began at the phenological stage B1 (first square and continued for four weeks. The leaf area and the number of reproductive branches and structures decreased due to B deficiency. A higher level of abortion of reproductive structures was observed under B deficiency. Boron deficiency increased the internal CO2 concentration but decreased the transpiration rate, stomatal conductance and photosynthesis. Despite the decrease in photosynthesis, nonstructural carbohydrates accumulated in the leaves due to decreased export to bolls in B-deficient plants. The response to B deficiency is similar among cotton cultivars, which shows that the variability for this trait is low even for cultivars with different genetic backgrounds.

Cost-benefit analysis of hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency: for consideration of expanded newborn screening in Hong Kong.

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Lee, Hencher Han-Chih; Mak, Chloe Miu; Poon, Grace Wing-Kit; Wong, Kar-Yin; Lam, Ching-Wan

2014-06-01

To evaluate the cost-benefit of implementing an expanded newborn screening programme for hyperphenylalaninemias due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency in Hong Kong. Regional public hospitals in Hong Kong providing care for cases of inborn errors of metabolism. Implementational and operational costs of a new expanded mass spectrometry-based newborn screening programme were estimated. Data on various medical expenditures for the mild and severe phenotypic subtypes were gathered from a case cohort diagnosed with PTPS deficiency from 2001 to 2009. Local incidence from a previously published study was used. Implementation and operational costs of an expanded newborn screening programme in Hong Kong were estimated at HKD 10,473,848 (USD 1,342,801) annually. Assuming a birthrate of 50,000 per year and an incidence of 1 in 29,542 live births, the medical costs and adjusted loss of workforce per year would be HKD 20,773,207 (USD 2,663,232). Overall the annual savings from implementing the programme would be HKD 9,632,750 (USD 1,234,968). Our estimates show that implementation of an expanded newborn screening programme in Hong Kong is cost-effective, with a significant annual saving for public expenditure. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

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Losen, Mario; Martinez-Martinez, Pilar; Molenaar, Peter C.; Lazaridis, Konstantinos; Tzartos, Socrates; Brenner, Talma; Duan, Rui-Sheng; Luo, Jie; Lindstrom, Jon; Kusner, Linda

2015-01-01

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice. PMID:25796590

Diagnostic Error of a Patient with Combined Inherited Factor VII and Factor X Deficiency due to Accidental Ingestion of a Diphacinone Rodenticide.

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Li, Min; Jin, Yanhui; Wang, Mingshan; Xie, Yaosheng; Ding, Hongxiang

2016-11-01

To explore the characteristics of laboratory examination and confirm the diagnosis of a patient with combined inherited FVII and FX deficiency after he ingested diphacinone rodenticide accidentally. The coagulant parameter screening tests and coagulation factor activities were tested many times in the patient due to accidental ingestion of a diphacinone rodenticide. After the patient was treated for more than one year, gene analysis of correlated coagulation factors was analyzed in the patient and other family members by DNA direct sequencing. 106 persons were selected as controls from routine health examinations. After the patient was admitted to hospital, routine coagulation screening tests revealed the prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) and low levels of vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) activity, which was 102.4 seconds, 88.5 seconds, 7%, 3%, 8%, and 2%, respectively. During more than one year of treatment, the value of PT and APTT still showed significantly prolonged activity and FVII and FX activity levels were about 5%. While FII and FIX activity levels were in the normal range after 12 weeks of treatment. Two homozygous mutations, g.11267C>T of F7 gene resulting in the substitution Arg277Cys and g.28139G>T of F10 gene leading to the substitution Val384Phe, were identified in the patient. The patient's parents and sister was heterozygous for Arg277Cys and Val384Phe mutations. FVII and FX antigen levels in the patient were 7% and 30%, respectively. There were many similarities in the characteristics of laboratory examination between combined inherited FVII and FX deficiency and acquired vitamin K deficiency. The best way to identify them was gene analysis.

Electron transfer flavoprotein deficiency: Functional and molecular aspects

DEFF Research Database (Denmark)

Schiff, M; Froissart, R; Olsen, Rikke Katrine Jentoft

2006-01-01

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a recessively inherited metabolic disorder that can be due to a deficiency of electron transfer flavoprotein (ETF) or its dehydrogenase (ETF-ubiquinone oxidoreductase). ETF is a mitochondrial matrix protein consisting of alpha- (30kDa) and beta......- (28kDa) subunits encoded by the ETFA and ETFB genes, respectively. In the present study, we have analysed tissue samples from 16 unrelated patients with ETF deficiency, and we report the results of ETF activity, Western blot analysis and mutation analysis. The ETF assay provides a reliable diagnostic...... tool to confirm ETF deficiency in patients suspected to suffer from MADD. Activity ranged from less than 1 to 16% of controls with the most severely affected patients disclosing the lowest activity values. The majority of patients had mutations in the ETFA gene while only two of them harboured...

Iron-Deficiency Anemia

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Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

Minimising radiation exposure due to source assembly-related deficiencies in industrial gamma radiography exposure devices (IGREDs)

International Nuclear Information System (INIS)

Sivaraman, G.; Kannan, R.; Nandakumar, A.N.; Subrahmanya, M.J.; Murthy, B.K.S.

2000-01-01

Industrial radiographers receive higher doses as compared to radiation workers in medicine, agriculture, research, etc. Hence, it is essential that industrial gamma radiography exposure device (IGRED) be provided with efficient and effective safety systems in their design and operation to ensure smooth operation and minimise radiation exposures to the operators and public. Even though all these exposure devices have undergone stringent tests for radiographic exposure devices under international or national standards, certain deficiencies were noticed when scientists of Radiological Physics and Advisory Division (RPAD), carried out radiography equipment inspection of IGREDs. Some examples are briefly described here. The use of depleted Uranium pencil in some models led to the source pencil getting jammed due to formation of Uranium Oxide and bulging of the pencil. The solution was to replace the uranium pencil with high quality tungsten pencils or stainless steel clad pencils. In one type of pencils the source assembly would flare up after some use obstructing the smooth movement of the source assembly. The suggestion to subject the source assemblies to heat treatment solved the problem. In another type, the source pencil was getting corroded in high humid condition and affected the source movement. When the composition of the source pencil was changed it could withstand high humid condition. Another model had a hook type coupling between source assembly and drive cable. This often resulted in disengagement of the source assembly from the drive cable. Suggestions were made to change the coupling to ball and socket coupling for smooth functioning and for 'fail-safe' operation. During early days of the use of remote operated IGRED, in one particular model of the IGRED, the Iridium source wafers were directly loaded in a single encapsulation. Once the welding gave way and the source wafers got strewn. Subsequently, the source pellets/wafers were doubly encapsulated

Recent advances in biochemical and molecular analysis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

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Jin-Ho Choi

2016-03-01

Full Text Available The term congenital adrenal hyperplasia (CAH covers a group of autosomal recessive disorders caused by defects in one of the steroidogenic enzymes involved in the synthesis of cortisol or aldosterone from cholesterol in the adrenal glands. Approximately 95% of all CAH cases are caused by 21-hydroxylase deficiency encoded by the CYP21A2 gene. The disorder is categorized into classical forms, including the salt-wasting and the simple virilizing types, and nonclassical forms based on the severity of the disease. The severity of the clinical features varies according to the level of residual 21-hydroxylase activity. Newborn screening for CAH is performed in many countries to prevent salt-wasting crises in the neonatal period, to prevent male sex assignment in affected females, and to reduce long-term morbidities, such as short stature, gender confusion, and psychosexual disturbances. 17α-hydroxyprogesterone is a marker for 21-hydroxylase deficiency and is measured using a radioimmunoassay, an enzyme-linked immunosorbent assay, or a fluoroimmunoassay. Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes. Urinary steroid analysis by gas chromatography mass spectrometry also provides qualitative and quantitative data on the excretion of steroid hormone metabolites. Molecular analysis of CYP21A2 is useful for genetic counseling, confirming diagnosis, and predicting prognoses. In conclusion, early detection using neonatal screening tests and treatment can prevent the worst outcomes of 21-hydroxylase deficiency.

The formation of acetylcholine receptor clusters visualized with quantum dots

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Peng H Benjamin

2009-07-01

Full Text Available Abstract Background Motor innervation of skeletal muscle leads to the assembly of acetylcholine receptor (AChR clusters in the postsynaptic membrane at the vertebrate neuromuscular junction (NMJ. Synaptic AChR aggregation, according to the diffusion-mediated trapping hypothesis, involves the establishment of a postsynaptic scaffold that "traps" freely diffusing receptors into forming high-density clusters. Although this hypothesis is widely cited to explain the formation of postsynaptic AChR clusters, direct evidence at molecular level is lacking. Results Using quantum dots (QDs and live cell imaging, we provide new measurements supporting the diffusion-trap hypothesis as applied to AChR cluster formation. Consistent with published works, experiments on cultured Xenopus myotomal muscle cells revealed that AChRs at clusters that formed spontaneously (pre-patterned clusters, also called hot spots and at those induced by nerve-innervation or by growth factor-coated latex beads were very stable whereas diffuse receptors outside these regions were mobile. Moreover, despite the restriction of AChR movement at sites of synaptogenic stimulation, individual receptors away from these domains continued to exhibit free diffusion, indicating that AChR clustering at NMJ does not involve an active attraction of receptors but is passive and diffusion-driven. Conclusion Single-molecular tracking using QDs has provided direct evidence that the clustering of AChRs in muscle cells in response to synaptogenic stimuli is achieved by two distinct cellular processes: the Brownian motion of receptors in the membrane and their trapping and immobilization at the synaptic specialization. This study also provides a clearer picture of the "trap" that it is not a uniformly sticky area but consists of discrete foci at which AChRs are immobilized.

Iron-Deficiency Anemia

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... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

Protection against high-fat diet-induced obesity in Helz2-deficient male mice due to enhanced expression of hepatic leptin receptor.

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Yoshino, Satoshi; Satoh, Tetsurou; Yamada, Masanobu; Hashimoto, Koshi; Tomaru, Takuya; Katano-Toki, Akiko; Kakizaki, Satoru; Okada, Shuichi; Shimizu, Hiroyuki; Ozawa, Atsushi; Tuchiya, Takafumi; Ikota, Hayato; Nakazato, Yoichi; Mori, Munemasa; Matozaki, Takashi; Sasaki, Tsutomu; Kitamura, Tadahiro; Mori, Masatomo

2014-09-01

Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor γ in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db/db mice lacking functional Leprb did not. Fatty acid-β oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for

LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

Directory of Open Access Journals (Sweden)

I.A. Meijer

2015-12-01

Full Text Available Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4 years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu461SerfsX47, and complete uniparental isodisomy of maternal chromosome 2. This mutation is predicted to cause complete lipin-1 deficiency. The patient had six rhabdomyolytic crises, with creatine kinase (CK levels up to 300,000 U/L (normal, 30 to 200. Plasma CK remained elevated between crises. A treatment protocol was instituted, with early aggressive monitoring, hydration, electrolyte replacement and high caloric, high carbohydrate intake. The patient received dexamethasone during two crises, which was well-tolerated and in these episodes, peak CK values were lower than in preceding episodes. Studies of anti-inflammatory therapy may be indicated in lipin-1 deficiency.

β-Galactosidase Deficiency in Colombia

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Alfredo Uribe PhD

2015-05-01

Full Text Available β-Galactosidase (BGal is the first enzyme involved in the catabolism of sphingolipids. Two pathologies have been directly associated with its deficiency: GM1 gangliosidosis and Morquio B. Morquio B is among the rarest types of mucopolysaccharidosis (MPS. We aim to document the β-galactosidase deficiency in Colombia. We evaluated leukocytes from 1492 healthy Colombian individuals and 923 patients, referred between 2005 and August 2014. Dried blood spot (DBS samples from the same number of patients were evaluated. β-Galactosidase was measured with 4-methylumbelliferyl-β- d -galactoside. As a control enzyme, the total hexosaminidase activity was also evaluated. We identified 14 patients with GM1 gangliosidosis, 5 patients with Morquio B, and 1 patient with I-cell disease. We could establish a reference value for Bgal in Colombian leukocyte samples. GM1 gangliosidosis is the main pathology associated with a direct deficiency of BGal. The high number of patients found with MPS IVB indicates that there are patients who could be misdiagnosed due to an unawareness of the disease.

CALCIUM DEFICIENCY AND CAUSATION OF RICKETS IN ...

African Journals Online (AJOL)

hi-tech

2005-03-03

Mar 3, 2005 ... communication about the benefits of exposing children to sunlight is very important in preventing the ... of rickets was nutritional deficiency of vitamin D due either to ..... resulting from less time being spent outdoors is the cause.

Genetics Home Reference: adenosine deaminase deficiency

Science.gov (United States)

... Combined Immunodeficiency (SCID) and Conditions Associated with T Cell Lymphoneia (PDF) Genetic Testing (1 link) Genetic Testing Registry: Severe ... Diseases Immune Deficiency Foundation Jeffrey Modell Foundation National Organization for Rare ... OMIM (1 link) SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE ...

Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients

International Nuclear Information System (INIS)

Alangari, Abdullah; AlHarbi, Abdullah; AlGhonaium Abdulaziz; Santisteban, Ines; Hershfield, Michael

2009-01-01

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients with an Arabic ethnic background. We report on two Saudi girls with PNP deficiency. Both showed severe lymphopenia and neurological involvement. Sequencing of the PNP gene of one girl revealed a novel missense mutation Pro146>Leu in exon 4 due to a change in the codon from CCT>CTT. Expression of PNP (146L) cDNA in E coli indicated that the mutation greatly reduced, but did not completely eliminate PNP activity. (author)

Mechanism of acetylcholine receptor cluster formation induced by DC electric field.

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Hailong Luke Zhang

Full Text Available BACKGROUND: The formation of acetylcholine receptor (AChR cluster is a key event during the development of the neuromuscular junction. It is induced through the activation of muscle-specific kinase (MuSK by the heparan-sulfate proteoglycan agrin released from the motor axon. On the other hand, DC electric field, a non-neuronal stimulus, is also highly effective in causing AChRs to cluster along the cathode-facing edge of muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: To understand its molecular mechanism, quantum dots (QDs were used to follow the movement of AChRs as they became clustered under the influence of electric field. From analyses of trajectories of AChR movement in the membrane, it was concluded that diffuse receptors underwent Brownian motion until they were immobilized at sites of cluster formation. This supports the diffusion-mediated trapping model in explaining AChR clustering under the influence of this stimulus. Disrupting F-actin cytoskeleton assembly and interfering with rapsyn-AChR interaction suppressed this phenomenon, suggesting that these are integral components of the trapping mechanism induced by the electric field. Consistent with the idea that signaling pathways are activated by this stimulus, the localization of tyrosine-phosphorylated forms of AChR β-subunit and Src was observed at cathodal AChR clusters. Furthermore, disrupting MuSK activity through the expression of a kinase-dead form of this enzyme abolished electric field-induced AChR clustering. CONCLUSIONS: These results suggest that DC electric field as a physical stimulus elicits molecular reactions in muscle cells in the form of cathodal MuSK activation in a ligand-free manner to trigger a signaling pathway that leads to cytoskeletal assembly and AChR clustering.

Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

Institute of Scientific and Technical Information of China (English)

Qi-Guang Shi; Zhi-Hong Wang; Xiao-Wei Ma; Da-Qi Zhang; Chun-Sheng Yang; Fu-Dong Shi; Li Yang

2012-01-01

Objective To evaluate the frequency,distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor (AChR) in patients with myasthenia gravis (MG).Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG (OMG) (n =90) and generalized MG (GMG) patients (n =110).The fetaltype (2α∶ β∶ γ∶ δ) and adult-type (2α∶ β∶ ε∶ δ) AChR were used as antigens,and their relevance to disease presentation was assessed.Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined,with 14 having serum specific to the AChR-γ subunit,and 22 to the AChR-ε subunit.The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only (P =0.015).Compared with OMG patients,the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG.Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio (OR),1.03;95％ confidence interval (CI),1.01-1.06 and OR,5.09;95％ CI,2.23-11.62].Conclusion Using both fetal-and adulttype AChRs as the antigens may be more sensitive than using either subtype.Patients with serum specific to both isoforms are at a greater risk of progressing to GMG.Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

Epidemiology of SHOX deficiency.

Science.gov (United States)

Nicolosi, A; Caruso-Nicoletti, M

2010-06-01

Deletion of short stature homeobox-containing (SHOX) gene, in the pseudoautosomal region (PAR1) of X and Y chromosomes, is an important cause of short stature. Homozygous loss of SHOX results in the more severe Langer mesomelic dysplasia, while SHOX haploinsufficiency cause a wide spectrum of short stature phenotypes, including patients with Turner syndrome, Leri Weill dyschondrosteosis (LWD), and idiopathic short stature (ISS). In Turner syndrome, haploinsufficiency of SHOX gene, as well as short stature, are present in 100%; nevertheless, SHOX deficiency accounts for only two-thirds of Turner patients' short stature. In LWD the prevalence of SHOX gene anomalies varies from 56% to 100%. This wide range might be due to different factors such as selection criteria of patients, sample size, and method used for screening SHOX mutations. The real challenge is to establish the prevalence of SHOX deficiency in ISS children given that published studies have reported this association with a very broad frequency range varying from 1.5% to 15%. An important variable in these studies is represented by the method used for screening SHOX mutations and sometimes by differences in patient selection. Short stature is present by definition in 3 out of 100 subjects; if we consider a frequency of SHOX defects of 3% among ISS, we should expect a population prevalence of 1 in 1000. This prevalence would be higher than that of GH deficiency (1:3,500) and of Turner syndrome (1:2,500 females), suggesting that SHOX deficiency could be one of the most frequent monogenetic causes of short stature.

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

NARCIS (Netherlands)

Zimmermann, M.B.

2008-01-01

Iodine deficiency has multiple adverse effects on growth and development due to inadequate thyroid hormone production that are termed the iodine deficiency disorders (IDD). IDD remains the most common cause of preventable mental impairment worldwide. IDD assessment methods include urinary iodine

Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

DEFF Research Database (Denmark)

Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet

2015-01-01

Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement...... available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library......, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia...

Proposed Model of Predicting the Reduced Yield Axial Load of Reinforced Concrete Columns Due to Casting Deficiency Effect

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Achillopoulou Dimitra

2014-12-01

Full Text Available The study deals with the investigation of the effect of casting deficiencies- both experimentally and analytically on axial yield load or reinforced concrete columns. It includes 6 specimens of square section (150x150x500 mm of 24.37 MPa nominal concrete strength with 4 longitudinal steel bars of 8 mm (500 MPa nominal strength with confinement ratio ωc=0.15. Through casting procedure the necessary provisions defined by International Standards were not applied strictly in order to create construction deficiencies. These deficiencies are quantified geometrically without the use of expensive and expertise non-destructive methods and their effect on the axial load capacity of the concrete columns is calibrated trough a novel and simplified prediction model extracted by an experimental and analytical investigation that included 6 specimens. It is concluded that: a even with suitable repair, load reduction up to 22% is the outcome of the initial construction damage presence, b the lower dispersion is noted for the section damage index proposed, c extended damage alters the failure mode to brittle accompanied with longitudinal bars buckling, d the proposed model presents more than satisfying results to the load capacity prediction of repaired columns.

Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

Science.gov (United States)

Ramsay, D A; Drachman, D B; Pestronk, A

1988-10-11

The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

Matrix Metalloproteinases in Myasthenia Gravis

NARCIS (Netherlands)

Helgeland, G.; Petzold, A.F.S.; Luckman, S.P.; Gilhus, N.E.; Plant, G.T.; Romi, F.R.

2011-01-01

Introduction: Myasthenia gravis (MG) is an autoimmune disease with weakness in striated musculature due to anti-acetylcholine receptor (AChR) antibodies or muscle specific kinase at the neuromuscular junction. A subgroup of patients has periocular symptoms only; ocular MG (OMG). Matrix

Gastric emptying in patients with vitamin B12 deficiency

International Nuclear Information System (INIS)

Yagci, Muenci; Yamac, Kadri; Acar, Kadir; Haznedar, Rauf; Cingi, Elif; Kitapci, Mehmet

2002-01-01

The clinical presentation of patients with vitamin B 12 deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B 12 deficiency. The aim of this study was to evaluate the effect of vitamin B 12 deficiency on autonomic nervous system function by studying gastric emptying times (T 1/2 ). Twenty patients with newly diagnosed vitamin B 12 deficiency and 12 control patients with gastritis and normal vitamin B 12 levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B 12 replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T 1/2 in patients before and after treatment and in controls were 103.83±48.80 min, 90.00±17.29 min and 74.55±8.52 min, respectively. The difference in mean gastric emptying T 1/2 between patients before treatment and controls was statistically significant (P 12 treatment (P 1/2 was somewhat shorter. There were no positive or negative correlations between gastric emptying T 1/2 and the following parameters: haemoglobin, vitamin B 12 level and Helicobacter pylori positivity. In conclusion, gastric emptying T 1/2 was prolonged in patients with vitamin B 12 deficiency and this prolongation was not corrected after vitamin B 12 replacement therapy. Although autonomic nervous system dysfunction due to vitamin B 12 deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon. The level of vitamin B 12 does not correlate with the degree of autonomic nervous system dysfunction measured by radionuclide gastric emptying studies. (orig.)

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

Advisory Committee on human radiation experiments. Supplemental Volume 2a, Sources and documentation appendices. Final report

International Nuclear Information System (INIS)

1995-01-01

This large document provides a catalog of the location of large numbers of reports pertaining to the charge of the Presidential Advisory Committee on Human Radiation Research and is arranged as a series of appendices. Titles of the appendices are Appendix A- Records at the Washington National Records Center Reviewed in Whole or Part by DoD Personnel or Advisory Committee Staff; Appendix B- Brief Descriptions of Records Accessions in the Advisory Committee on Human Radiation Experiments (ACHRE) Research Document Collection; Appendix C- Bibliography of Secondary Sources Used by ACHRE; Appendix D- Brief Descriptions of Human Radiation Experiments Identified by ACHRE, and Indexes; Appendix E- Documents Cited in the ACHRE Final Report and other Separately Described Materials from the ACHRE Document Collection; Appendix F- Schedule of Advisory Committee Meetings and Meeting Documentation; and Appendix G- Technology Note

Advisory Committee on human radiation experiments. Supplemental Volume 2a, Sources and documentation appendices. Final report

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-01-01

This large document provides a catalog of the location of large numbers of reports pertaining to the charge of the Presidential Advisory Committee on Human Radiation Research and is arranged as a series of appendices. Titles of the appendices are Appendix A- Records at the Washington National Records Center Reviewed in Whole or Part by DoD Personnel or Advisory Committee Staff; Appendix B- Brief Descriptions of Records Accessions in the Advisory Committee on Human Radiation Experiments (ACHRE) Research Document Collection; Appendix C- Bibliography of Secondary Sources Used by ACHRE; Appendix D- Brief Descriptions of Human Radiation Experiments Identified by ACHRE, and Indexes; Appendix E- Documents Cited in the ACHRE Final Report and other Separately Described Materials from the ACHRE Document Collection; Appendix F- Schedule of Advisory Committee Meetings and Meeting Documentation; and Appendix G- Technology Note.

Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model - recommendations for methods and experimental designs

Science.gov (United States)

Kusner, Linda L.; Losen, Mario; Vincent, Angela; Lindstrom, Jon; Tzartos, Socrates; Lazaridis, Konstantinos; Martinez-Martinez, Pilar

2015-01-01

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies. PMID:25743217

Congenital Myasthenic Syndrome in a Mixed Breed Dog

Directory of Open Access Journals (Sweden)

Theresa J. Blakey

2017-10-01

Full Text Available A 6-month-old, male, intact mixed breed dog was presented for a 3-month history of progressive generalized weakness. Neurologic examination revealed non-ambulatory tetraparesis, weakness of the head and neck, and decreased withdrawal reflexes in all limbs consistent with a generalized neuromuscular disorder. Electromyography and motor nerve conduction velocity were normal. Repetitive nerve stimulation showed a decremental response of the compound muscle action potential with improvement upon intravenous administration of edrophonium chloride. The serum acetylcholine receptor (AChR antibody titer was within reference range. Cerebrospinal fluid analysis was unremarkable. A presumptive diagnosis of post-synaptic congenital myasthenic syndrome (CMS was made. Treatment with pyridostigmine bromide was initiated with titrated increases in dosage resulting in an incomplete improvement in clinical signs. The dog was euthanized 2 months after initiation of treatment due to poor quality of life. Immunostaining for localization of antibodies against end-plate proteins in muscle biopsies was negative. Immunofluorescence staining for AChRs in external intercostal muscle biopsies showed absence of AChRs and biochemical quantitation showed a markedly decreased concentration of AChRs with no detectable AChR-bound autoantibody which confirmed the diagnosis of a CMS. Evaluation for the CHRNE mutation previously identified as the causative mutation of CMS in Jack Russell Terriers was performed and was negative. This is the first reported confirmed case of CMS in a mixed breed dog and provides a review of typical clinical and diagnostic findings as well as treatment considerations.

Zinc Deficiency in Humans and its Amelioration

Directory of Open Access Journals (Sweden)

Yashbir Singh Shivay

2015-01-01

Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

Zinc Deficiency in Humans and its Amelioration

Directory of Open Access Journals (Sweden)

Yashbir Singh Shivay

2015-12-01

Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections. Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops. The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome

Directory of Open Access Journals (Sweden)

Marie Mongin

2016-03-01

Full Text Available Background: Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. Phenomenology Shown: Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. Educational Value: Proper identification of the paroxysmal events and early diagnosis is important since the disease is potentially treatable.

Anemia and iron deficiency before and after bariatric surgery.

Science.gov (United States)

Salgado, Wilson; Modotti, Caue; Nonino, Carla Barbosa; Ceneviva, Reginaldo

2014-01-01

Iron deficiency and anemia are changes often associated with obesity. Bariatric surgery is responsible for increasing the iron loss and reducing its absorption. The objective of this study was to evaluate anemia and iron deficiency before and after bariatric surgery and to relate them to possible predisposing factors. A retrospective study was conducted on obese patients submitted to open Roux-en-Y gastric bypass, in which clinical and laboratory data were obtained up to 48 months postoperatively. Patients were divided into groups according to the presence or absence of anemia and to the presence or absence of iron deficiency (even without anemia), and all data were compared between these groups. Preoperatively, 21.5% of patients had anemia and 20% had iron deficiency. The number of patients with anemia did not vary through the 4 years of the study, but ferritin levels significantly decreased with time (Panemia. Female gender was a variable associated with a greater incidence of iron deficiency. Anemia and iron deficiency are frequent in obese patients and must be treated before surgery. Medical and nutritional surveillance is important in the postoperative period of bariatric surgery. Management of each condition must be directed at correcting the 2 major sources of iron deficiency and anemia: food intolerance (mostly meat intolerance) and losses (frequently due to menstruation). These are the factors more related to iron deficient anemia. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency

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Bret M. Evers

2017-09-01

Full Text Available Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL and Niemann-Pick type C (NPC, and is implicated in Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD-TDP with progranulin (PGRN deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Using an unbiased lipidomic approach, we found that brain lipid composition in humans and mice with PGRN deficiency shows disease-specific differences that distinguish them from normal and other pathologic groups. PGRN loss leads to an accumulation of polyunsaturated triacylglycerides, as well as a reduction of diacylglycerides and phosphatidylserines in fibroblast and enriched lysosome lipidomes. Transcriptomic analysis of PGRN-deficient mouse brains revealed distinct expression patterns of lysosomal, immune-related, and lipid metabolic genes. These findings have implications for the pathogenesis of FTLD-TDP due to PGRN deficiency and suggest lysosomal dysfunction as an underlying mechanism.

ATP Synthase Deficiency due to TMEM70 Mutation Leads to Ultrastructural Mitochondrial Degeneration and Is Amenable to Treatment

Directory of Open Access Journals (Sweden)

Anne K. Braczynski

2015-01-01

Full Text Available TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment.

Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2

Science.gov (United States)

Fedier, A; Ruefenacht, U B; Schwarz, V A; Haller, U; Fink, D

2002-01-01

A large fraction of human tumours carries mutations in the p53 gene. p53 plays a central role in controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack of p53 function impairs these cellular processes, and this may be the basis of resistance to chemotherapeutic regimens. By virtue of the involvement of DNA mismatch repair in modulating cytotoxic pathways in response to DNA damaging agents, we investigated the effects of loss of Pms2 on the sensitivity to a panel of widely used anticancer agents in E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient in Pms2. We report that lack of the Pms2 gene is associated with an increased sensitivity, ranging from 2–6-fold, to some types of anticancer agents including the topoisomerase II poisons doxorubicin, etoposide and mitoxantrone, the platinum compounds cisplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, and the antimetabolite gemcitabine. In contrast, no change in sensitivity was found after treatment with 5-fluorouracil. Cell cycle analysis revealed that both, Pms2-deficient and -proficient cells, retain the ability to arrest at the G2/M upon cisplatin treatment. The data indicate that the concomitant loss of Pms2 function chemosensitises p53-deficient cells to some types of anticancer agents, that Pms2 positively modulates cell survival by mechanisms independent of p53, and that increased cytotoxicity is paralleled by increased apoptosis. Tumour-targeted functional inhibition of Pms2 may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers. British Journal of Cancer (2002) 87, 1027–1033. doi:10.1038/sj.bjc.6600599 www.bjcancer.com © 2002 Cancer Research UK PMID:12434296

Synergistic effect of factor VII gene polymorphisms causing mild factor VII deficiency in a case of severe factor X deficiency.

Science.gov (United States)

Deshpande, Rutuja; Ghosh, Kanjaksha; Shetty, Shrimati

2017-01-01

Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation.

Resurrection of vitamin D deficiency and rickets

Science.gov (United States)

Holick, Michael F.

2006-01-01

The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children. PMID:16886050

Cobalamin Deficiency: Clinical Picture and Radiological Findings

Directory of Open Access Journals (Sweden)

Chiara Briani

2013-11-01

Full Text Available Vitamin B12 deficiency causes a wide range of hematological, gastrointestinal, psychiatric and neurological disorders. Hematological presentation of cobalamin deficiency ranges from the incidental increase of mean corpuscular volume and neutrophil hypersegmentation to symptoms due to severe anemia, such as angor, dyspnea on exertion, fatigue or symptoms related to congestive heart failure, such as ankle edema, orthopnea and nocturia. Neuropsychiatric symptoms may precede hematologic signs and are represented by myelopathy, neuropathy, dementia and, less often, optic nerve atrophy. The spinal cord manifestation, subacute combined degeneration (SCD, is characterized by symmetric dysesthesia, disturbance of position sense and spastic paraparesis or tetraparesis. The most consistent MRI finding is a symmetrical abnormally increased T2 signal intensity confined to posterior or posterior and lateral columns in the cervical and thoracic spinal cord. Isolated peripheral neuropathy is less frequent, but likely overlooked. Vitamin B12 deficiency has been correlated negatively with cognitive functioning in healthy elderly subjects. Symptoms include slow mentation, memory impairment, attention deficits and dementia. Optic neuropathy occurs occasionally in adult patient. It is characterized by symmetric, painless and progressive visual loss. Parenteral replacement therapy should be started soon after the vitamin deficiency has been established.

Triacylglycerol infusion does not improve hyperlactemia in resting patients with mitochondrial myopathy due to complex I deficiency

NARCIS (Netherlands)

Roef, MJ; de Meer, K; Reijngoud, DJ; Straver, HWHC; de Barse, M; Kalhan, SC; Berger, R

Background: A high-fat diet has been recommended for correction of biochemical abnormalities and muscle energy state in patients with complex I (NADH dehydrogenase) deficiency (CID). Objective: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or

Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

Directory of Open Access Journals (Sweden)

Nadia Charfi

2012-01-01

Full Text Available Congenital adrenal hyperplasia (CAH describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs. Leydig cell tumors (LCTs are make up a very small number of all testicular tumors and can be difficult to distinguish from TARTs. This distinction is interesting because LCTs and TARTs require different therapeutic approaches. Hereby, we present an unusual case of a 19-year-old patient with CAH due to 11β-hydroxylase deficiency, who presented with TARTs and an epididymal Leydig cell tumor.

Inside-out neuropharmacology of nicotinic drugs.

Science.gov (United States)

Henderson, Brandon J; Lester, Henry A

2015-09-01

Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as "inside-out pharmacology". This term contrasts with the better-known, acute, "outside-in" effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complement factor H deficiency and endocapillary glomerulonephritis due to paternal isodisomy and a novel factor H mutation

DEFF Research Database (Denmark)

Schejbel, L; Schmidt, I M; Kirchhoff, Eva Maria

2011-01-01

Complement factor H (CFH) is a regulator of the alternative complement activation pathway. Mutations in the CFH gene are associated with atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II and C3 glomerulonephritis. Here, we report a 6-month-old CFH-deficient child...

Seven Patients With Transcobalamin Deficiency Diagnosed Between 2010 and 2014

DEFF Research Database (Denmark)

Yildirim, Zuhal K; Nexo, Ebba; Rupar, Tony

2017-01-01

Transcobalamin deficiency (OMIM 275350) is a rare autosomal recessive disease presenting with nonspecific clinical features in early infancy. We report the clinical and laboratory manifestations of 7 children diagnosed with transcobalamin deficiency. All patients were admitted between 2 and 4 mon....... In conclusion, 1 mg of intramuscular CN-Cbl every week suffices for hematological improvement but not for normal neurological development in patients who all had relapse due to decrease or cessation of treatment....

Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?

Science.gov (United States)

Laron, Zvi

2005-02-01

Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.

Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency

NARCIS (Netherlands)

Logt, A.E. van de; Kluijtmans, L.A.J.; Huigen, M.C.; Janssen, M.C.H.

2017-01-01

A 59-year-old woman, with a medical history of intellectual disability after perinatal asphyxia, was admitted because of coma due to hyperammonemia after she was treated for a fracture of the pelvis. The ammonia level was 280 muM. Acquired disorders as explanation for the hyperammonemia were

Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

Energy Technology Data Exchange (ETDEWEB)

Gu, Y.

1989-01-01

The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the {alpha}-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced {sup 22}Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the {gamma}, {delta}, and {epsilon} subunit, respectively, of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four ({alpha}, {beta}, {gamma}, and {delta}) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the {alpha}, {beta}, and {delta} subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the {gamma}- and {epsilon}- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the {gamma} is replaced by {epsilon}.

Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

International Nuclear Information System (INIS)

Gu, Y.

1989-01-01

The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the α-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced 22 Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the γ, δ, and ε subunit, respectively, of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four (α, β, γ, and δ) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the α, β, and δ subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the γ- and ε- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the γ is replaced by ε

Central Nervous System Symptoms Due to Transient Methemoglobinemia in a Child With G6PD Deficiency.

Science.gov (United States)

Sharma, Shreya; Srinivasaraghavan, Rangan; Krishnamurthy, Sriram

2017-01-01

The authors herein report a 5-year-old child who presented with massive hemolysis, irritability, and cyanosis. The final diagnosis was glucose-6-phosphate dehydrogenase deficiency with associated central nervous system symptoms probably because of concomitantly acquired methemoglobinemia following oxidant drug exposure. The associated acute-onset anemia would have contributed to the development of cerebral anoxia-related seizures and encephalopathy.

How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID).

Science.gov (United States)

Kohn, Donald B; Gaspar, H Bobby

2017-05-01

Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

Respiratory chain complex I deficiency due to NDUFA12 mutations as a new cause of Leigh syndrome

DEFF Research Database (Denmark)

Ostergaard, Elsebet; Rodenburg, Richard J; van den Brand, Mariël

2011-01-01

This study investigated a girl with Leigh syndrome born to first-cousin parents of Pakistani descent with an isolated respiratory chain complex I deficiency in muscle and fibroblasts. Her early development was delayed, and from age 2 years she started losing motor abilities. Cerebral MRI showed...

Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease

NARCIS (Netherlands)

Rabelink, N.M.; Westgeest, H.M.; Bravenboer, N.; Jacobs, M.A.J.M.; Lips, P.T.A.M.

2011-01-01

Case report A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which

Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation/carnitine transporter OCTN2

NARCIS (Netherlands)

Spiekerkoetter, U.; Huener, G.; Baykal, T.; Demirkol, M.; Duran, M.; Wanders, R.; Nezu, J.; Mayatepek, E.

2003-01-01

A family of Turkish origin with primary systemic carnitine deficiency in the father and his two sons is described. In all three individuals, the same homozygous mutation in the OCTN2 gene (R471H) was present and carnitine uptake in fibroblasts was deficient. Whereas one boy became symptomatic with a

Growth hormone deficiency and pituitary malformation in a recurrent Cat-Eye syndrome: a family report.

Science.gov (United States)

Jedraszak, Guillaume; Braun, Karine; Receveur, Aline; Decamp, Matthieu; Andrieux, Joris; Rabbind Singh, Amrathlal; Copin, Henri; Bremond-Gignac, Dominique; Mathieu, Michèle; Rochette, Jacques; Morin, Gilles

2015-10-01

Growth hormone deficiency affects roughly between one in 3000 and one in 4000 children with most instances of growth hormone deficiency being idiopathic. Growth hormone deficiency can also be associated with genetic diseases or chromosome abnormalities. Association of growth hormone deficiency together with hypothalamic-pituitary axis malformation and Cat-Eye syndrome is a very rare condition. We report a family with two brothers presenting with growth delay due to a growth hormone deficiency associated with a polymalformation syndrome. They both displayed pre-auricular pits and tags, imperforate anus and Duane retraction syndrome. Both parents and a third unaffected son displayed normal growth pattern. Cerebral MRI showed a hypothalamic-pituitary axis malformation in the two affected brothers. Cytogenetic studies revealed a type I small supernumerary marker chromosome derived from chromosome 22 resulting in a tetrasomy 22pter-22q11.21 characteristic of the Cat-Eye syndrome. The small supernumerary marker chromosome was present in the two affected sons and the mother in a mosaic state. Patients with short stature due to growth hormone deficiency should be evaluated for chromosomal abnormality. Family study should not be underestimated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Progranulin Overproduction Due to Fli-1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis.

Science.gov (United States)

Ichimura, Yohei; Asano, Yoshihide; Akamata, Kaname; Noda, Shinji; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

2015-12-01

Progranulin is a growth factor that is active in wound repair and is an antagonist of tumor necrosis factor (TNF) receptors, regulating fibroblast activation, angiogenesis, and inflammation. Because long-standing activation of gene programs related to wound healing is a hallmark of systemic sclerosis (SSc), we sought to investigate the role of progranulin in SSc. Progranulin expression levels in human and murine skin samples were determined by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. The role of progranulin in fibroblast activation was examined using a gene-silencing technique. Progranulin levels in serum obtained from 60 patients with SSc and 16 healthy control subjects were determined by enzyme-linked immunosorbent assay. Progranulin expression was increased in SSc dermal fibroblasts compared with normal dermal fibroblasts, both in vivo and in vitro. Transcription factor Fli-1, a deficiency of which is involved in the activation of SSc dermal fibroblasts, served as a potent repressor of the progranulin gene, and Fli-1(+/-) mice and bleomycin-treated wild-type mice exhibited up-regulated expression of progranulin in dermal fibroblasts. SSc dermal fibroblasts were resistant to the antifibrotic effect of TNF, but this resistance was reversed by gene silencing of progranulin. Serum progranulin levels were elevated in patients with early diffuse cutaneous SSc (dcSSc), especially in those with inflammatory skin symptoms, and were positively correlated with the C-reactive protein level. Progranulin overproduction due to Fli-1 deficiency may contribute to the constitutive activation of SSc dermal fibroblasts by antagonizing the antifibrotic effect of TNF. Progranulin may also be involved in the inflammatory process associated with progressive skin sclerosis in early dcSSc. © 2015, American College of Rheumatology.

Vitamin Deficiency Anemia

Science.gov (United States)

... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

Deficiência de ferro no feto e no recém-nascido Iron deficiency in the fetus and newborn

Directory of Open Access Journals (Sweden)

Maria Renata T. Chopard

2010-06-01

Full Text Available A principal causa de anemia no feto é a doença hemolítica do recém-nascido (RN. As gestantes anêmicas na sua forma moderada não acarretam baixos estoques de ferro no concepto, porém podem evoluir para o trabalho de parto prematuro e RN com baixo peso ao nascer. O ferro é transportado para o feto por via transplacentária, principalmente durante o terceiro trimestre de gestação. A deficiência de ferro não ocorre no período neonatal, porém os prematuros e ou RN com baixo peso constituem o principal grupo de risco para desenvolver a deficiência de ferro. Nos RN nascidos a termo podemos observar uma deficiência de ferro naqueles que sofreram ressecção cirúrgica do duodeno devido à malformação congênita. A fim de evitarmos a deficiência de ferro neste grupo de risco, indica-se a suplementação de ferro a partir dos 30 dias de vida. A via de administração preferencial é a enteral, apesar de sabermos que no prematuro ocorre uma deficiência do controle da absorção do ferro. O complexo de ferro polimaltosado e o ferro aminoquelado são os de escolha para a profilaxia da deficiência de ferro em prematuros. A via endovenosa é segura e não acarreta piora das lesões causadas pela ação oxidativa do ferro em prematuros.The main cause of anemia in the fetus is hemolytic disease. Mildly anemic pregnant women may evolve with premature labor and have low birth weight babies, but the baby's iron status is not influenced by the mother's iron deficiency. Iron transportation through the placenta occurs in the third trimester of gestation and premature labor results in reduced iron stores. Iron deficiency anemia does not occur during the neonatal period, but premature and low birth weight babies are at risk of developing iron deficiency. In full-term babies iron deficiency can occur due to intestinal malformation that leads to duodenal resection. To avoid iron deficiency in at-risk babies, iron supplementation is recommended from

Resistance to rocuronium of rat diaphragm as compared with limb muscles.

Science.gov (United States)

Huang, Lina; Yang, Meirong; Chen, Lianhua; Li, Shitong

2014-12-01

Skeletal muscles are composed of different muscle fiber types. We investigated the different potency to rocuronium among diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL) in vitro as well as to investigate the differences of acetylcholine receptors (AChRs) among these three typical kinds of muscles. The isolated left hemidiaphragm nerve-muscle preparations, the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations were established to evaluate the potency to rocuronium. Concentration-response curves were constructed and the values of IC50 were obtained. The density of AChRs at the end plate and the number of AChRs per unit fiber cross fiber area (CSA), AChR affinity for muscle relaxants were evaluated. The concentration-twitch tension curves of rocuronium were significantly different. The curves demonstrated a shift to the right of the DIA compared with the EDL and SOL (P  0.05). IC50 was significantly largest in DIA, second largest in SOL, and smallest in EDL (P rocuronium of DIA compared with EDL and SOL was verified. The DIA was characterized by the largest number of AChRs per unit fiber CSA and the lowest affinity of the AChRs. Although compared with SOL, EDL was proved to have larger number of AChRs per unit fiber CSA and the lower affinity of the AChRs. These findings may be the mechanisms of different potency to rocuronium in DIA, EDL, and SOL. The results of the study could help to explain the relationship between different composition of muscle fibers and the potency to muscle relaxants. Extra caution should be taken in clinical practice when monitoring muscle relaxation in anesthetic management using different muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

Encoding of QC-LDPC Codes of Rank Deficient Parity Matrix

Directory of Open Access Journals (Sweden)

Mohammed Kasim Mohammed Al-Haddad

2016-05-01

Full Text Available the encoding of long low density parity check (LDPC codes presents a challenge compared to its decoding. The Quasi Cyclic (QC LDPC codes offer the advantage for reducing the complexity for both encoding and decoding due to its QC structure. Most QC-LDPC codes have rank deficient parity matrix and this introduces extra complexity over the codes with full rank parity matrix. In this paper an encoding scheme of QC-LDPC codes is presented that is suitable for codes with full rank parity matrix and rank deficient parity matrx. The extra effort required by the codes with rank deficient parity matrix over the codes of full rank parity matrix is investigated.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

Subacute copper-deficiency myelopathy in a patient with occult celiac disease.

Science.gov (United States)

Cavallieri, Francesco; Fini, Nicola; Contardi, Sara; Fiorini, Massimo; Corradini, Elena; Valzania, Franco

2017-07-01

Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms.

What Are Rare Clotting Factor Deficiencies?

Science.gov (United States)

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management.

Science.gov (United States)

Cappellini, Maria Domenica; Comin-Colet, Josep; de Francisco, Angel; Dignass, Axel; Doehner, Wolfram; Lam, Carolyn S; Macdougall, Iain C; Rogler, Gerhard; Camaschella, Clara; Kadir, Rezan; Kassebaum, Nicholas J; Spahn, Donat R; Taher, Ali T; Musallam, Khaled M

2017-10-01

Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease-specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

Causas genéticas de deficiência de ferro Genetic causes for iron deficiency

Directory of Open Access Journals (Sweden)

Sara Teresinha O. Saad

2010-06-01

Full Text Available As causas genéticas de deficiência de ferro, real ou funcional, ocorrem por defeitos em muitas proteínas envolvidas na absorção e metabolismo de ferro. Neste capítulo descreveremos sucintamente causas genéticas de carência de ferro para a síntese de hemoglobina, que cursa então com anemia microcítica e hipocrômica. Ressalto que estas são alterações raras, com poucas descrições na literatura. Em alguns casos, o ferro funcional não está disponível para os eritroblastos sintetizarem hemoglobina, ou o eritroblasto é incapaz de captar ferro da circulação, mas o ferro está acumulado em tecidos ou nas mitocôndrias. Nos últimos anos, várias descobertas, principalmente oriundas de descrições em humanos ou de modelos animais, ajudaram a elucidar a implicação dos componentes do metabolismo do ferro na deficiência de ferro hereditária, que afetam desde a absorção intestinal até sua inclusão final no heme.The genetic causes of iron deficiency, real or functional, occur due to defects in many proteins involved in the absorption and metabolism of iron. In this chapter we briefly describe the genetic causes of iron deficiency in the synthesis of hemoglobin, resulting in hypochromic or microcytic anemia. These alterations are rare with few descriptions in the literature. In some cases, functional iron is not available for erythroblasts to synthesis hemoglobin, or erythroblasts may be incapable of capturing iron from the circulation although iron is accumulated in tissues and mitochondrias. Many discoveries have been made over the last few years, mainly resulting from the description of human or animal models, which have elucidated the implications of the components in iron metabolism in hereditary iron deficiency involving all processes from intestinal absorption to the final inclusion into heme.

Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice.

Directory of Open Access Journals (Sweden)

Martine Bot

Full Text Available AIMS: Altered sphingosine 1-phosphate (S1P homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/- deficiency on leukocyte subsets relevant to atherosclerosis. METHODS AND RESULTS: LDL receptor deficient mice that were transplanted with Sgpl1(-/- bone marrow showed disrupted S1P gradients translating into lymphopenia and abrogated lymphocyte mitogenic and cytokine response as compared to controls. Remarkably however, Sgpl1(-/- chimeras displayed mild monocytosis, due to impeded stromal retention and myelopoiesis, and plasma cytokine and macrophage expression patterns, that were largely compatible with classical macrophage activation. Collectively these two phenotypic features of Sgpl1 deficiency culminated in diminished atherogenic response. CONCLUSIONS: Here we not only firmly establish the critical role of hematopoietic S1P lyase in controlling S1P levels and T cell trafficking in blood and lymphoid tissue, but also identify leukocyte Sgpl1 as critical factor in monocyte macrophage differentiation and function. Its, partly counterbalancing, pro- and anti-inflammatory activity spectrum imply that intervention in S1P lyase function in inflammatory disorders such as atherosclerosis should be considered with caution.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

“Myasthenia Gravis and Anesthesia – A Review of the Literature ...

African Journals Online (AJOL)

Myasthenia gravis (MG) is an immunological disorder characterized by damaged acetylcholine receptors (AchR) due to antibody, which not only blocks the receptor site but also causes degenerations of the receptors.. It is closely associated with disorders of similar pathogenesis, such as pernicious anaemia, thyrotoxicosis, ...

Effect of pyridoxine deficiency on cholesterogenesis in rats fed different levels of protein

International Nuclear Information System (INIS)

Okada, Mitsuko; Iwami, Tamako

1977-01-01

Hepatic cholesterol contents in rats fed a 70% or 20% casein diet with or without pyridoxine was determined. In the case of the 70% casein group, pyridoxine-deficient rats showed a higher content than the control. The increment was mainly due to the accumulation of an ester form of the cholesterol. On the other hand, pyridoxine-deficient rats in the 20% casein group showed a slightly lower content. The cholesterol content in liver microsomal fractions was lower in the 20%-casein pyridoxine-deficient group and serum cholesterol level was lower in the 70%-casein pyridoxine-deficient group than those in respective control groups. Incorporation of [ 14 C] acetate into cholesterol was studied using liver slices, and significant stimulation was observed in pyridoxine-deficient rat fed a 20% or 70% casein diet. There was no difference in intestinal cholesterogenesis between the control and the deficient groups. (auth.)

Metabolic profile and cardiovascular risk factors in adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Directory of Open Access Journals (Sweden)

Mouna Feki Mnif

2012-01-01

Full Text Available Background: In congenital adrenal hyperplasia (CAH, long-term glucocorticoid treatment coupled with increased androgens may lead to undesirable metabolic effects. The aim of our report was to determine the prevalence of metabolic abnormalities and cardiovascular risk factors in a population of adult patients with CAH due to 21 hydroxylase deficiency. Materials and Methods: Twenty-six patients (11 males and 15 females, mean age ± SD=27.4±8.2 years were recruited. Anthropometry, body composition, metabolic parameters and cardiovascular risk factors were studied. Results: Obesity (overweight included was noted in 16 patients (61.5%, with android distribution in all cases. Bioelectrical impedance showed increased body fat mass in 12 patients (46.1%. Lipid profile alterations and carbohydrate metabolism disorders were detected in seven (26.9% and five (19.2% patients respectively. Moderate hepatic cytolysis, associated with hepatic steatosis, was found in one patient. Seven patients (27% had insulin resistance. Ambulatory blood pressure monitoring showed abnormalities in six patients (23%. Increased carotid intima media thickness was found in 14 patients (53.8%. Conclusion: Adult CAH patients tend to have altered metabolic parameters and a higher prevalence of cardiovascular risk factors. Lifelong follow-up, lifestyle modifications, and attempts to adjust and reduce the glucocorticoid doses seem important.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... anemia, your doctor may order the following blood tests to diagnose iron-deficiency anemia: Complete blood count (CBC) to ... than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency anemia. In iron-deficiency anemia, blood ...

Successful medical management of acute mesenteric ischemia due to superior mesenteric and portal vein thrombosis in a 27-year-old man with protein S deficiency: a case report.

Science.gov (United States)

Osti, N P; Sah, D N; Bhandari, R S

2017-11-09

Acute mesenteric ischemia poses a diagnostic challenge due to nonspecific clinical clues and lack of awareness owing to its rarity. Ischemia due to mesenteric venous thrombosis has a good prognosis compared to arterial cause and can be managed conservatively with early diagnosis. The portomesenteric venous system is an unusual site of thrombosis in patients with protein S deficiency, and its thrombosis is an uncommon cause of acute mesenteric ischemia. We present a case of a 27-year-old Mongolian man who presented with acute abdominal pain increasing in severity, and refractory to repeated attempts at treatment with a misdiagnosis of acute peptic ulcer disease. Contrast-enhanced computed tomography of his abdomen detected complete occlusion of the superior mesenteric vein, an extension of acute thrombus into the portal vein, and ischemic mid-jejunal loops. Early diagnosis and immediate anticoagulation with continuous intravenous infusion of unfractionated heparin prevented subsequent consequences. On further workup, our patient was diagnosed with isolated protein S deficiency. We started lifelong thromboprophylaxis with warfarin to prevent recurrence and our patient was asymptomatic on the latest follow-up 5 months after discharge. Despite accurate detection of acute mesenteric ischemia by contrast-enhanced computed tomography, high index of suspicion is indispensable for its early diagnosis. Early diagnosis and immediate anticoagulation will prevent subsequent complications and need for surgical intervention. Young patients without known risk factors presenting with venous thrombosis in atypical sites should be investigated for prothrombotic diseases.

Health Deficiencies

Data.gov (United States)

U.S. Department of Health & Human Services — A list of all health deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

Simple Method To Distinguish between Primary and Secondary C3 Deficiencies

OpenAIRE

Pereira de Carvalho Florido, Marlene; Ferreira de Paula, Patrícia; Isaac, Lourdes

2003-01-01

Due to the increasing numbers of reported clinical cases of complement deficiency in medical centers, clinicians are now more aware of the role of the complement system in the protection against infections caused by microorganisms. Therefore, clinical laboratories are now prepared to perform a number of diagnostic tests of the complement system other than the standard 50% hemolytic component assay. Deficiencies of alternative complement pathway proteins are related to severe and recurrent inf...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... if you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron-deficiency anemia because of your age, ... or sex. Age You may be at increased risk for iron deficiency at certain ages: Infants between ...

Leaf and canopy photosynthesis of a chlorophyll deficient soybean mutant.

Science.gov (United States)

Sakowska, Karolina; Alberti, Giorgio; Genesio, Lorenzo; Peressotti, Alessandro; Delle Vedove, Gemini; Gianelle, Damiano; Colombo, Roberto; Rodeghiero, Mirco; Panigada, Cinzia; Juszczak, Radosław; Celesti, Marco; Rossini, Micol; Haworth, Matthew; Campbell, Benjamin W; Mevy, Jean-Philippe; Vescovo, Loris; Cendrero-Mateo, M Pilar; Rascher, Uwe; Miglietta, Franco

2018-03-02

The photosynthetic, optical, and morphological characteristics of a chlorophyll-deficient (Chl-deficient) "yellow" soybean mutant (MinnGold) were examined in comparison with 2 green varieties (MN0095 and Eiko). Despite the large difference in Chl content, similar leaf photosynthesis rates were maintained in the Chl-deficient mutant by offsetting the reduced absorption of red photons by a small increase in photochemical efficiency and lower non-photochemical quenching. When grown in the field, at full canopy cover, the mutants reflected a significantly larger proportion of incoming shortwave radiation, but the total canopy light absorption was only slightly reduced, most likely due to a deeper penetration of light into the canopy space. As a consequence, canopy-scale gross primary production and ecosystem respiration were comparable between the Chl-deficient mutant and the green variety. However, total biomass production was lower in the mutant, which indicates that processes other than steady state photosynthesis caused a reduction in biomass accumulation over time. Analysis of non-photochemical quenching relaxation and gas exchange in Chl-deficient and green leaves after transitions from high to low light conditions suggested that dynamic photosynthesis might be responsible for the reduced biomass production in the Chl-deficient mutant under field conditions. © 2018 John Wiley & Sons Ltd.

Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency.

Science.gov (United States)

Richter, Susan; Peitzsch, Mirko; Rapizzi, Elena; Lenders, Jacques W; Qin, Nan; de Cubas, Aguirre A; Schiavi, Francesca; Rao, Jyotsna U; Beuschlein, Felix; Quinkler, Marcus; Timmers, Henri J; Opocher, Giuseppe; Mannelli, Massimo; Pacak, Karel; Robledo, Mercedes; Eisenhofer, Graeme

2014-10-01

Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. We assessed whether altered succinate dehydrogenase product-precursor relationships, manifested by differences in tumor ratios of succinate to fumarate or other metabolites, might aid in identifying and stratifying patients with SDHx mutations. PPGL tumor specimens from 233 patients, including 45 with SDHx mutations, were provided from eight tertiary referral centers for mass spectrometric analyses of Krebs cycle metabolites. Diagnostic performance of the succinate:fumarate ratio for identification of pathogenic SDHx mutations. SDH-deficient PPGLs were characterized by 25-fold higher succinate and 80% lower fumarate, cis-aconitate, and isocitrate tissue levels than PPGLs without SDHx mutations. Receiver-operating characteristic curves for use of ratios of succinate to fumarate or to cis-aconitate and isocitrate to identify SDHx mutations indicated areas under curves of 0.94 to 0.96; an optimal cut-off of 97.7 for the succinate:fumarate ratio provided a diagnostic sensitivity of 93% at a specificity of 97% to identify SDHX-mutated PPGLs. Succinate:fumarate ratios were higher in both SDHB-mutated and metastatic tumors than in those due to SDHD/C mutations or without metastases. Mass spectrometric-based measurements of ratios of succinate:fumarate and other metabolites in PPGLs offer a useful method to identify patients for testing of SDHx mutations, with additional utility to quantitatively assess functionality of mutations and metabolic factors responsible for malignant risk.

Situation of Iron Deficiency and Its Management Prioritizing Dietary Intervention in Nepal

DEFF Research Database (Denmark)

Adhikari, BK; Koirala, U; Lama, STA

2012-01-01

the extent of iron deficiency anemia and intake of dietary iron among the general population in Nepal. Materials and methods Published research articles, books, bulletins, and online materials regarding iron deficiency were studied in both national and international scenarios. Results Nearly 46 percent...... of children (6–59 months) and 35 percent of women (15–49 years) were still suffering from anemia though the trend has been decreasing for the last 15 years. Mostly, young children (6–23 months) and pregnant women were the victims due to their high iron requirements and lower intake of dietary iron. The most...... common risk factors related to iron deficiency anemia (IDA) found in different studies were low intake of dietary iron, vitamin A deficiency, hookworm infection, malaria, heavy menstrual blood loss, and multiparity. Iron deficiency situation in the Nepalese population is triggered by Illiteracy, lack...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Topics News & Resources Intramural Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer ... and symptoms as well as complications from iron-deficiency anemia. Research for Your Health The NHLBI is part of the U.S. Department ...

Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

Science.gov (United States)

Reish, O; Townsend, D; Berry, S A; Tsai, M Y; King, R A

1995-01-01

Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase. Images Figure 1 PMID:7611281

A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis

Directory of Open Access Journals (Sweden)

Ram Nanik

2012-12-01

Full Text Available Abstract Background Familial glucocorticoid deficiency (FGD is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency in the presence of normal plasma renin and aldosterone level. Focal segmental glomerulosclerosis (FSGS is a form of glomerular disease associated with proteinuria and nephritic syndrome. This is the first case of familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. Case presentation An eight month old boy presented with increased genital pigmentation. Initial investigation revealed that he was glucocorticoid deficient and was started on hydrocortisone and fludrocortisone with a diagnosis of primary adrenal insufficiency. Later fludrocortisone was withdrawn and he was diagnosed to have isolated glucocorticoid deficiency. He later developed focal segmental glomerulosclerosis for which he underwent renal transplantation at the age of five years. Now at the age of twelve years, this boy is doing well on hydrocortisone treatment. His two siblings and a first degree cousin also had isolated glucocorticoid deficiency. One of the above two siblings died due to renal failure secondary to focal segmental glomerulosclerosis. Conclusion Patients with familial glucocorticoid deficiency should be carefully followed for development of features of nephrotic syndrome.

IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging.

Science.gov (United States)

Toth, Peter; Tarantini, Stefano; Ashpole, Nicole M; Tucsek, Zsuzsanna; Milne, Ginger L; Valcarcel-Ares, Noa M; Menyhart, Akos; Farkas, Eszter; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2015-12-01

Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1(f/f) -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Molecular basis for genetic deficiency of the second component of human complement

International Nuclear Information System (INIS)

Cole, F.S.; Whitehead, A.S.; Auerbach, H.S.; Lint, T.; Zeitz, H.J.; Kilbridge, P.; Colten, H.R.

1985-01-01

Genetic deficiency of the second component of complement (C2) is the most common complement-deficiency state among Western Europeans and is frequently associated with autoimmune diseases. To examine the molecular basis of this deficiency, the authors established cultures of blood monocytes from four families with C2-deficient members. Using a hemolytic-plaque assay, [ 35 S]methionine metabolic labeling of proteins in tissue culture and immunoprecipitation, RNA extraction and Northern blot analysis, and DNA restriction-enzyme digestion and Southern blot analysis, the authors found that C2 deficiency is not due to a major gene deletion or rearrangement but is the result of a specific and selective pretranslational regulatory defect in C2 gene expression. This leads to a lack of detectable C2 mRNA and a lack of synthesis of C2 protein. The approach used in this study should prove useful in examination of other plasma protein deficiencies, especially those in which the deficient gene is normally expressed in peripheral-blood monocytes or tissue macrophages and in which ethical considerations preclude the use of liver or other tissue for study

Reconstructive surgery for females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a review from the Prince of Wales Hospital.

Science.gov (United States)

Houben, C H; Tsui, S Y; Mou, J W; Chan, K W; Tam, Y H; Lee, K H

2014-12-01

To present the results of feminising genitoplasty done in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Case series. A tertiary referral centre in Hong Kong. Female patients with congenital adrenal hyperplasia undergoing corrective surgery for virilisation between 1993 and 2012. The operative result was judged with a scoring system (1-3) for four areas: appearance of clitoris, labia and vagina, plus requirement for revision surgery. A total of 23 female patients with congenital adrenal hyperplasia with a median age of 17.5 (range, 1.5-33.8) years were identified. Of these individuals, 17 presented in the neonatal period and early infancy, of which four had an additional salt-losing crisis. Six patients-including four migrants from mainland China-were late presenters at a median age of 2 (range, 0.5-14) years. Twenty-two patients had corrective surgery at a median age of 2 (range, 1-14) years. Clitoral reduction was performed in all, and further surgery in 21 patients. The additional surgery was flap vaginoplasty in 10 patients, a modified Passerini procedure in six, and a labial reconstruction in five; one patient with prominent clitoris was for observation only. Minor revision surgery (eg mucosal trimming) was required in three patients; a revision vaginoplasty was done in one individual. Of the 23 patients, 18 (78%) with a median age of 20 (range, 9.3-33.8) years participated in the outcome evaluation: a 'good' outcome (4 points) was seen in 12 patients and a 'satisfactory' (5-9 points) result in five patients. Nearly three quarters of our cohort (n=17) presented with classic virilising form of 21-hydroxylase deficiency. Only four (25%) patients experienced a salt-losing crisis. Female gender assignment at birth was maintained for all individuals in this group. 'Good' and 'satisfactory' outcomes of surgery were reported in nearly all participants.

Effects of Nutrient Deficiencies in Corn Plants on the In Vivo and In Vitro Metabolism of [14C] Diazinon

International Nuclear Information System (INIS)

Kunstman, J.L.; Lichtenstein, E.P.

1981-01-01

Full text: The effects of calcium, nitrogen, and magnesium deficiencies on the penetration, translocation, and the in vivo and in vitro metabolism of the insecticide [ 14 C] diazinon (diethyl-2-isopropyl-6-methyl-4-pyrimidinyl) in corn plants were investigated. On a per gram fresh weight basis only roots from nitrogen-deficient solutions contained less C while tops from plants grown in calcium-deficient solutions contained nearly four times more radiocarbon than those from complete nutrient solutions. Due to calcium or nitrogen deficiencies a reduced degradation occurred in roots as indicated by the relatively higher recoveries of diazinon and the lower recoveries of an unidentified, more polar 14 C-ring compound. No differencies in [ 14 C] diazinon degradation due to nutrient deficiencies were noticeable with corn tops. The metabolic activity of corn roots was due to a soluble enzyme. In studies with subcellular components from roots, specific activities increased from the homogenate (4.09%/mg of protein) to the 105000 g supernatant (7.77%/mg of protein). Subcellular components from calcium-deficient roots produced significantly less water-soluble radiocarbon (sp act., 0.60) than did control roots (sp act., 1.60), results similar to those observed with in vivo experiments. However, the 10000 g supernatant from root material deficient in nitrogen produced significantly more water—soluble radiocarbon (sp act., 2.85) than subcellular fractions from control roots. (author)

Cobalamin deficiency associated with erythroblastic anemia and methylmalonic aciduria in a border collie.

Science.gov (United States)

Morgan, L W; McConnell, J

1999-01-01

Anemia due to cobalamin deficiency is a rare genetic disorder that has been recognized in dogs only recently. This report concerns a 14-month-old border collie that presented for chronic, nonregenerative anemia. Cytological examination of a peripheral blood smear showed the presence of erythroblasts. Serum cobalamin levels were below reference ranges reported for clinically normal dogs. A methylmalonic aciduria was found on urinalysis. These signs are consistent with the anemia in Imerslund-Graesbeck syndrome reported in humans. Anemia due to cobalamin deficiency responds to parenteral vitamin B12 therapy, and affected animals have a good prognosis for recovery.

Iodine deficiency disorders

Energy Technology Data Exchange (ETDEWEB)

Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

1994-12-31

Iodine deficiency (IDD) is one of the common problem in the diet. Iodine deficiency as prevalence of goiter in population occurs in the mountainous areas. There is consensus that 800 million people are at risk of IDD from living in iodine deficient area and 190 million from goiter. Very high prevalence of IDD in different parts of the world are striking. It has generally observed that in iodine-deficient areas about 50% are affected with goiter, 1-5% from cretinsim and 20% from impaired mental and/or mortor function. (A.B.).

Skin wound healing in MMP2-deficient and MMP2 / plasminogen double-deficient mice

DEFF Research Database (Denmark)

Frøssing, Signe; Rønø, Birgitte; Hald, Andreas

2010-01-01

-sensitive MMPs during wound healing. To address whether MMP2 is accountable for the galardin-induced healing deficiency in wildtype and Plg-deficient mice, incisional skin wounds were generated in MMP2 single-deficient mice and in MMP2/Plg double-deficient mice and followed until healed. Alternatively, tissue...... was isolated 7 days post wounding for histological and biochemical analyses. No difference was found in the time from wounding to overt gross restoration of the epidermal surface between MMP2-deficient and wildtype control littermate mice. MMP2/Plg double-deficient mice were viable and fertile, and displayed...... an unchallenged general phenotype resembling that of Plg-deficient mice, including development of rectal prolapses. MMP2/Plg double-deficient mice displayed a slight increase in the wound length throughout the healing period compared with Plg-deficient mice. However, the overall time to complete healing...

Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

NARCIS (Netherlands)

Oosterveer, Maaike H.; Koolman, Anniek H.; de Boer, Pieter T.; Bos, Trijnie; Bleeker, Aycha; Bloks, Vincent W.; Kuipers, Folkert; Sauer, Pieter J. J.; van Dijk, Gertjan

2011-01-01

Background: Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat

Delayed diagnosis of congenital adrenal hyperplasia with salt wasting due to type II 3beta-hydroxysteroid dehydrogenase deficiency

DEFF Research Database (Denmark)

Johannsen, Trine H; Mallet, Delphine; Dige-Petersen, Harriet

2005-01-01

Classical 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3beta-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slig...

Deficiência de ferro na criança Iron deficiency in infants and children

Directory of Open Access Journals (Sweden)

Josefina A. P. Braga

2010-06-01

diet and early weaning contribute to the high prevalence, mainly within the first 2 years of life. Other risk factors, such as prematurity, low birth weight, early umbilical cord clamping and weaning from exclusive breastfeeding may contribute. The impact of iron deficiency on growth is controversial as several other variables contribute to improve or worsen the nutritional status. Alterations in the psychomotor and neural-cognitive development of infants with iron deficiency have been reported in various studies with the catch-up growth rate after treatment being controversial. Additionally, some studies have demonstrated a decrease in the intellectual development and cognitive acquisition in school age children and adolescents that is reverted after iron therapy. The best preventive measure is nutritional education, however due to the high prevalence of iron deficiency anemia, other measures should also be used as iron supplementation and food fortification with iron.

Beriberi (thiamine deficiency and high infant mortality in northern Laos.

Directory of Open Access Journals (Sweden)

Hubert Barennes

2015-03-01

Full Text Available Infantile beriberi (thiamine deficiency occurs mainly in infants breastfed by mothers with inadequate intake of thiamine, typically among vulnerable populations. We describe possible and probable cases of infantile thiamine deficiency in northern Laos.Three surveys were conducted in Luang Namtha Province. First, we performed a retrospective survey of all infants with a diagnosis of thiamine deficiency admitted to the 5 hospitals in the province (2007-2009. Second, we prospectively recorded all infants with cardiac failure at Luang Namtha Hospital. Third, we further investigated all mothers with infants (1-6 months living in 22 villages of the thiamine deficiency patients' origin. We performed a cross-sectional survey of all mothers and infants using a pre-tested questionnaire, physical examination and squat test. Infant mortality was estimated by verbal autopsy. From March to June 2010, four suspected infants with thiamine deficiency were admitted to Luang Namtha Provincial hospital. All recovered after parenteral thiamine injection. Between 2007 and 2009, 54 infants with possible/probable thiamine deficiency were diagnosed with acute severe cardiac failure, 49 (90.2% were cured after parenteral thiamine; three died (5.6%. In the 22 villages, of 468 live born infants, 50 (10.6%, 95% CI: 8.0-13.8 died during the first year. A peak of mortality (36 deaths was reported between 1 and 3 months. Verbal autopsy suggested that 17 deaths (3.6% were due to suspected infantile thiamine deficiency. Of 127 mothers, 60 (47.2% reported edema and paresthesia as well as a positive squat test during pregnancy; 125 (98.4% respected post-partum food avoidance and all ate polished rice. Of 127 infants, 2 (1.6% had probable thiamine deficiency, and 8 (6.8% possible thiamine deficiency.Thiamine deficiency may be a major cause of infant mortality among ethnic groups in northern Laos. Mothers' and children's symptoms are compatible with thiamine deficiency. The severity

Gastric emptying in patients with vitamin B{sub 12} deficiency

Energy Technology Data Exchange (ETDEWEB)

Yagci, Muenci; Yamac, Kadri; Acar, Kadir; Haznedar, Rauf [Department of Hematology, Gazi Medical School (Turkey); Cingi, Elif; Kitapci, Mehmet [Department of Nuclear Medicine, Gazi Medical School (Turkey)

2002-09-01

The clinical presentation of patients with vitamin B{sub 12} deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B{sub 12} deficiency. The aim of this study was to evaluate the effect of vitamin B{sub 12} deficiency on autonomic nervous system function by studying gastric emptying times (T{sub 1/2}). Twenty patients with newly diagnosed vitamin B{sub 12} deficiency and 12 control patients with gastritis and normal vitamin B{sub 12} levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B{sub 12} replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T{sub 1/2} in patients before and after treatment and in controls were 103.83{+-}48.80 min, 90.00{+-}17.29 min and 74.55{+-}8.52 min, respectively. The difference in mean gastric emptying T{sub 1/2} between patients before treatment and controls was statistically significant (P<0.01). The statistically significant difference persisted after vitamin B{sub 12} treatment (P<0.05), though mean gastric emptying T{sub 1/2} was somewhat shorter. There were no positive or negative correlations between gastric emptying T{sub 1/2} and the following parameters: haemoglobin, vitamin B{sub 12} level and Helicobacter pylori positivity. In conclusion, gastric emptying T{sub 1/2} was prolonged in patients with vitamin B{sub 12} deficiency and this prolongation was not corrected after vitamin B{sub 12} replacement therapy. Although autonomic nervous system dysfunction due to vitamin B{sub 12} deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon

Advisory Committee on human radiation experiments. Final report, Supplemental Volume 2. Sources and documentation

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-01-01

This volume and its appendixes supplement the Advisory Committee`s final report by reporting how we went about looking for information concerning human radiation experiments and intentional releases, a description of what we found and where we found it, and a finding aid for the information that we collected. This volume begins with an overview of federal records, including general descriptions of the types of records that have been useful and how the federal government handles these records. This is followed by an agency-by-agency account of the discovery process and descriptions of the records reviewed, together with instructions on how to obtain further information from those agencies. There is also a description of other sources of information that have been important, including institutional records, print resources, and nonprint media and interviews. The third part contains brief accounts of ACHRE`s two major contemporary survey projects (these are described in greater detail in the final report and another supplemental volume) and other research activities. The final section describes how the ACHRE information-nation collections were managed and the records that ACHRE created in the course of its work; this constitutes a general finding aid for the materials deposited with the National Archives. The appendices provide brief references to federal records reviewed, descriptions of the accessions that comprise the ACHRE Research Document Collection, and descriptions of the documents selected for individual treatment. Also included are an account of the documentation available for ACHRE meetings, brief abstracts of the almost 4,000 experiments individually described by ACHRE staff, a full bibliography of secondary sources used, and other information.

Iron deficiency anaemia: with the conclusion of a need for iron reader

Science.gov (United States)

Lim, Wai Feng; Yap, Boon Kar; Lai, Mei I.; Talik, Noorazrina; Nasser, Ammar Ahmed; Al-Haiqi, Ahmed Mubarak Ahmed; Sankar Krishnan, Prajindra

2017-10-01

In our bloodstream, there are plenty of red blood cells (RBC), which function as an important oxygen carrier in our bodies. Each RBC consists of millions of haemoglobin (Hb), which is made up from globin and iron. If any deficiency/malfunction of any globin, it will lead to anaemia as indicated in low Hb level while iron deficiency anaemia (IDA) is anaemic due to the lacking of iron as indicated in low Hb and ferritin levels. IDA affects almost two billion people globally while anaemia without iron deficiency, such as thalassaemia, affects almost 4.5% in Malaysian population. These anaemic conditions have similar clinical symptoms like fatigue, dizziness, in which disturb their cognitive development and productivity in workplace. In areas without proper medical access, many anaemic individuals were misdiagnosed and treated with iron tablets because they were thought to have iron deficiency anaemia due to low Hb content. But, excess iron is toxic to the body. Misdiagnosis can be avoided by iron status assessment. We hereby review the currently available iron status parameters in laboratory and field study with the conclusion of demonstrating the importance of a need for iron reader, in the effort to reduce the prevalence of IDA globally.

Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

Science.gov (United States)

Ahmad, Shadab; Basak, Trayambak; Anand Kumar, K; Bhardwaj, Gourav; Lalitha, A; Yadav, Dilip K; Chandak, Giriraj Ratan; Raghunath, Manchala; Sengupta, Shantanu

2015-09-08

Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway. In this study, using similar approach, we identified 26 differentially expressed proteins in the kidney of pups born to mothers fed with vitamin B12 deficient diet while only four proteins were identified in the folate deficient group. Importantly, proteins like calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in the functioning of the kidney were upregulated in B12 deficient group. Our results hint towards a larger effect of vitamin B12 deficiency compared to that of folate presumably due to greater elevation of homocysteine in vitamin B12 deficient group. In view of widespread vitamin B12 and folate deficiency and its association with several diseases like anemia, cardiovascular and renal diseases, our results may have large implications for kidney diseases in populations deficient in vitamin B12 especially in vegetarians and the elderly people.This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?

Science.gov (United States)

Pawlak, Roman

2015-06-01

The goal of this paper is to describe the role of vitamin B12 deficiency in cardiovascular disease development among vegetarians. Vegetarians have a high prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated with a variety of atherogenic processes that are mainly, but not exclusively, due to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. Mean homocysteine concentration >10 μmol/L among vegetarians was reported in 32 of 34 reports. Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems. Compared with non-vegetarians, vegetarians have an improved profile of the traditional cardiovascular disease risk factors, including serum lipids, blood pressure, serum glucose concentration, and weight status. However, not all studies that assessed cardiovascular disease incidence among vegetarians reported a protective effect. Among studies that did show a lower prevalence of circulatory health problems, the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. In order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

Science.gov (United States)

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-03-28

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

Carnitine Deficiency and Pregnancy

Directory of Open Access Journals (Sweden)

Anouk de Bruyn

2015-01-01

Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

Omega-3 deficiency impairs honey bee learning

Science.gov (United States)

Arien, Yael; Dag, Arnon; Zarchin, Shlomi; Masci, Tania

2015-01-01

Deficiency in essential omega-3 polyunsaturated fatty acids (PUFAs), particularly the long-chain form of docosahexaenoic acid (DHA), has been linked to health problems in mammals, including many mental disorders and reduced cognitive performance. Insects have very low long-chain PUFA concentrations, and the effect of omega-3 deficiency on cognition in insects has not been studied. We show a low omega-6:3 ratio of pollen collected by honey bee colonies in heterogenous landscapes and in many hand-collected pollens that we analyzed. We identified Eucalyptus as an important bee-forage plant particularly poor in omega-3 and high in the omega-6:3 ratio. We tested the effect of dietary omega-3 deficiency on olfactory and tactile associative learning of the economically highly valued honey bee. Bees fed either of two omega-3–poor diets, or Eucalyptus pollen, showed greatly reduced learning abilities in conditioned proboscis-extension assays compared with those fed omega-3–rich diets, or omega-3–rich pollen mixture. The effect on performance was not due to reduced sucrose sensitivity. Omega-3 deficiency also led to smaller hypopharyngeal glands. Bee brains contained high omega-3 concentrations, which were only slightly affected by diet, suggesting additional peripheral effects on learning. The shift from a low to high omega-6:3 ratio in the Western human diet is deemed a primary cause of many diseases and reduced mental health. A similar shift seems to be occurring in bee forage, possibly an important factor in colony declines. Our study shows the detrimental effect on cognitive performance of omega-3 deficiency in a nonmammal. PMID:26644556

A rare cause of anemia due to upper gastrointestinal bleeding: Cameron lesion

Directory of Open Access Journals (Sweden)

Ismet Özaydın

2014-01-01

Full Text Available Asymptomatic large hiatal hernias may lead to iron deficiency anemia due to occult and massive bleeding from linear gastric erosions or ulcers on the mucosal folds at the level of the diaphragm called the Cameron lesions. The diagnosis is usually made during upper gastrointestinal system endoscopies. Current therapy includes the medication with proton pump inhibitors in combination with oral iron supplements and in some cases surgical reconstruction of hiatal hernia with fundoplication. We present a case of a 78-year-old woman who was admitted to the outpatient clinic with the diagnosis of iron deficiency anemia without signs of acute gastrointestinal bleeding. She was treated with medication and her follow-up gastroscopy showed a total cure. She is asymptomatic for two years after treatment with proton pump inhibitors and iron supplements. Cameron lesions should be kept in mind as an unusual cause of iron deficiency anemia due to gastrointestinal bleeding. 

A study of the zinc deficiency in a section of rural people in Bengal ...

African Journals Online (AJOL)

kemrilib

in India is due to lipid toxicity of unsaturated fats used for cooking [8]. ... suffer from chronic energy deficiency due to low fat intake. This condition is ..... pancreatic diabetes, Experimental Clinical ... The preferred metabolic pathway from linoleic.

The story of iodine deficiency: An international challenge in nutrition

International Nuclear Information System (INIS)

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

The story of iodine deficiency: An international challenge in nutrition

Energy Technology Data Exchange (ETDEWEB)

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.

[Glucose-6-phosphate dehydrogenase deficiency in children: a case report].

Science.gov (United States)

Verdugo L, Patricia; Calvanese T, Marlene; Rodríguez V, Diego; Cárcamo C, Cassandra

2014-02-01

Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed. To analyze the case of a child who presented hemolytic crisis due to favism. A 2 year and 7 month old boy with a history of hyperbilirubinemia during the newborn period with no apparent cause, no family history of hemolytic anemia or parental consanguinity. He presented a prolonged neonatal jaundice and severe anemia requiring RBC transfusion. An intake of fava beans 48 h prior to onset of symptoms was reported. G6PD qualitative determination was compatible with this enzyme deficiency. G6PD deficiency can be highly variable in its clinical presentation, so it is necessary to keep it in mind during the diagnosis of hemolytic anemia at any age.

Iron-Deficiency Anemia (For Parents)

Science.gov (United States)

... Videos for Educators Search English Español Iron-Deficiency Anemia KidsHealth / For Parents / Iron-Deficiency Anemia What's in ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

Neuroimmune interactions in Sjögren's syndrome: relationship of exocrine gland dysfunction with autoantibodies to muscarinic acetylcholine receptor-3 and mental health status parameters.

Science.gov (United States)

Deák, Magdolna; Szvetnik, Attila; Balog, Attila; Sohár, Nicolette; Varga, Renáta; Pokorny, Gyula; Tóth, Gábor; Kiss, Mária; Kovács, László

2013-01-01

Antimuscarinic acetylcholine receptor-3 (m3AChR) autoantibodies have been described in primary Sjögren's syndrome (pSS). The aim of this study was to compare various methods for their detection and to assess the contributions of anti-m3AChR and other immunological and psychosocial factors to the pathomechanism of secondary SS (sSS). Sixty-five rheumatoid arthritis (RA) patients, 103 systemic lupus erythematosus (SLE) patients, 76 pSS patients and 50 controls were compared. Three immunodominant epitopes of m3AChR were synthesized and used in ELISA. Two extracellular epitopes were also prepared in fusion with glutathione-S-transferase and one in conjugation with bovine serum albumin. Mental health status was assessed with the 36-item Short-Form Health Survey and Functional Assessment of Chronic Illness Therapy fatigue scale. Correlations were evaluated between glandular function and anti-m3AChR positivities and specificities, features of SLE and RA, and mental health parameters. Fourteen RA and 27 SLE patients had sSS. The autoantibody levels to all epitopes of m3AChR were significantly higher in pSS and SLE patients than in the controls. The fusion protein forms discriminated RA from pSS and SLE; furthermore, the YNIP fusion protein also distinguished pSS from SLE. The prevalence and the mean levels of all autoantibodies did not differ statistically between sicca and non-sicca SLE or RA patients. Glandular dysfunction correlated with higher age in SLE and RA and an impaired health-related quality of life in SLE. The second and third extracellular loops of m3AChR are antigenic in pSS. Immunoassays with antigens as fusion peptides demonstrate the best performance. Sicca SLE patients have worse mental health status. Anti-m3AChR antibodies represent a peculiar example of neuroimmune interactions. Copyright © 2012 S. Karger AG, Basel.

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

LENUS (Irish Health Repository)

Marshall, C

2012-02-03

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

Iron deficiency and cognitive functions

Directory of Open Access Journals (Sweden)

Jáuregui-Lobera I

2014-11-01

Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

Psychomotor retardation in a girl with complete growth hormone deficiency.

Science.gov (United States)

Dayal, Devi; Malhi, Prabhjot; Kumar Bhalla, Anil; Sachdeva, Naresh; Kumar, Rakesh

2013-01-01

Infants with complete growth hormone deficiency may suffer from psychomotor retardation in addition to severe growth failure. Without replacement therapy, they may have a compromised intellectual potential manifesting as learning disabilities and attention-deficit disorders in later life. In this communication, we discuss an infant who showed improvement in physical growth after growth hormone therapy but her psychomotor skills did not improve probably due to late start of treatment. There is a need to start growth hormone therapy as early as possible in infants with complete growth hormone deficiency to avoid adverse effects on psychomotor and brain development.

Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project.

Science.gov (United States)

Prior, Nieves; Remor, Eduardo; Gómez-Traseira, Carmen; López-Serrano, Concepción; Cabañas, Rosario; Contreras, Javier; Campos, Ángel; Cardona, Victoria; Cimbollek, Stefan; González-Quevedo, Teresa; Guilarte, Mar; de Rojas, Dolores Hernández Fernández; Marcos, Carmen; Rubio, María; Tejedor-Alonso, Miguel Ángel; Caballero, Teresa

2012-07-20

There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains. To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.

Iron Refractory Iron Deficiency Anaemia: A Rare Cause of Iron Deficiency Anaemia

LENUS (Irish Health Repository)

McGrath, T

2018-01-01

We describe the case of a 17-month-old boy with a hypochromic microcytic anaemia, refractory to oral iron treatment. After exclusion of dietary and gastrointestinal causes of iron deficiency, a genetic cause for iron deficiency was confirmed by finding two mutations in the TMPRSS6 gene, consistent with a diagnosis of iron-refractory iron deficiency anaemia (IRIDA).

Deficiency of the Chemotactic Factor Inactivator in Human Sera with α1-Antitrypsin Deficiency

Science.gov (United States)

Ward, Peter A.; Talamo, Richard C.

1973-01-01

As revealed by appropriate fractionation procedures, human serum deficient in α1-antitrypsin (α1-AT) is also deficient in the naturally occurring chemotactic factor inactivator. These serum donors had severe pulmonary emphysema. Serum from patients with clinically similar pulmonary disease, but with presence of α1-AT in the serum, showed no such deficiency of the chemotactic factor inactivator. When normal human serum and α1-AT-deficient human sera are chemotactically activated by incubation with immune precipitates, substantially more chemotactic activity is generated in α1-AT-deficient serum. These data indicate that in α1-AT-deficient serum there is an imbalance in the generation and control of chemotactic factors. It is suggested that the theory regarding development of pulmonary emphysema in patients lacking the α1-antitrypsin in their serum should be modified to take into account a deficiency of the chemotactic factor inactivator. PMID:4683887

Iron-Deficiency Anemia

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Full Text Available ... your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ...

Iron-Deficiency Anemia

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Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

Fire Safety Deficiencies

Data.gov (United States)

U.S. Department of Health & Human Services — A list of all fire safety deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection...

ECONOMICAL BASIS TO ADDRESS MICRONUTRIENT DEFICIENCIES IN DEVELOPING WORLD

Directory of Open Access Journals (Sweden)

Amirul Hassan

2015-01-01

Full Text Available Malnutrition has been called by economists at the World Bank as the “non-human face” of poverty,1 Adults who were malnourished as children earn at least 20% less on average than those who weren’t , 2.Malnutrition is often caused by underlying economics, i.e. the lack of money. Economics is very important in regards to malnutrition; it allows an individual to purchase nutrients. In many places around the world, a lack of money prevents the purchase of a variety of foods. The lack in variety usually leads to micronutrient malnutrition. Economics also decides the production of food in all countries around the world and the ability of a country to overcome difficult times. Thus economics affects ALL people at ALL levels of society, 3.Micronutrient deficiencies also known as ‘hidden hunger’ are determining and aggravating factors for health status and quality of life. It is estimated half of anaemia cases are due to iron deficiency , 4.  Almost half of children in low- and middle-income countries – 47% of under-fives are affected by anaemia, impairing cognitive and physical development,5. Iodine deficiency is the greatest single cause of mental retardation and brain damage. Coincidently,  the number of countries in which iodine-deficiency disorders were considered a public health concern reduced by 43% between 1993 and 2007,6.  Zinc deficiency affects children’s health and physical growth; it is also essential for mothers during pregnancy. It is estimated to cause 4% of deaths in pre-school aged children in lower-income countries. 7 . The Global Burden of Disease estimates showed that among the 26 major risk factors of the global burden of disease,8 iron deficiency ranks ninth overall, zinc deficiency is eleventh, and vitamin A deficiency, is thirteenth. Annually each developing country of the world are losing over millions or billions US $ in Gross Domestic Product (GDP to vitamins and minerals deficiencies. But scaling up core

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such ...

Factor VII deficiency

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

Extracellular matrix organization in developing muscle: correlation with acetylcholine receptor aggregates.

Science.gov (United States)

Bayne, E K; Anderson, M J; Fambrough, D M

1984-10-01

Monoclonal antibodies recognizing laminin, heparan sulfate proteoglycan, fibronectin, and two apparently novel connective tissue components have been used to examine the organization of extracellular matrix of skeletal muscle in vivo and in vitro. Four of the five monoclonal antibodies are described for the first time here. Immunocytochemical experiments with frozen-sectioned muscle demonstrated that both the heparan sulfate proteoglycan and laminin exhibited staining patterns identical to that expected for components of the basal lamina. In contrast, the remaining matrix constituents were detected in all regions of muscle connective tissue: the endomysium, perimysium, and epimysium. Embryonic muscle cells developing in culture elaborated an extracellular matrix, each antigen exhibiting a unique distribution. Of particular interest was the organization of extracellular matrix on myotubes: the build-up of matrix components was most apparent in plaques overlying clusters of an integral membrane protein, the acetylcholine receptor (AChR). The heparan sulfate proteoglycan was concentrated at virtually all AChR clusters and showed a remarkable level of congruence with receptor organization; laminin was detected at 70-95% of AChR clusters but often was not completely co-distributed with AChR within the cluster; fibronectin and the two other extracellular matrix antigens occurred at approximately 20, 8, and 2% of the AChR clusters, respectively, and showed little or no congruence with AChR. From observations on the distribution of extracellular matrix components in tissue cultured fibroblasts and myogenic cells, several ideas about the organization of extracellular matrix are suggested. (a) Congruence between AChR clusters and heparan sulfate proteoglycan suggests the existence of some linkage between the two molecules, possibly important for regulation of AChR distribution within the muscle membrane. (b) The qualitatively different patterns of extracellular matrix

Anemia, Iron Deficiency and Iodine Deficiency among Nepalese School Children.

Science.gov (United States)

Khatiwada, Saroj; Lamsal, Madhab; Gelal, Basanta; Gautam, Sharad; Nepal, Ashwini Kumar; Brodie, David; Baral, Nirmal

2016-07-01

To assess iodine and iron nutritional status among Nepalese school children. A cross-sectional, community based study was conducted in the two districts, Ilam (hilly region) and Udayapur (plain region) of eastern Nepal. A total of 759 school children aged 6-13 y from different schools within the study areas were randomly enrolled. A total of 759 urine samples and 316 blood samples were collected. Blood hemoglobin level, serum iron, total iron binding capacity and urinary iodine concentration was measured. Percentage of transferrin saturation was calculated using serum iron and total iron binding capacity values. The mean level of hemoglobin, serum iron, total iron binding capacity, transferrin saturation and median urinary iodine excretion were 12.29 ± 1.85 g/dl, 70.45 ± 34.46 μg/dl, 386.48 ± 62.48 μg/dl, 19.94 ± 12.07 % and 274.67 μg/L respectively. Anemia, iron deficiency and iodine deficiency (urinary iodine excretion iron deficient children. Iron deficiency and anemia are common in Nepalese children, whereas, iodine nutrition is more than adequate. Low urinary iodine excretion was common in iron deficiency and anemia.

Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding

DEFF Research Database (Denmark)

Dahlerup, Jens Frederik; Eivindson, Martin; Jacobsen, Bent Ascanius

2015-01-01

A general overview is given of the causes of anemia with iron deficiency as well as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia with iron deficiency but without overt GI bleeding is associated with a risk of malignant disease of the gastrointestinal tract; upper...... gastrointestinal cancer is 1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations. The following diagnostic strategy is recommended...... for unexplained anemia with iron deficiency: conduct serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing and perform bidirectional endoscopy (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in premenopausal women

Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice.

Science.gov (United States)

Lambert, G; Sakai, N; Vaisman, B L; Neufeld, E B; Marteyn, B; Chan, C C; Paigen, B; Lupia, E; Thomas, A; Striker, L J; Blanchette-Mackie, J; Csako, G; Brady, J N; Costello, R; Striker, G E; Remaley, A T; Brewer, H B; Santamarina-Fojo, S

2001-05-04

To evaluate the biochemical and molecular mechanisms leading to glomerulosclerosis and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density lipoprotein receptor (LDLr) KO, and cholesteryl ester transfer protein transgenic mice. LCAT-KO mice had normochromic normocytic anemia with increased reticulocyte and target cell counts as well as decreased red blood cell osmotic fragility. A subset of LCAT-KO mice accumulated lipoprotein X and developed proteinuria and glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli. LCAT deficiency reduced the plasma high density lipoprotein (HDL) cholesterol (-70 to -94%) and non-HDL cholesterol (-48 to -85%) levels in control, apoE-KO, LDLr-KO, and cholesteryl ester transfer protein-Tg mice. Transcriptome and Western blot analysis demonstrated up-regulation of hepatic LDLr and apoE expression in LCAT-KO mice. Despite decreased HDL, aortic atherosclerosis was significantly reduced (-35% to -99%) in all mouse models with LCAT deficiency. Our studies indicate (i) that the plasma levels of apoB containing lipoproteins rather than HDL may determine the atherogenic risk of patients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role for lipoproteins X in the development of glomerulosclerosis in LCAT deficiency. The availability of LCAT-KO mice characterized by lipid, hematologic, and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulosclerosis in LCAT-deficient states.

Iron-Deficiency Anemia

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Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People ...

Iron-Deficiency Anemia

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Full Text Available ... view the colon directly. What if my doctor thinks something else is causing my iron-deficiency anemia? ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

Iron-Deficiency Anemia

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Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. ...

Iron-Deficiency Anemia

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Full Text Available ... iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as celiac disease; inflammatory bowel diseases, ... iron-deficiency anemia , such as bleeding in the digestive or urinary tract or heavy menstrual bleeding, your ...

Iron-Deficiency Anemia

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Full Text Available ... mg and women need 18 mg. After age 51, both men and women need 8 mg. Pregnant ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

Iron-Deficiency Anemia

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Full Text Available ... fatigue or tiredness, shortness of breath, or chest pain. If your doctor diagnoses you with iron-deficiency ... Common symptoms of iron-deficiency anemia include: Chest pain Coldness in the hands and feet Difficulty concentrating ...

Iron-Deficiency Anemia

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Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

Iron-Deficiency Anemia

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Full Text Available ... conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

Iron-Deficiency Anemia

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Full Text Available ... learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

Iron-Deficiency Anemia

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Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

Iron-Deficiency Anemia

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Full Text Available ... leaving cells where it is stored or from being absorbed in the duodenum, the first part of ... treatments for iron-deficiency anemia. Living With After being diagnosed with iron-deficiency anemia, it is important ...

Iron-Deficiency Anemia

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Full Text Available ... iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research that ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

Conducting financial due diligence of medical practices.

Science.gov (United States)

Louiselle, P

1995-12-01

Many healthcare organizations are acquiring medical practices in an effort to build more integrated systems of healthcare products and services. This acquisition activity must be approached cautiously to ensure that medical practices being acquired do not have deficiencies that would jeopardize integration efforts. Conducting a thorough due diligence analysis of medical practices before finalizing the transaction can limit the acquiring organizations' legal and financial exposure and is a necessary component to the acquisition process. The author discusses the components of a successful financial due diligence analysis and addresses some of the risk factors in a practice acquisition.

Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms

Science.gov (United States)

Phillips, William D.; Vincent, Angela

2016-01-01

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms. PMID:27408701

Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms.

Science.gov (United States)

Phillips, William D; Vincent, Angela

2016-01-01

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

William D. Phillips

2016-06-01

Full Text Available Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (IgG1 and IgG3 antibodies to the acetylcholine receptor (AChR. They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK, or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4, are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

Iron-Deficiency Anemia

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Full Text Available ... en español Iron-deficiency anemia is a common type of anemia that occurs if you do not ... iron-deficiency anemia and help rule out other types of anemia. Treatment will explain treatment-related complications ...

Iron-Deficiency Anemia

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Full Text Available ... other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... check the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

Iron-Deficiency Anemia

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Full Text Available ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

Study of Neutron-Deficient $^{202-205}$Fr Isotopes with Collinear Resonance Ionization Spectroscopy

CERN Document Server

De Schepper, Stijn; Cocolios, Thomas; Budincevic, Ivan

The scope of this master’s thesis is the study of neutron-deficient $^{202−205}$Fr isotopes. These isotopes are inside the neutron-deficient lead region, a region that has shown evidence of shape coexistence. For this thesis, this discussion is limited to the phenomenon where a low lying excited state has a different shape than the ground state. Shape coexistence is caused by intruder states. These are single-particle Shell Model states that are perturbed in energy due to the interaction with a deformed core. In the neutron-deficient lead region the main proton intruder orbit is the 3s$_{1/2}$orbit. When going towards more neutron-deficient isotopes, deformation increases. The $\\pi3s_{1/2}$orbit will rise in energy and will eventually become the ground state in odd- A bismuth (Z=83) isotopes. It is also observed in odd-A astatine (Z=85) isotopes, already in less neutron-deficient nuclei. The same phenomenon is expected to be present francium (Z=87) isotopes already at $^{199}$Fr. Although it is currently ...

Iron-Deficiency Anemia

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Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to iron-deficiency anemia ... daily amount of iron. If you have other medical conditions that cause iron-deficiency anemia , such as ...

Iron-Deficiency Anemia

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Full Text Available ... anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for ...

Iron-Deficiency Anemia

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Full Text Available ... loss and lead to iron-deficiency anemia. Common causes of blood loss that lead to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular use of medicines such as aspirin ...

Iron-Deficiency Anemia

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Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ...

Iron-Deficiency Anemia

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Full Text Available ... anemia. Return to Signs, Symptoms, and Complications to review signs and symptoms as well as complications from iron-deficiency ... NIH]) Heavy Menstrual Bleeding (Centers for Disease Control and ... Dietary Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library ...

Iron-Deficiency Anemia

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Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, ... you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, constipation, or upset stomach. ...

Iron-Deficiency Anemia

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Full Text Available ... how we are using current research and advancing research to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

The phenomenon of micronutrient deficiency among children in China: a systematic review of the literature.

Science.gov (United States)

Wong, Angel Y S; Chan, Esther W; Chui, Celine S L; Sutcliffe, Alastair G; Wong, Ian C K

2014-11-01

The present study aimed to review the literature on micronutrient deficiency and other factors influencing a deficiency status among children living in China. A systematic review was performed to analyse the literature. Studies were identified through a search of PubMed and secondary references. Children living in China aged less than 18 years. Sixty-one articles were included. The prevalence of vitamin A deficiency decreased to approximately 10 % in 1995-2009. It increased with age but no significant difference was found between genders. The prevalence of thiamin and vitamin B12 deficiency was 10·5 % in Yunnan and 4·5 % in Chongqing provinces, respectively. Higher vitamin D deficiency rates were seen in spring and winter. The incidence of bleeding due to vitamin K deficiency was 3·3 % in 1998-2001 and more prevalent in rural areas. Both iodine deficiency and excess iodine intake were observed. Goitre rates were reported in Tibet, Jiangxi, Gansu and Hong Kong (3·5-46 %). Anaemia rates ranged from 20 % to 40 % in 2007-2011. High Se deficiency rates were found in Tibet, Shaanxi and Jiangsu. High Zn deficiency rates were also found (50-70 %) in 1995-2006. Few studies reported Ca deficiency rates (19·6-34·3 %). The degrees of deficiency for vitamin A, vitamin B12, Fe and Zn were more substantial in rural areas compared with urban areas. The prevalence of micronutrient deficiency rates varied. Socio-economic status, environmental factors and the Chinese diet may influence micronutrient deficiency. Public health policies should consider implementing programmes of supplementation, food fortification and nutrition education to address these deficiencies among Chinese children.

Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?

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Moreno-Reyes Rodrigo

2009-04-01

Full Text Available Abstract Background About 20–30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation. Presentation of the hypothesis We hypothesize that low availability of 1,25-dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in the vitamin D receptor or in its activating/inactivating enzymes, contributes to the appearance of IRIS. Furthermore, drug interactions with the enzymatic pathways of vitamin D could favour the development of IRIS. Testing the hypothesis Our hypothesis could be explored by a case-control study to assess the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral treatment who develop and do not develop IRIS. Implications of the hypothesis If the role of vitamin D in IRIS is confirmed, we would be able to screen patients at risk for IRIS by screening for vitamin D deficiency. After confirmation by means of a clinical trial, vitamin D supplementation could be a cheap and safe way to reduce the incidence of IRIS.

Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

Science.gov (United States)

Cerbone, Manuela; Dattani, Mehul T

2017-12-01

Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary hormone deficits, with TSH deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary hormone deficiencies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Procaine rapidly inactivates acetylcholine receptors from Torpedo and competes with agonist for inhibition sites

International Nuclear Information System (INIS)

Forman, S.A.; Miller, K.W.

1989-01-01

The relationship between the high-affinity procaine channel inhibition site and the agonist self-inhibition site on acetylcholine receptors (AChRs) from Torpedo electroplaque was investigated by using rapid 86 Rb + quenched-flux assays at 4 degree C in native AChR-rich vesicles on which 50-60% of ACh activation sites were blocked with α-bungarotoxin (α-BTX). In the presence of channel-activating acetylcholine (ACh) concentrations alone, AChR undergoes one phase of inactivation in under a second. Addition of procaine produces two-phase inactivation similar to that seen with self-inhibiting ACh concentrations rapid inactivation complete in 30-75 ms is followed by fast desensitization at the same k d observed without procaine. The dependence of k r on [procaine] is consistent with a bimolecular association between procaine and its AChR site. Inhibition of AChR function by mixtures of procaine plus self-inhibiting concentrations of ACh or suberyldicholine was studied by reducing the level of α-BTX block in vesicles. The data support a mechanism where procaine binds preferentially to the open-channel AChR state, since no procaine-induced inactivation is observed without agonist and k r 's dependence on [ACh] in channel-activating range closely parallels that of 86 Rb + flux response to ACh

Study of asymmetric fission yield behavior from neutron-deficient Hg isotope

International Nuclear Information System (INIS)

Perkasa, Y. S.; Waris, A.; Kurniadi, R.; Su'ud, Z.

2014-01-01

A study of asymmetric fission yield behavior from a neutron-deficient Hg isotope has been conducted. The fission yield calculation of the neutron-deficient Hg isotope using Brownian Metropolis shape had showed unusual result at decreasing energy. In this paper, this interesting feature will be validated by using nine degree of scission shapes parameterization from Brosa model that had been implemented in TALYS nuclear reaction code. This validation is intended to show agreement between both model and the experiment result. The expected result from these models considered to be different due to dynamical properties that implemented in both models

MicroRNA regulatory mechanisms on Citrus sinensis leaves to magnesium-deficiency

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Cui-Lan eMa

2016-03-01

Full Text Available Magnesium (Mg-deficiency, which affects crop productivity and quality, widespreadly exists in many agricultural crops, including citrus. However, very limited data are available on Mg-deficiency-responsive microRNAs (miRNAs in higher plants. Using Illumina sequencing, we isolated 75 (73 known and 2 novel up- and 71 (64 known and 7 novel down-regulated miRNAs from Mg-deficient Citrus sinensis leaves. In addition to the remarkable metabolic flexibility as indicated by the great alteration of miRNA expression, the adaptive responses of leaf miRNAs to Mg-deficiency might also involve the following several aspects: (a up-regulating stress-related genes by down-regulating miR164, miR7812, miR5742, miR3946 and miR5158; (b enhancing cell transport due to decreased expression of miR3946 and miR5158 and increased expression of miR395, miR1077, miR1160 and miR8019; (c activating lipid metabolism-related genes by repressing miR158, miR5256 and miR3946; (d inducing cell wall-related gene expansin 8A by repressing miR779; and (e down-regulating the expression of genes involved in the maintenance of S, K and Cu by up-regulating miR395 and miR6426. To conclude, we isolated some new known miRNAs (i.e., miR7812, miR8019, miR6218, miR1533, miR6426, miR5256, miR5742, miR5561, miR5158 and miR5818 responsive to nutrient deficiencies and found some candidate miRNAs that might contribute to Mg-deficiency tolerance. Therefore, our results not only provide novel information about the responses of plant to Mg-deficiency, but also are useful for obtaining the key miRNAs for plant Mg-deficiency tolerance.

Trace element deficiency and its diagnosis by biochemical criteria

International Nuclear Information System (INIS)

Kirchgessner, M.; Grassmann, E.; Roth, H.P.; Spoerl, R.; Schnegg, A.

1976-01-01

The effect of trace element deficiency on growth of rats and dairy cows is demonstrated using zinc and nickel. The effect of copper deficiency on reproductive performance is shown to be associated with increased death rates of pregnant animals and their foetuses. For the diagnosis of suboptimum states of trace element supply, biochemical criteria are needed. The mere analysis of the trace element content of various body tissues may lead to falase diagnoses because of the often slow response to varying intake and because of interactions with other dietary ingredients affecting absorption and metabolic efficiency of utilization. Thus copper deficiency is associated with a decrease in the serum level of both copper and iron, despite adequate iron intake, and simultaneously with an accumulation of iron in the liver of the animal. Enzymes and hormones containing the essential trace element as an integral constituent may serve as biochemical criteria. A sensitive response to zinc intake is exhibited by the activity of the alkaline phosphatase of serum or bones, and by the activity of the pancreatic carboxypeptidase A, all of which show a significant reaction to deficient intake within two to four days, and perhaps by the biopotency of insulin. Ceruloplasmin responds to the supply of copper. Its biosynthesis in the liver is possible only from copper available for this purpose. Thus, the determination of ceruloplasmin may take account of at least part of the copper available to the body for metabolic functions. Among various criteria, the catalase activity in blood may provide additional information on the state of iron supply. Malate dehydrogenase and glucose-6-phosphate dehydrogenase respond to nickel-deficient intake. Nickel deficiency also involves anaemia due to disorders in iron absorption

Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

Science.gov (United States)

Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

2015-01-01

Abstract Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron. PMID:26061331

Iron-Deficiency Anemia

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Full Text Available ... exploring about iron-deficiency anemia. Read more New treatments for disorders that lead to iron-deficiency anemia. We are ... and other pathways. This could help develop new therapies for conditions that ... behavior, thinking, and mood during adolescence. Treating anemia in ...

Nutritional iron deficiency

NARCIS (Netherlands)

Zimmermann, M.B.; Hurrell, R.F.

2007-01-01

Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

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

Directory of Open Access Journals (Sweden)

Raffaele Nardone

2013-01-01

Full Text Available 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.

The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

DEFF Research Database (Denmark)

Liszewski, Walter; Gniadecki, Robert

2016-01-01

due to a downregulation or absence of cytokines. Here, we review the diagnosis and clinical management of cytokine deficiency syndromes in dermatology. We will review the biology of cytokines, and the current approved indications for recombinant cytokines and anticytokine antibodies. We will also...

Anemia Due to Excessive Bleeding

Science.gov (United States)

... Hemolytic Anemia Hemoglobin C, S-C, and E Diseases Iron Deficiency Anemia Sickle Cell Disease Thalassemias Vitamin Deficiency Anemia (See ... Hemolytic Anemia Hemoglobin C, S-C, and E Diseases Iron Deficiency Anemia Sickle Cell Disease Thalassemias Vitamin Deficiency Anemia NOTE: ...

Baraitser and Winter syndrome with growth hormone deficiency.

Science.gov (United States)

Chentli, Farida; Zellagui, Hadjer

2014-01-01

Baraitser-Winter syndrome (BWS), first reported in 1988, is apparently due to genetic abnormalities that are still not well-defined, although many gene abnormalities are already discovered and de novo missense changes in the cytoplasmic actin-encoding genes (called ACTB and ACTG1) have been recently discovered. The syndrome combines facial and cerebral malformations. Facial malformations totally or partially present in the same patient are: Iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, and prominent epicanthic folds. The various brain malformations are probably responsible for growth and mental retardation. To the best of our knowledge, the syndrome is very rare as few cases have been reported so far. Our aim was to describe a child with a phenotype that looks like BWS with proved partial growth hormone (GH) deficiency which was not reported before. A girl aged 7-year-old of consanguineous parents was referred for short stature and mental retardation. Clinical examination showed dwarfism and a delay in her mental development. Other clinical features included: Strabismus, epicanthic folds, broad nasal bridge, and brain anomalies such as lissencephaly, bilateral hygroma, and cerebral atrophy. Hormonal assessment showed partial GH deficiency without other endocrine disorders. Our case looks exactly like BWS. However, apart from facial and cerebral abnormalities, there is a partial GH deficiency which can explain the harmonious short stature. This case seems worth to be reported as it adds GH deficiency to the very rare syndrome.

Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

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Claudia A Montiel-Equihua

2009-12-01

Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial

Factors Associated with Vitamin D Testing, Deficiency, Intake, and Supplementation in Patients with Chronic Pain.

Science.gov (United States)

Gaikwad, Manasi; Vanlint, Simon; Moseley, G Lorimer; Mittinty, Murthy N; Stocks, Nigel

2017-11-02

Vitamin D deficiency is a public health issue, with reports of six- to twenty-five-fold rise in vitamin D testing. Vitamin D deficiency has been linked to many chronic diseases such as diabetes mellitus, cardiovascular disease, depression, and chronic pain. Identifying factors associated with risk of deficiency in individuals with chronic pain will help minimize time and cost. This study aims to examine the factors associated with vitamin D testing, intake, and physician-advised supplementation in individuals with chronic pain. Using a cross-sectional design, data were collected from 465 individuals with chronic pain. These data were analyzed using penalized logistic regression with the LASSO technique. Fifty-seven percent reported being tested for vitamin D, about 40% reported being diagnosed with vitamin D deficiency, and of those who had been tested, 60% reported taking vitamin D supplementation. The findings suggest older age (OR 3.12, CI [1.02, 9.50]) and higher mean pain intensity score (OR 2.02, CI [1.13, 3.59]) increased an individual's chance of being vitamin D deficient. Unemployment or on leave due to pain (OR 1.79, [CI 1.03, 3.11]), part-time employment (OR 1.86, CI [1.02, 3.39]), and being a resident of Australia (OR 2.32, CI [1.13, 4.72]) increased chances of being tested for vitamin D. Being diagnosed with vitamin D deficiency (OR 6.67, CI [2.75, 16.19]), unemployed or on leave due to pain (OR 3.71, CI [1.25, 11.00]), and in part-time employment (OR 2.69, CI [0.86, 8.38]) were associated with physician-advised vitamin D supplementation. Our results may have practical implications, as identifying pretest risk factors may assist in identifying who is at risk of vitamin D deficiency, whom to test, and when to treat.

[Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

Science.gov (United States)

Mañú Pereira, María Del Mar; Cabot, Anna; Martínez González, Ana; Sitjà Navarro, Eulalia; Cararach, Vicent; Sabrià, Josep; Boixaderas, Jordi; Teixidor, Roser; Bosch, Albert; López Vílchez, M Angeles; Martín Ibáñez, Itziar; Carrión, Teresa; Plaja, Pere; Sánchez, Mario; Vives Corrons, José Luis

2007-06-30

The prevalence of hemoglobinopathies and glucose-6-phosphate dehidrogenase (G6PD) deficiency in the Catalan neonatal population is increasing due to immigration. Coinheritance of more than a single RBC genetic defect is becoming more frequent and diagnostic pitfalls are also increasing. We intended to demonstrate the need to perform an early diagnosis of sickle cell disease (SCD) by means of neonatal screening, to establish the prevalence of SCD associated with alpha thalassemia and G6PD deficiency and to identify genotypes associated with sickle cell disease and G6PD deficiency. 4,020 blood samples from newborns were screened. For the screening of hemoglobinopathies the high performance liquid chromatography method was used and for G6PD deficiency the fluorescent spot test was employed. We studied the association between betaS gene and alpha thalassaemia del-3.7 Kb. SCD and G6PD deficiency genotypes were established. Prevalence of SCD in population at risk was 1/475 newborns. Prevalence of G6PD deficiency in population at risk was 1/43, and in autochthonous population was 1/527 newborns. In all the cases, sickle hemoglobin was confirmed by ARMS (amplification refractory mutation system). Association between betaS gene and alpha thalassaemia del-3.7 Kb was found in 32.2% of the samples, and an association between betaS gene and G6PD deficiency was observed in 7% of the samples. This study confirms the high prevalence of SCD and G6PD deficiency in population at risk as well as their genetic and clinical heterogeneity. The study of genotype/phenotype relationships allows a better knowledge of molecular mechanism and is useful to establish suitable criteria of diagnosis.

Iron-Deficiency Anemia

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Full Text Available ... Are you curious about how inflammation from chronic diseases can cause iron-deficiency anemia? Read more When there is ... DBDR) is a leader in research on the causes, prevention, and treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research ...

Iron deficiency anemia

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Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

Nanographenes as electron-deficient cores of donor-acceptor systems.

Science.gov (United States)

Liu, Yu-Min; Hou, Hao; Zhou, Yan-Zhen; Zhao, Xin-Jing; Tang, Chun; Tan, Yuan-Zhi; Müllen, Klaus

2018-05-15

Conjugation of nanographenes (NGs) with electro-active molecules can establish donor-acceptor π-systems in which the former generally serve as the electron-donating moieties due to their electronic-rich nature. In contrast, here we report a series of reversed donor-acceptor structures are obtained by C-N coupling of electron-deficient perchlorinated NGs with electron-rich anilines. Selective amination at the vertexes of the NGs is unambiguously shown through X-ray crystallography. By varying the donating ability of the anilino groups, the optical and assembly properties of donor-acceptor NGs can be finely modulated. The electron-deficient concave core of the resulting conjugates can host electron-rich guest molecules by intermolecular donor-acceptor interactions and gives rise to charge-transfer supramolecular architectures.

Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

DEFF Research Database (Denmark)

Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E

2007-01-01

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... incision repair (P = 0.014) were all increased, while protein oxidation decreased (P = 0.003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may...

Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.

Directory of Open Access Journals (Sweden)

Hao Wang

Full Text Available Hepatoma-derived growth factor (HDGF related protein 2 (HRP2 and lens epithelium-derived growth factor (LEDGF/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E 13.5. Histological examination revealed ventricular septal defect (VSD associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s, RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality

ECONOMICAL BASIS TO ADDRESS MICRONUTRIENT DEFICIENCIES IN DEVELOPING WORLD

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Amirul Hassan

2015-12-01

Full Text Available Malnutrition has been called by economists at the World Bank as the “non-human face” of poverty,1 Adults who were malnourished as children earn at least 20% less on average than those who weren’t , 2.Malnutrition is often caused by underlying economics, i.e. the lack of money. Economics is very important in regards to malnutrition; it allows an individual to purchase nutrients. In many places around the world, a lack of money prevents the purchase of a variety of foods. The lack in variety usually leads to micronutrient malnutrition. Economics also decides the production of food in all countries around the world and the ability of a country to overcome difficult times. Thus economics affects ALL people at ALL levels of society, 3.Micronutrient deficiencies also known as ‘hidden hunger’ are determining and aggravating factors for health status and quality of life. It is estimated half of anaemia cases are due to iron deficiency , 4.  Almost half of children in low- and middle-income countries – 47% of under-fives are affected by anaemia, impairing cognitive and physical development,5. Iodine deficiency is the greatest single cause of mental retardation and brain damage. Coincidently,  the number of countries in which iodine-deficiency disorders were considered a public health concern reduced by 43% between 1993 and 2007,6.  Zinc deficiency affects children’s health and physical growth; it is also essential for mothers during pregnancy. It is estimated to cause 4% of deaths in pre-school aged children in lower-income countries. 7 . The Global Burden of Disease estimates showed that among the 26 major risk factors of the global burden of disease,8 iron deficiency ranks ninth overall, zinc deficiency is eleventh, and vitamin A deficiency, is thirteenth. Annually each developing country of the world are losing over millions or billions US $ in Gross Domestic Product (GDP to vitamins and minerals deficiencies. But scaling up

Nutritional iron deficiency in women of child bearing age - what to do

International Nuclear Information System (INIS)

Ansari, T.; Ali, L.; Aziz, T.; Ara, J.; Liaquat, N.; Tahir, H.

2009-01-01

Background: Iron deficiency is the most common aetiology of anaemia worldwide and has several risk factors. Although iron deficiency anaemia (IDA) can occur at any age, women from reproductive age group are particularly vulnerable to develop IDA due to increased nutritional demand during pregnancy. Objective was to determine the frequency and nutritional risk factor of iron deficiency anaemia in women of child bearing age. This descriptive, cross sectional study was conducted from October 2005 to March 2006 at the Department of Medicine, Ward-5, and out-patients department of Jinnah Postgraduate Medical Centre, Karachi. Method: Two hundred non-pregnant females of child bearing age were included in the study; 100 with no previous pregnancy and remaining 100 with at least one prior history of pregnancy. All the relevant information, i.e., demographic and socioeconomic was collected through a questionnaire. Results: Two hundred patients with signs and symptoms of anaemia were recruited. Out of them 89 patients were found to be having iron deficiency anaemia in various age groups. Results also showed that dietary habit of patients was one of the causative factors leading to iron deficiency anaemia. Conclusion: To overcome iron deficiency anaemia a thorough and comprehensive strategy is required, i.e., educating the subjects to consume food rich in iron, community based program, monitoring severely anaemic cases and their treatment. (author)

Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis.

Science.gov (United States)

Maiorana, Arianna; Vergine, Gianluca; Coletti, Valentina; Luciani, Matteo; Rizzo, Cristiano; Emma, Francesco; Dionisi-Vici, Carlo

2014-01-01

Refeeding syndrome can occur in several contexts of relative malnutrition in which an overaggressive nutritional support is started. The consequences are life threatening with multiorgan impairment, and severe electrolyte imbalances. During refeeding, glucose-involved insulin secretion causes abrupt reverse of lipolysis and a switch from catabolism to anabolism. This creates a sudden cellular demand for electrolytes (phosphate, potassium, and magnesium) necessary for synthesis of adenosine triphosphate, glucose transport, and other synthesis reactions, resulting in decreased serum levels. Laboratory findings and multiorgan impairment similar to refeeding syndrome also are observed in acute thiamine deficiency. The aim of this study was to determine whether thiamine deficiency was responsible for the electrolyte imbalance caused by tubular electrolyte losses. We describe two patients with leukemia who developed acute thiamine deficiency with an electrolyte pattern suggestive of refeeding syndrome, severe lactic acidosis, and evidence of proximal renal tubular dysfunction. A single thiamine administration led to rapid resolution of the tubular dysfunction and normalization of acidosis and electrolyte imbalance. This demonstrated that thiamine deficiency was responsible for the electrolyte imbalance, caused by tubular electrolyte losses. Our study indicates that, despite sharing many laboratory similarities, refeeding syndrome and acute thiamine deficiency should be viewed as separate entities in which the electrolyte abnormalities reported in cases of refeeding syndrome with thiamine deficiency and refractory lactic acidosis may be due to renal tubular losses instead of a shifting from extracellular to intracellular compartments. In oncologic and malnourished patients, individuals at particular risk for developing refeeding syndrome, in the presence of these biochemical abnormalities, acute thiamine deficiency should be suspected and treated because it promptly

Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report.

Science.gov (United States)

Alameri, Majid; Shakra, Mustafa; Alsaadi, Taoufik

2015-11-23

Unexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood. We report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

Peripheral neuropathy in a copper-deficient goat

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Valdir Morais de Almeida

2017-09-01

Full Text Available ABSTRACT: This report aimed to describe a case of peripheral neuropathy in a copper-deficient goat, and highlights the clinical, and pathological features of the disease. The goat had low body score, hyporexia, alopecia, achromotrichia, left hindlimb protraction, paralysis with dragging of digit and difficulty to stand up and microcytic normochromic anemia. Copper concentration in serum was markedly lower (2.0µmol L-1 whereas the iron serum content was significantly increased (51.0µmol L-1. The main gross alteration was the reduction of the quadriceps vastus laterallis muscle volume. Histologically, there was atrophy of the quadriceps vastus laterallis muscle and presence of satellite cells, infiltration of lymphocytes, macrophages and replacement of the fibers by connective tissue. In the femoral nerve, there was axonal degeneration with myelin sheath expansion and presence of vacuoles, usually in chains and containing axonal debris or macrophages. Clinical, laboratorial and pathologic findings are consistent with peripheral neuropathy due to a severy copper deficiency.

Serendipitous Discovery of Factor VII Deficiency and the Ensuing Dilemma.

Science.gov (United States)

Umakanthan, Jayadev M; Dhakal, Prajwal; Gundabolu, Krishna; Koepsell, Scott A; Baljevic, Muhamed

2018-03-01

Congenital factor VII deficiency is a challenging disorder to manage, as it is associated with varied genotypes that do not clinically correlate with a bleeding phenotype. Individuals with severe factor VII deficiency (FVII: c 5%) may experience severe hemorrhages. In modern medicine, due to extensive routine pre-operative laboratory testing, clinically asymptomatic patients without any bleeding history might be incidentally discovered, raising clinical dilemmas. Careful consideration of bleeding versus thrombosis risk has to be made in such cases, especially in the elderly. Clinical history of no prior bleeding complications may be a reassuring factor. Minimal required replacement dosing of recombinant activated factor VII can be given peri-operatively in such situations, with close monitoring.

Measurement of antiacetylcholine receptor auto-antibodies in ...

African Journals Online (AJOL)

Two different acetylcholine receptor (AChR) preparations derived from amputated human muscle (AChRAMP) and from the human rhabdomyosarcoma cell line TE671 (AChRTE67,) were compared in radio-immunoprecipitation assays for the detection of AChR auto-antibodies in serum specimens from 20 patients with ...

An Assessment of the Selenium Status of Iodine-Deficient and Non-Iodine Deficient Filipino Children

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Ma. Sofia Amarra

2002-06-01

Full Text Available The aim of this study is to examine and compare blood selenium levels in iodine-deficient and non-iodine deficient children. Two groups of children were examined: one group with iodine deficiency (n=31 and the other group with normal iodine status (n=32. Blood was extracted by venipuncture from children aged 6-10 years attending first grade in Commonwealth Elementary School in Quezon City. Whole blood selenium was examined by electrothermal atomic absorption spectrophotometry (AAS. Iodine status was determined by goiter palpation and urinary iodine excretion. Mean selenium levels of deficient and non-deficient children were compared using T-test. Using a cut-off value of 60 mg Se/L whole blood, the proportion of children with normal and deficient iodine status who fell below this cut-off was compared using chi-square test. Whole blood selenium values ranged from 17.6 to 133.6 mg/L. There were no significant differences in mean selenium levels between children with normal and deficient iodine status. Children with normal iodine status had a mean blood selenium level of 55.87 ± 26.3 mg/L while children with deficient iodine status had a mean level of 58.76 ± 26.4 mg/L. Sixty percent of children had blood selenium levels below the arbitrary cut-off of 60 mg/L with no significant difference between groups (p = 0.165, indicating that selenium deficiency is prevalent in this group of children regardless of iodine status. Since selenium deficiency limits the response to iodine supplementation, further investigation is needed to determine whether the same situation exists in children from other areas.

Dietary zinc deficiency effects dorso-lateral and ventral prostate of Wistar rats: histological, biochemical and trace element study.

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Joshi, Sangeeta; Nair, Neena; Bedwal, R S

2014-10-01

Zinc deficiency has become a global problem affecting the developed and developing countries due to inhibitors in the diet which prevents its absorption or due to a very low concentration of bioavailable zinc in the diet. Being present in high concentration in the prostate and having diverse biological function, we investigated the effects of dietary zinc deficiency for 2 and 4 weeks on dorso-lateral and ventral prostate. Sixty prepubertal rats were divided into three groups: zinc control (ZC), pair fed (PF) and zinc deficient (ZD) and fed on 100 μg/g (zinc control and pair fed groups) and 1 μg/g (zinc deficient) diet. Zinc deficiency was associated with degenerative changes in dorso-lateral and ventral prostate as made evident by karyolysis, karyorhexis, cytoplasmolysis, loss of cellularisation, decreased intraluminar secretion and degeneration of fibromuscular stroma. In response, protein carbonyl, nitric oxide, acid phosphatase, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase increased, exhibiting variable level of significance. Total protein and total zinc concentration in dorso-lateral and ventral prostate as well as in serum decreased (P dorso-lateral and ventral prostate after dietary zinc deficiency as well as impairment of metabolic and secretory activity, reduced gonadotropin levels by hypothalamus -hypophysial system which is indicative of a critical role of zinc in maintaining the prostate integrity.

[Iron deficiency and pica].

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Muñoz, J A; Marcos, J; Risueño, C E; de Cos, C; López, R; Capote, F J; Martín, M V; Gil, J L

1998-02-01

To study the relationship between pica and iron-lack anaemia in a series of iron-deficiency patients in order to establish the pathogenesis of such relationship. Four-hundred and thirty-three patients were analysed. Pica was studied by introducing certain diet queries into the clinical history. All patients received oral iron and were periodically controlled with the usual clinico-haematological procedures. Pica was present in 23 patients (5.3%). Eight nourishing (namely, coffee grains, almonds, chocolate, ice, lettuce, carrots, sunflower seeds and bread) and 2 non-nourishing (clay and paper) substances were involved. A second episode of pica appeared in 9 cases upon relapsing of iron deficiency. Both anaemia and pica were cured by etiologic and substitutive therapy in all instances. No clear correlation was found with either socio-economic status or pathogenetic causes of iron deficiency and pica, and no haematological differences were seen between patients with pica and those without this alteration. (1) The pathogenesis of pica is unclear, although it appears unrelated to the degree of iron deficiency. (2) According to the findings in this series, pica seems a consequence of iron deficiency rather than its cause. (3) Adequate therapy can cure both conditions, although pica may reappear upon relapse of iron deficiency.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Topics section only, or the News and Resources section. NHLBI Entire Site NHLBI Entire Site Health ... español Iron-deficiency anemia is a common type of anemia that occurs if you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount of iron. Read less Participate in NHLBI Clinical Trials We lead or sponsor many studies related to iron-deficiency anemia. See if you ...

Advisory Committee on human radiation experiments. Final report, Supplemental Volume 2. Sources and documentation

International Nuclear Information System (INIS)

1995-01-01

This volume and its appendixes supplement the Advisory Committee's final report by reporting how we went about looking for information concerning human radiation experiments and intentional releases, a description of what we found and where we found it, and a finding aid for the information that we collected. This volume begins with an overview of federal records, including general descriptions of the types of records that have been useful and how the federal government handles these records. This is followed by an agency-by-agency account of the discovery process and descriptions of the records reviewed, together with instructions on how to obtain further information from those agencies. There is also a description of other sources of information that have been important, including institutional records, print resources, and nonprint media and interviews. The third part contains brief accounts of ACHRE's two major contemporary survey projects (these are described in greater detail in the final report and another supplemental volume) and other research activities. The final section describes how the ACHRE information-nation collections were managed and the records that ACHRE created in the course of its work; this constitutes a general finding aid for the materials deposited with the National Archives. The appendices provide brief references to federal records reviewed, descriptions of the accessions that comprise the ACHRE Research Document Collection, and descriptions of the documents selected for individual treatment. Also included are an account of the documentation available for ACHRE meetings, brief abstracts of the almost 4,000 experiments individually described by ACHRE staff, a full bibliography of secondary sources used, and other information

AChR-specific immunosuppressive therapy of myasthenia gravis.

Science.gov (United States)

Luo, Jie; Lindstrom, Jon

2015-10-15

Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. Copyright © 2015 Elsevier Inc. All rights reserved.

Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose.

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Phillpotts, Simon; Tash, Elliot; Sen, Sambit

2014-11-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Iron deficiency or anemia of inflammation? : Differential diagnosis and mechanisms of anemia of inflammation.

Science.gov (United States)

Nairz, Manfred; Theurl, Igor; Wolf, Dominik; Weiss, Günter

2016-10-01

Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body's iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear phagocytes system in liver and spleen. This results in iron-limited erythropoiesis and anemia. This review summarizes current diagnostic and pathophysiological concepts of iron deficiency anemia and anemia of inflammation, as well as combined conditions, and provides a brief outlook on novel therapeutic options.

Additional costs to Finnish dairy farms due to occupational safety and health

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Tapio Klen

1988-03-01

Full Text Available The additional costs incurred by work safety measures to dairy farms were estimated by interviewing 95 dairy farmers and inspecting with them production buildings, machines and the need for personal protective devices at a commune. The present value of the implemented safety and health improvements rose to FIM 22 000 per farm in 1983. About FIM 17000 were due to the tractors, FIM 3 000 to the cow houses and FIM 2 000 to other machines and tools than tractors. The protective equipment of tractors caused the annual maintenance cost of FIM 4 350 and cow house FIM 650, if the interest rate were 10 %. The annual total cost was over FIM 6 000. The replacement value would have been about FIM 31 000 in 1983. If all deficiences still remaining in 1983 had been corrected at once, the total cost would have been about FIM 12000 per farm, which leads to an annual cost of FIM 3 100. As for still remaining deficiencies, the study suggested need for an annual cost of about FIM 1 500 due to personal protectors. Half of this sum was due to need for the acquisition of personal safety equipment for forest work. Correcting the safety and health deficiencies of the cowshed and agricultural machines would produce each an annual cost of about FIM 800 per farm. The present value of the labor protection investments in 1983 was FIM 22 000 per farm, and there still remained need to invest an additional FIM 12000 in order to eliminate the remaining deficiencies. So, the theoretical total of the annual maintenance cost would have been FIM 6 600—9 200 per farm depending on the interest rate. Because the study concerned only one commune, the results cannot be generalized to the whole country.

Ophthalmic manifestations of vitamin A and D deficiency in two autistic teenagers: case reports and a review of the literature.

LENUS (Irish Health Repository)

Duignan, Emma

2015-01-01

We describe the cases of 2 autistic children with ophthalmic and systemic manifestations of vitamin A deficiency due to food faddism. Although vitamin A deficiency is common in the developing world, reports in developed societies are rare. Our patients presented over a 1-year period. The patients were 14 and 13 years old at the time of presentation and were both found to have marked features of vitamin A deficiency related to unusual dietary habits. Anterior segment signs of xerophthalmia were present in both patients. In addition, patient 1 showed evidence of a rod-predominant retinopathy, which resolved with vitamin A supplementation. Due to its rare occurrence, hypovitaminosis A must be highlighted and anticipated in this cohort.

Diagnóstico diferencial da deficiência de ferro Differential diagnosis of iron deficiency

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Perla Vicari

2010-06-01

Full Text Available A deficiência de ferro é considerada a patologia hematológica mais prevalente no homem. Assim, é fundamental a adequada identificação de suas causas, bem como a diferenciação com outras patologias distintas para adequada abordagem da deficiência de ferro. Neste artigo são brevemente descritas outras condições que podem cursar com anemia microcítica, tais como: talassemias, anemia de doença crônica, anemia sideroblástica e envenenamento por chumbo, patologias estas que devem ser afastadas durante investigação de anemia ferropriva.Iron deficiency is considered to be the commonest hematological pathology in humans. Thus, the essential steps in an adequate approach of iron deficiency include: the proper identification of its causes and the differentiation between iron deficiency and other conditions. This article briefly describes other conditions that may present with microcytic anemia such as thalassemia, anemia of chronic diseases, sideroblastic anemia and lead intoxication. These diseases should be considered during the investigation of iron deficiency anemia.

White centered retinal hemorrhages in vitamin b(12) deficiency anemia.

Science.gov (United States)

Zehetner, Claus; Bechrakis, Nikolaos E

2011-05-01

To report a case of severe vitamin B(12) deficiency anemia presenting with white centered retinal hemorrhages. Interventional case report. A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B(12) deficiency requiring erythrocyte transfusions. Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B(12) deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

White Centered Retinal Hemorrhages in Vitamin B12 Deficiency Anemia

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Claus Zehetner

2011-05-01

Full Text Available Background: To report a case of severe vitamin B12 deficiency anemia presenting with white centered retinal hemorrhages. Methods: Interventional case report. Results: A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B12 deficiency requiring erythrocyte transfusions. Discussion: Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B12 deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis.

Science.gov (United States)

Peeler, Crandall E; De Lott, Lindsey B; Nagia, Lina; Lemos, Joao; Eggenberger, Eric R; Cornblath, Wayne T

2015-10-01

The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the

MHC class II deficiency: Report of a novel mutation and special review.

Science.gov (United States)

Farrokhi, S; Shabani, M; Aryan, Z; Zoghi, S; Krolo, A; Boztug, K; Rezaei, N

The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Iron deficiency anemia and Plummer–Vinson syndrome: current insights

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Goel A

2017-10-01

Full Text Available Amit Goel,1 Satvinder Singh Bakshi,2 Neetu Soni,3 Nanda Chhavi4 1Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 2Department of Otorhinolaryngology and Head and Neck Surgery, Mahatma Gandhi Medical College and Research Institute, Puducherry, India; 3Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 4Department of Pediatrics, Era’s Lucknow Medical College, Lucknow, India Abstract: Plummer–Vinson syndrome (PVS, a rare clinical condition, is characterized by a triad of dysphagia, iron deficiency anemia and esophageal web in the post-cricoid region. It was first described over a century ago. However, literature on this condition remains scanty, and its prevalence appears to be declining worldwide, possibly due to improvements in nutrition over time. The condition has been reported most commonly in thin-built, middle-aged, white women. The esophageal webs in PVS are thin mucosal folds, which are best seen either in lateral views at barium swallow or at esophagoscopy. These are usually semilunar or crescentic, being located most often along the anterior esophageal wall, but can be concentric. The exact cause and pathogenesis of PVS remain unclear, though iron and other nutritional deficiencies, genetic predisposition and autoimmunity have all been implicated in formation of the webs. Treatment includes correction of iron deficiency and endoscopic dilation of the esophageal webs to relieve dysphagia. PVS is associated with an increased risk of hypopharyngeal and esophageal malignancies. Correction of iron deficiency may arrest and reverse the mucosal changes and possibly reduces this risk. Keywords: Plummer–Vinson syndrome, Paterson–Brown–Kelly syndrome, esophageal web, dysphagia, iron deficiency anemia

Manganese deficiency in plants

DEFF Research Database (Denmark)

Schmidt, Sidsel Birkelund; Jensen, Poul Erik; Husted, Søren

2016-01-01

Manganese (Mn) is an essential plant micronutrient with an indispensable function as a catalyst in the oxygen-evolving complex (OEC) of photosystem II (PSII). Even so, Mn deficiency frequently occurs without visual leaf symptoms, thereby masking the distribution and dimension of the problem...... restricting crop productivity in many places of the world. Hence, timely alleviation of latent Mn deficiency is a challenge in promoting plant growth and quality. We describe here the key mechanisms of Mn deficiency in plants by focusing on the impact of Mn on PSII stability and functionality. We also address...... the mechanisms underlying the differential tolerance towards Mn deficiency observed among plant genotypes, which enable Mn-efficient plants to grow on marginal land with poor Mn availability....

Importance of pharmacokinetic studies in the management of acquired factor X deficiency.

Science.gov (United States)

Lim, Ming Y; McCarthy, Timothy; Chen, Sheh-Li; Rollins-Raval, Marian A; Ma, Alice D

2016-01-01

Up to 14% of individuals with systemic AL amyloidosis develop acquired factor X deficiency, which occurs due to adsorption of factor X onto amyloid fibrils. Although baseline factor X levels are not predictive of bleeding risk in these patients, serious hemorrhagic complications can occur, particularly during invasive procedures. Optimal management strategies to attenuate bleeding risk in these patients are unknown. We describe our experience in the management of acquired factor X deficiency, secondary to systemic AL amyloidosis, in a case series of three patients who received prothrombin complex concentrates (PCCs) for treatment and prevention of bleeding events. We performed a retrospective review extracting information on baseline demographics, laboratory data, pharmacokinetic (PK) studies, and clinically documented bleeding events. Our case series demonstrates that individuals with acquired factor X deficiency secondary to amyloidosis have variable laboratory and clinical responses to PCCs. This is likely due to distinct amyloid loads and fibril sequences, leading to different binding avidities for factor X. Our data emphasize the importance of performing PK testing prior to any invasive procedures to determine the dose and frequency interval to achieve adequate factor X levels for hemostasis, given the variable response between individuals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Urinary reducing substances in neonatal intrahepatic cholestasis caused by citrin deficiency

Directory of Open Access Journals (Sweden)

Ajmal Kader

2014-06-01

Full Text Available Neonatal cholestasis due to citrin deficiency is an autosomal recessive metabolic disorder caused by mutations in SLC25A13 gene. Mutations in this gene have a relatively high prevalence in East-Asian races compared to European or Afro-Caribbean races. Mutations in both sets of chromosomes often lead to self-limiting early onset cholestasis and growth retardation referred as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD. It is associated with a wide range of metabolic derangements including galactosemia and aminoacidemia, which can be detected on the newborn blood spot screening. Galactose, being a reducing sugar, can also be detected using Clinitest® (Clinitest® Reagent Tablets, Bayer Corporation, Diagnostics Division, Elkhart, IN, USA, a common screening test used in the work up of metabolic and hepatic diseases. In the western population classical galactosemia is often suspected when non glucose reducing substances are detected in the urine of infants with cholestasis. However in East-Asian races the prevalence of classical galactosemia is very low whilst galactosemia due to altered uridine diphosphate-galactose epimerase activity in NICCD is more common. We present a case of NICCD in an East-Asian infant with cholestasis and persistently positive urine reducing substance. Conclusion: NICCD deficiency should be considered as a differential diagnosis in any infant with cholestasis and persistently positive urinary reducing substances.

Progressive pituitary hormone deficiency following radiation therapy in adults

International Nuclear Information System (INIS)

Loureiro, Rafaela A.; Vaisman, Mario

2004-01-01

Hypopituitarism can be caused by radiation therapy, even when it is not directly applied on the hypothalamic-pituitary axis, and can lead to anterior pituitary deficiency mainly due to hypothalamic damage. The progressive loss of the anterior pituitary hormones usually occurs in the following order: growth hormone, gonadotropin hormones, adrenocorticotropic hormone and thyroid-stimulating hormone. Although there are several different tests available to confirm anterior pituitary deficiency, this paper will focus on the gold standard tests for patients submitted to radiation therapy. We emphasize that the decline of anterior pituitary function is time- and dose-dependent with some variability among the different axes. Therefore, awareness of the need of a joint management by endocrinologists and oncologists is essential to improve treatment and quality of life of the patients. (author)

26 CFR 156.6161-1 - Extension of time for paying tax or deficiency.

Science.gov (United States)

2010-04-01

... shown on the notice and demand. In exceptional cases, a further extension for a period not in excess of... deficiency is due to negligence, to intentional disregard of rules and regulations, or to fraud with intent...

Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency.

Directory of Open Access Journals (Sweden)

Jonghan Kim

Full Text Available Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI. Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT and dopamine receptor D(1 (D1R levels were reduced and dopamine receptor D(2 (D2R levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.

Posterior fossa syndrome in a patient with an ornithine transcarbamylase deficiency

NARCIS (Netherlands)

Nedermeijer, S. C M; Van Den Hout, J.; Geleijns, C.; De Klerk, H.; Catsman-Berrevoets, C. E.

2015-01-01

The posterior fossa syndrome (PFS) is a well-known clinical entity and mainly occurs in children. Ornithine transcarbamylase deficiency (OTC) is the most common urea cycle disorder, which occurs in an estimated 1 per 50.000 live births in Japan. Symptoms are mostly due to hyperammonemia and include

Action of nereistoxin on recombinant neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes.

Science.gov (United States)

Raymond Delpech, Valérie; Ihara, Makoto; Coddou, Claudio; Matsuda, Kazuhiko; Sattelle, David B

2003-11-01

Nereistoxin (NTX), a natural neurotoxin from the salivary glands of the marine annelid worm Lumbriconereis heteropoda, is highly toxic to insects. Its synthetic analogue, Cartap, was the first commercial insecticide based on a natural product. We have used voltage-clamp electrophysiology to compare the actions of NTX on recombinant nicotinic acetylcholine receptors (nicotinic AChRs) expressed in Xenopus laevis oocytes following nuclear injection of cDNAs. The recombinant nicotinic AChRs investigated were chicken alpha7, chicken alpha4beta2 and the Drosophila melanogaster/chicken hybrid receptors SAD/beta2 and ALS/beta2. No agonist action of NTX (0.1-100 microM) was observed on chicken alpha7, chicken alpha4beta2 and the Drosophila/chicken hybrid nicotinic AChRs. Currents elicited by ACh were reduced in amplitude by NTX in a dose-dependent manner. The toxin was slightly more potent on recombinant Drosophila/vertebrate hybrid receptors than on vertebrate homomeric (alpha7) or heteromeric (alpha4beta2) nicotinic AChRs. Block by NTX of the chicken alpha7, chicken alpha4beta2 and the SAD/beta2 and ALS/beta2 Drosophila/chicken hybrid receptors is in all cases non-competitive. Thus, the site of action on nicotinic AChRs of NTX, to which the insecticide Cartap is metabolised in insects, differs from that of the major nicotinic AChR-active insecticide, imidacloprid.

Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency

DEFF Research Database (Denmark)

Jackson, Robert S; Creemers, John W M; Farooqi, I Sadaf

2003-01-01

. The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A's negligible PC1 activity......We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound...

Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes.

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Megumi Bessho

Full Text Available Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD, i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

Safeguards and security deficiencies fulfilled through technology development

International Nuclear Information System (INIS)

Smoot, W.

1996-01-01

The Office of Safeguards and Security (OSS) sponsors research and development activities based on identified field and headquarters customer requirements. Annually, a formal solicitation of safeguards and security user needs is conducted. Currently, there are over 300 valid safeguards and security deficiencies that have been identified. These user needs serve as the basis for formulating the OSS Technology Development Program (TDP). Due to budget constraints, the TDP can only address approximately 47% of these needs in FY 1996. This paper will discuss, in a general sense, the current deficiencies and how the TDP is responding to each. Specifically, the paper will highlight technologies in the areas of Material Control and Accounting, Physical Security, and Information Security. A brief discussion of unfulfilled user requirements will also be presented as a catalyst for leveraging available or developing technologies from other similar programs or from private industry

An Unusual Case of Hypercalcemia Associated with Graves’ Disease and Vitamin D Deficiency

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Evgenia Korytnaya

2011-01-01

Full Text Available Objective To present a case of hypercalcemia associated with thyrotoxicosis in a patient with vitamin D deficiency and review biochemical changes during the course of treatment. Methods We report a case, describe the changes in serum calcium, phosphorus, parathyroid hormone in Graves’ disease and concomitant Vitamin D deficiency. We compare our findings to those reported in literature. Results Our patient had hypercalcemia secondary to thyrotoxicosis alone, which was confirmed by low parathyroid hormone level and resolution of hypercalcemia with treatment of thyrotoxicosis. The case was complicated by a concomitant vitamin D deficiency. Serum calcium elevation in patients with thyrotoxicosis occurs secondary to hyperthyroidism alone or due to concurrent hyperparathyroidism. Hypercalcemia from thyrotoxicosis is usually asymptomatic and is related to bone resorption. Vitamin D deficiency can be seen in patients with thyrotoxicosis because of accelerated metabolism, poor intestinal absorption and increased demand during bone restoration phase. Coexistence of hypercalcemia and Vitamin D deficiency in patients with thyrotoxicosis is rare, but possible, and 25-hydroxyvitamin D levels should be checked. The definite treatment for hypercalcemia in thyrotoxicosis is correction of thyroid function. Conclusion Hypercalcemia in thyrotoxicosis should be distinguished from concomitant hyperparathyroidism and confirmed by resolution of hypercalcemia with control of thyrotoxicosis. Patients with hypercalcemia and thyrotoxicosis may also have vitamin D deficiency and 25-OH Vitamin D levels should be checked.

Red-Green Colour Deficiencies and the Study of Science, Computer ...

African Journals Online (AJOL)

Colour blindness is the inability to perceive differences between some or all colours that other people can distinguish. It is most often of genetic nature but may also occur because of eye, nerve or brain damage or due to exposure to some chemicals. The most common type of colour vision deficiency is red-green colour ...

Measurement of anti- acetylcholine receptor auto-antibodies in ...

African Journals Online (AJOL)

auto-antibodies in myasthenia gravis. K. J. Steenkamp, W. Duim, M. s. Myer,. S. C. K. Malfeld, R. Anderson. Two different acetylcholine receptor (AChR) preparations derived from ... the detection of AChR auto-antibodies in serum specimens from 20 ... 4°C. Thereafter, 1 ml of washing solution (phosphate- buffered saline ...

Sudden unexpected infant death (SUDI in a newborn due to medium chain acyl CoA dehydrogenase (MCAD deficiency with an unusual severe genotype

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Lovera Cristina

2012-10-01

Full Text Available Abstract Medium chain acyl CoA dehydrogenase deficiency (MCAD is the most common inborn error of fatty acid oxidation. This condition may lead to cellular energy shortage and cause severe clinical events such as hypoketotic hypoglycemia, Reye syndrome and sudden death. MCAD deficiency usually presents around three to six months of life, following catabolic stress as intercurrent infections or prolonged fasting, whilst neonatal-onset of the disease is quite rare. We report the case of an apparently healthy newborn who suddenly died at the third day of life, in which the diagnosis of MCAD deficiency was possible through peri-mortem blood-spot acylcarnitine analysis that showed very high concentrations of octanoylcarnitine. Genetic analysis at the ACADM locus confirmed the biochemical findings by demonstrating the presence in homozygosity of the frame-shift c.244dup1 (p.Trp82LeufsX23 mutation, a severe genotype that may explain the unusual and very early fatal outcome in this newborn. This report confirms that inborn errors of fatty acid oxidation represent one of the genetic causes of sudden unexpected deaths in infancy (SUDI and underlines the importance to include systematically specific metabolic screening in any neonatal unexpected death.

Zinc deficiency in field-grown pecan trees: changes in leaf nutrient concentrations and structure.

Science.gov (United States)

Ojeda-Barrios, Dámaris; Abadía, Javier; Lombardini, Leonardo; Abadía, Anunciación; Vázquez, Saúl

2012-06-01

Zinc (Zn) deficiency is a typical nutritional disorder in pecan trees [Carya illinoinensis (Wangenh.) C. Koch] grown under field conditions in calcareous soils in North America, including northern Mexico and south-western United States. The aim of this study was to assess the morphological and nutritional changes in pecan leaves affected by Zn deficiency as well as the Zn distribution within leaves. Zinc deficiency led to decreases in leaf chlorophyll concentrations, leaf area and trunk cross-sectional area. Zinc deficiency increased significantly the leaf concentrations of K and Ca, and decreased the leaf concentrations of Zn, Fe, Mn and Cu. All nutrient values found in Zn-deficient leaves were within the sufficiency ranges, with the only exception of Zn, which was approximately 44, 11 and 9 µg g(-1) dry weight in Zn-sufficient, moderately and markedly Zn-deficient leaves, respectively. Zinc deficiency led to decreases in leaf thickness, mainly due to a reduction in the thickness of the palisade parenchyma, as well as to increases in stomatal density and size. The localisation of Zn was determined using the fluorophore Zinpyr-1 and ratio-imaging technique. Zinc was mainly localised in the palisade mesophyll area in Zn-sufficient leaves, whereas no signal could be obtained in Zn-deficient leaves. The effects of Zn deficiency on the leaf characteristics of pecan trees include not only decreases in leaf chlorophyll and Zn concentrations, but also a reduction in the thickness of the palisade parenchyma, an increase in stomatal density and pore size and the practical disappearance of Zn leaf pools. These characteristics must be taken into account to design strategies to correct Zn deficiency in pecan tree in the field. Copyright © 2012 Society of Chemical Industry.

Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

NARCIS (Netherlands)

Mudd, S.H.; Cerone, R.; Schiaffino, M.C.; Fantasia, A.R.; Minniti, G.; Caruso, U.; Lorini, R.; Watkins, D.; Matiaszuk, N.; Rosenblatt, D.S.; Schwahn, B.; Rozen, R.; Gros, L. Le; Kotb, M.; Capdevila, A.; Luka, Z.; Finkelstein, J.; Tangerman, A.; Stabler, S.P.; Allen, R.; Wagner, C.

2001-01-01

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or

Ornithine Transcarbamylase Deficiency: If at First You Do Not Diagnose, Try and Try Again

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Christan D. Santos

2017-01-01

Full Text Available Ornithine transcarbamylase (OTC deficiency is well known for its diagnosis in the neonatal period. Presentation often occurs after protein feeding and manifests as poor oral intake, vomiting, lethargy progressing to seizure, respiratory difficulty, and eventually coma. Presentation at adulthood is rare (and likely underdiagnosed; however, OTC deficiency can be life-threatening and requires prompt investigation and treatment. Reports and guidelines are scarce due to its rarity. Here, we present a 59-year-old woman with a past history of irritable bowel syndrome who underwent a reparative operation for rectal prolapse and enterocele. Her postoperative course was complicated by a bowel perforation (which was repaired, prolonged mechanical ventilation, tracheostomy, critical illness myopathy, protein-caloric malnutrition, and altered mental status. After standard therapy for delirium failed, further investigation showed hyperammonemia and increased urine orotic acid, ultimately leading to the diagnosis of OTC deficiency. This case highlights the importance of considering OTC deficiency in hospitalized adults, especially during the diagnostic evaluation for altered mental status.

Medication adherence to oral iron therapy in patients with iron deficiency anemia.

Science.gov (United States)

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

2016-01-01

This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment.

High Prevalence of Vitamin D Deficiency among Pregnant Saudi Women

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Nora A. Al-Faris

2016-02-01

Full Text Available Vitamin D deficiency has emerged as a public health problem worldwide due to its important role in health and disease. The present work is intended to examine prevalence of vitamin D deficiency among pregnant Saudi women and related risk factors. A cross-sectional study was carried out at King Fahad Medical City in Riyadh, Saudi Arabia. Serum 25-hydroxy vitamin D (25(OHD was measured by enzyme-linked immunosorbent assay in 160 pregnant women during the first trimester of pregnancy. Socio-demographic, lifestyle and maternal characteristics were collected and vitamin D intake was assessed using a 24-h dietary recall. Weight and height were measured using standardized methods. Vitamin D deficiency (25(OHD < 50 nmol/L and insufficiency (25(OHD = 50–74 nmol/L were reported in 50% and 43.8% of the study sample, respectively. Median serum 25(OHD concentration was 49.9 nmol/L. Adequate vitamin D intake (≥600 IU/day was reported among only 8.1% of pregnant women. Age group, educational level, sun exposure frequency and daytime and daily practice of exercise were significantly associated with vitamin D status. Overall, vitamin D deficiency was common among pregnant Saudi women in Riyadh. Steps should be taken to address the current situation, including increased sunlight exposure, consumption of fatty fish, and vitamin D supplements.

High Prevalence of Vitamin D Deficiency among Pregnant Saudi Women.

Science.gov (United States)

Al-Faris, Nora A

2016-02-04

Vitamin D deficiency has emerged as a public health problem worldwide due to its important role in health and disease. The present work is intended to examine prevalence of vitamin D deficiency among pregnant Saudi women and related risk factors. A cross-sectional study was carried out at King Fahad Medical City in Riyadh, Saudi Arabia. Serum 25-hydroxy vitamin D (25(OH)D) was measured by enzyme-linked immunosorbent assay in 160 pregnant women during the first trimester of pregnancy. Socio-demographic, lifestyle and maternal characteristics were collected and vitamin D intake was assessed using a 24-h dietary recall. Weight and height were measured using standardized methods. Vitamin D deficiency (25(OH)D L) and insufficiency (25(OH)D = 50-74 nmol/L) were reported in 50% and 43.8% of the study sample, respectively. Median serum 25(OH)D concentration was 49.9 nmol/L. Adequate vitamin D intake (≥600 IU/day) was reported among only 8.1% of pregnant women. Age group, educational level, sun exposure frequency and daytime and daily practice of exercise were significantly associated with vitamin D status. Overall, vitamin D deficiency was common among pregnant Saudi women in Riyadh. Steps should be taken to address the current situation, including increased sunlight exposure, consumption of fatty fish, and vitamin D supplements.

Leukocyte Adhesion Deficiency: Report of Two Family Related Newborn Infants

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Zohreh Kavehmanesh

2010-07-01

Full Text Available "nLeukocyte adhesion deficiency type 1 (LAD 1 is an autosomal recessive hereditary disorder resulting from deficiency of CD18, characterized by recurrent bacterial infections. We report two consanguineous patients with Leukocyte adhesion deficiency type 1( LAD1. These two infant boy patients were referred to us, within a short period of time, with the complaints of recurrent infections at the age of 38 and 75 days -old, respectively. Parents of two patients were first cousins and their grandmothers also were first cousins. The history of delayed umbilical cord separation was shown in both patients. Patient 1 had history of omphalitis, conjunctivitis, skin lesion of groin area and abscess formation of vaccination site, and had infective wound of eye-lid at the last admission. Patient 2 had history of omphalitis and soft tissue infection of right wrist at the last admission. Laboratory findings showed marked leukocytosis and low CD18 levels (6.6% in Patient 1 and 2.4 % in Patient 2. In Patient 1 recurrent infections were treated with antibiotic regimens and received bone marrow transplantation but Patient 2 died because of septicemia, generalized edema, ascites and progression to acute renal failure at 4 months of age. Due to considerable rate of consanguineous marriages in parents of Leukocyte adhesion deficiency patients, sequence analysis especially for prenatal diagnosis in subsequent pregnancies and genetic counseling is recommended.

Vitamin B12 deficiency

DEFF Research Database (Denmark)

Green, Ralph; Allen, Lindsay H; Bjørke-Monsen, Anne-Lise

2017-01-01

, subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age...... remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes...

Extreme hypertriglyceridemia, pseudohyponatremia, and pseudoacidosis in a neonate with lipoprotein lipase deficiency due to segmental uniparental disomy.

Science.gov (United States)

Ashraf, Ambika P; Hurst, Anna C E; Garg, Abhimanyu

Extreme hypertriglyceridemia is rare in the neonatal period. We report a neonate with lipoprotein lipase (LPL) deficiency who presented with diagnostic and management conundrum. A full-term 36-day-old female was noted to have "Pepto-Bismol like" blood when repeating a newborn screening. The initial plasma triglyceride level was 24,318 mg/dL. The laboratory tests revealed serum bicarbonate level of severe anemia. There were no signs of acute distress. The point of care capillary blood testing, however, demonstrated normal serum pH (7.2), bicarbonate (25.4 mmol/L), and sodium (139 mmol/L). The patient had mild elevation of serum lactic acid and no ketonuria. A diagnosis of type I hyperlipoproteinemia was made. Oral feeding was stopped, and the infant received intravenous fluids for the next 7 days resulting in lowering of serum triglyceride levels to 1016 mg/dL. Oral feeding was initiated with an amino acid-rich formula to which medium chain triglycerides were slowly added, while maintaining the total fat content to A, p.(Gly215Glu) mutation. Subsequent analysis of the parental samples revealed that only the father, but not the mother, was a heterozygous carrier of the same mutation. Analysis of 18 informative microsatellite markers on chromosome 8 revealed paternal segmental uniparental disomy with partial absence of the maternal chromosome 8p, confirmed by single-nucleotide polymorphism microarray. We conclude that besides pseudohyponatremia, extreme hypertriglyceridemia can rarely present as pseudoacidosis and uniparental disomy can be an underlying mechanism for autosomal recessive diseases such as LPL deficiency. Published by Elsevier Inc.

SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

Science.gov (United States)

Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing

2016-01-01

Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Monocular Elevation Deficiency - Double Elevator Palsy

Science.gov (United States)

... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

Genetics Home Reference: tyrosine hydroxylase deficiency

Science.gov (United States)

... Email Facebook Twitter Home Health Conditions TH deficiency Tyrosine hydroxylase deficiency Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description Tyrosine hydroxylase (TH) deficiency is a disorder that primarily ...

Seronegative myasthenia gravis associated with malignant thymoma.

Science.gov (United States)

Richards, Jason; Howard, James F

2017-05-01

Myasthenia gravis (MG) is generally caused by antibodies directed against the neuromuscular junction, including antibodies against the postsynaptic nicotinic acetylcholine receptor (AChR). Pathologic abnormalities of the thymus gland, including thymoma, are associated with MG. We report a 56-year-old woman who presented with double vision. Single fiber EMG confirmed myasthenia gravis. AChR, striational muscle and MuSK antibodies were absent in the serum. Chest CT demonstrated a malignant thymoma. We report the first case of seronegative myasthenia gravis associated with malignant thymoma. The case challenges the conventional wisdom that all patients with thymoma associated MG test positive for antibodies against AChR. Copyright © 2017 Elsevier B.V. All rights reserved.

Mandibular Osteitis Fibrosa Cystica as First Sign of Vitamin D Deficiency

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Nour Mellouli

2018-01-01

Full Text Available Introduction. Brown tumors of hyperparathyroidism are locally destructive bone lesions. They are the late clinical consequence of the disease. They can occur in primary, secondary, and rarely tertiary forms. They affect usually long bones and less frequently those of the maxilla. Case Report. Our 45-year-old female patient presented with a mandibular tumor next to the first right lower molar. At first, we have chosen tooth extraction and tumor excision. When the histological report showed the giant cell tumor we suspected a metabolic bone disorder. Biochemical tests screened hyperparathyroidism and severe vitamin D deficiency, and parathyroid scintiscan revealed parathyroid adenoma. Discussion. The association of hyperparathyroidism and vitamin D deficiency leads to diagnostic uncertainty. First, secondary hyperparathyroidism can be due vitamin D deficiency. Second, data available show that vitamin D deficiency is more prevalent in patients with primary hyperparathyroidism than in general population. Hyperparathyroidism management is based on correct and precise diagnosis. Furthermore, the resolution of brown tumors depends on the cure of hyperparathyroidism. In fact, bone lesions should regress after biological tests’ normalization. Conclusion. Clinicians should be aware of such rare and complicated presentation. They must consider the diagnosis of the brown tumor to avoid extensive surgical excision and teeth extractions.

Fatal ammonia toxicity in an adult due to an undiagnosed urea cycle defect: under-recognition of ornithine transcarbamylase deficiency.

Science.gov (United States)

Thurlow, Vanessa R; Asafu-Adjaye, Michelle; Agalou, Stamatina; Rahman, Yusof

2010-05-01

There is a lack of awareness of acutely presenting inborn errors of metabolism in adults, of which the X-linked urea cycle defect ornithine transcarbamylase (OTC) deficiency is an example, many comparatively mild mutations having been identified. In male hemizygotes clinical manifestations and age at presentation vary and depend on the mutation. In female heterozygotes the clinical spectrum depends on the extent to which the abnormal gene is expressed. Milder versions of the defect may not cause clear clinical symptoms and may remain unrecognized until the person is subjected to an unusually high nitrogen load when they develop severe hyperammonaemia. During acute episodes liver enzymes may be normal or only slightly elevated and occasionally accompanied by coagulopathy, but the key finding is hyperammonaemia. Boys with these milder forms may exhibit abnormal behaviour and be diagnosed with attention deficit hyperactivity disorder. This case illustrates how late presentation of OTC deficiency in a non-specialist centre can be difficult to differentiate from drug abuse, psychiatric illness or encephalopathy. Failure to measure blood ammonia in adults with unexplained key symptoms - particularly prolonged vomiting without diarrhoea and altered mental state/hallucinations, or to recognize the significance of elevated blood ammonia without evidence of liver decompensation can lead to delayed or missed diagnosis.

Iron deficiency anemia in inflammatory bowel disease

Science.gov (United States)

Kaitha, Sindhu; Bashir, Muhammad; Ali, Tauseef

2015-01-01

Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD. PMID:26301120

Genetics Home Reference: factor VII deficiency

Science.gov (United States)

... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

Maternal vitamin D deficiency: Fetal and neonatal implications.

Science.gov (United States)

Kovacs, Christopher S

2013-02-13

Recent research efforts have focused on the roles that vitamin D may play in skeletal and non-skeletal health during pregnancy, lactation, and fetal or neonatal development. Animal and clinical studies have shown that the mother provides calcium to the fetus and neonate without requiring vitamin D, calcitriol, or the vitamin D receptor. Consequently, the blood calcium, calciotropic hormones, and skeleton are normal at birth despite severe vitamin D deficiency or genetic deletion of calcitriol or vitamin D receptor. After birth intestinal calcium absorption becomes dependent upon calcitriol, and this is when hypocalcemia and rickets can begin to develop. Breastfed infants are at especially high risk of vitamin D deficiency due to poor penetrance of vitamin D metabolites into milk. To maximize skeletal and non-skeletal health, vitamin D dosing recommendations should ensure that the baby is born vitamin D sufficient and maintained that way during infancy and beyond. Copyright © 2013 Elsevier Ltd. All rights reserved.

Method for evaluation of risk due to seismic related design and construction errors based on past reactor experience

International Nuclear Information System (INIS)

Gonzalez Cuesta, M.; Okrent, D.

1985-01-01

This paper proposes a methodology for quantification of risk due to seismic related design and construction errors in nuclear power plants, based on information available on errors discovered in the past. For the purposes of this paper, an error is defined as any event that causes the seismic safety margins of a nuclear power plant to be smaller than implied by current regulatory requirements and industry common practice. Also, the actual reduction in the safety margins caused by the error will be called a deficiency. The method is based on a theoretical model of errors, called a deficiency logic diagram. First, an ultimate cause is present. This ultimate cause is consumated as a specific instance, called originating error. As originating errors may occur in actions to be applied a number of times, a deficiency generation system may be involved. Quality assurance activities will hopefully identify most of these deficiencies, requesting their disposition. However, the quality assurance program is not perfect and some operating plant deficiencies may persist, causing different levels of impact to the plant logic. The paper provides a way of extrapolating information about errors discovered in plants under construction in order to assess the risk due to errors that have not been discovered

Iron deficiency in childhood

NARCIS (Netherlands)

Uijterschout, L.

2015-01-01

Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

Science.gov (United States)

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Medication adherence to oral iron therapy in patients with iron deficiency anemia

Science.gov (United States)

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

2016-01-01

Objective: This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. Methods: A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Results: Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Conclusion: Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment. PMID:27375698

Vitamin D and iron deficiencies in children and adolescents with cerebral palsy.

Science.gov (United States)

Le Roy, C; Barja, S; Sepúlveda, C; Guzmán, M L; Olivarez, M; Figueroa, M J; Alvarez, M

2018-01-13

Children and adolescents with cerebral palsy (CP) are at a greater risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can study and treat are vitaminD (VD) and iron deficiencies; however, no studies have described these deficiencies in Chile. To describe the status of VD and iron in patients with CP and evaluate the relationship with certain factors associated with deficiencies of these micronutrients. We performed a descriptive, cross-sectional study including 69 patients aged between 2 and 21years, from two public hospitals. Data were obtained on demographic variables, motor function, use of feeding tube, and pharmacological treatment. We performed a nutritional assessment according to patterns of CP and determined 25-hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. Patients' mean age was 11.1±4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to-severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4% were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%) and 4 patients (6.2%) received VD and iron supplementation, respectively. Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3±8.8ng/mL; 33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients (52.2%) had low ferritin levels. There was no association between 25(OH)D level and the other variables studied. Low ferritin levels were found to be associated with older age (P=.03), being male (P=.006), and feeding tube use (P=.006). The patients studied mainly had moderate-to-severe CP, with a high frequency of suboptimal VD values and low plasma ferritin; few patients received VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels due to the high rate of deficiency of these nutrients; public hospitals should be equipped with drugs to treat these deficiencies. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights

Quantitative limitations to photosynthesis in K deficient sunflower and their implications on water-use efficiency.

Science.gov (United States)

Jákli, Bálint; Tavakol, Ershad; Tränkner, Merle; Senbayram, Mehmet; Dittert, Klaus

2017-02-01

Potassium (K) is crucial for crop growth and is strongly related to stress tolerance and water-use efficiency (WUE). A major physiological effect of K deficiency is the inhibition of net CO 2 assimilation (A N ) during photosynthesis. Whether this reduction originates from limitations either to photochemical energy conversion or biochemical CO 2 fixation or from a limitation to CO 2 diffusion through stomata and the leaf mesophyll is debated. In this study, limitations to photosynthetic carbon gain of sunflower (Helianthus annuus L.) under K deficiency and PEG- induced water deficit were quantified and their implications on plant- and leaf-scale WUE (WUE P , WUE L ) were evaluated. Results show that neither maximum quantum use efficiency (F v /F m ) nor in-vivo RubisCo activity were directly affected by K deficiency and that the observed impairment of A N was primarily due to decreased CO 2 mesophyll conductance (g m ). K deficiency additionally impaired leaf area development which, together with reduced A N , resulted in inhibition of plant growth and a reduction of WUE P . Contrastingly, WUE L was not affected by K supply which indicated no inhibition of stomatal control. PEG-stress further impeded A N by stomatal closure and resulted in enhanced WUE L and high oxidative stress. It can be concluded from this study that reduction of g m is a major response of leaves to K deficiency, possibly due to changes in leaf anatomy, which negatively affects A N and contributes to the typical symptoms like oxidative stress, growth inhibition and reduced WUE P . Copyright © 2016 Elsevier GmbH. All rights reserved.

Anemia and iron deficiency in gastrointestinal and liver conditions

Science.gov (United States)

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-01-01

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice. PMID:27672287

Successful efforts toward elimination iodine deficiency disorders in India

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Kapil Umesh

2010-01-01

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

Anemia and iron deficiency in gastrointestinal and liver conditions.

Science.gov (United States)

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-09-21

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.

Anesthetic Management of a Pediatric Patient with Arginase Deficiency

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Abdulkadir Atım

2011-09-01

Full Text Available Arginase deficiency is an autosomal recessive disorder of the urea cycle in which a defect in conversion of arginine to urea and ornithine leads to hyperammonemia. Patients with urea cycle disorders may show increased protein catabolism due to inadequate intake of energy, protein and essential amino acids; infections, fever and surgery. A 12-year-old girl with arginase deficiency, ASA II who weighed 40 kg was scheduled for bilateral adductor, quadriceps and gastrocnemius tenotomies. She had mental retardation, spasticity and flexion posture of thelower limbs. Metabolic homeostasis was restored with appropriate diet. Successful anesthetic management allowed the patient to be discharged 48 hours after surgery. Increased levels of arginine and ammonia during or after surgery may lead to serious complications such as hypotension, cerebral edema, convulsions, hypothermia and spasticity. Thus special attention must be given to metabolic homeostasis and nutrition of the patients with arginase deficiency in the perioperative period. Primary goals should be to minimize stress levels by effective anxiolysis, provide an adequate amount of protein-free energy with proper fluid management and to obtain an effective preemptive and postoperative analgesia. In addition to a high level of knowledge, successful anesthesia requires professional communication among nursing staff, dietitians, pediatric metabolism specialist, surgeon and anesthesiologist.

Diagnostic Value of the Cobalt (58Co) Excretion Test in Iron Deficiency Anemia

International Nuclear Information System (INIS)

Sihn, Hyun Chung; Hong, Kee Suck; Cho, Kyung Sam; Song, In Kyung; Koh, Chang Soon; Lee, Mun Ho

1976-01-01

The diagnosis of iron deficiency rests upon the correct evaluation of body iron stores. Morphological interpretation of blood film and the red cell indices are not reliable and often absent in mild iron deficiency. Serum iron levels and iron-binding capacity are more sensitive indices of iron deficiency, but they are often normal in iron depletion and mild iron deficiency anemia. They are also subject ro many variables which may introduce substantial errors and influenced by many pathologic and physiologic states. Examination of the bone marrow aspirate for stainable iron has been regarded as one of the most sensitive and reliable diagnostic method for detecting iron deficiency, but this also has limitations. Thus, there is still need for a more practical, but sensitive and reliable substitute as a screening test of iron deficiency. Pollack et al. (1965) observed that the intestinal absorption of cobalt was raised in iron, deficient rats and Valberg et al. (1969) found that cobalt absorption was elevated in patients with iron deficiency. A direct correlation was demonstrated between the amounts of radioiron and radiocobalt absorbed. Unlike iron, excess cobalt was excreted by the kidney, the percentage of radioactivity in the urine being directly related to the percentage absorbed from the gastro-intestinal tract. Recently a test based on the urinary excretion of an oral dose of 57 Co has been proposed as a method for detecting iron deficiency. To assess the diagnostic value of urinary cobalt excretion test cobaltous chloride labelled with 1 μCi of 58 Co was given by mouth and the percentage of the test dose excreted in the urine was measured by a gamma counter. The mean 24 hour urinary cobalt excretion in control subjects with normal iron stores was 6.1%(1.9-15.2%). Cobalt excretion was markedly increased in patients with iron deficiency and excreted more than 29% of the dose. In contrast, patients with anemia due to causes other than iron deficiency excreted less

POTENTIAL DEFICIENCIES IN EDUCATION, INSTRUMENTATION, AND WARNINGS FOR LOCALLY GENERATED TSUNAMIS

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Daniel A. Walker

2010-01-01

Full Text Available A review of historical data for Hawaii reveals that significant tsunamis have been reported for only four of twenty-six potentially tsunamigenic earthquakes from 1868 through 2009 with magnitudes of 6.0 or greater. During the same time period, three significant tsunamis have been reported for substantially smaller earthquakes. This historical perspective, the fact that the last significant local tsunami occurred in 1975, and an understandable preoccupation with tsunamis generated around the margins of the Pacific, all combine to suggest apparent deficiencies in: (1 personal awareness of what to do in the event of a possible local tsunami; (2 the distribution of instrumentation capable of providing rapid confirmation that a local tsunami has been generated; and (3 the subsequent issuance of timely warnings for local tsunamis. With these deficiencies, far more lives may be lost in Hawaii due to local tsunamis than will result from tsunamis that have originated along the margins of the Pacific. Similar deficiencies may exist in other areas of the world threatened by local tsunamis.

Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

DEFF Research Database (Denmark)

Smelt, A H; Poorthuis, B J; Onkenhout, W

1998-01-01

Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade......Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9......), tetradecadienoic acid, 14:2(n-6), and hexadecadienoic acid, 16:2(n-6). Palmitoyl-CoA and behenoyl-CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may...... be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis....

Zinc: physiology, deficiency, and parenteral nutrition.

Science.gov (United States)

Livingstone, Callum

2015-06-01

The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing. Mild deficiency that is not clinically overt may still cause nonspecific consequences, such as susceptibility to infection and poor growth. The plasma Zn concentration has poor sensitivity and specificity as a test of deficiency. Consequently, diagnosis of deficiency requires a combination of clinical assessment and biochemical tests. Patients receiving parenteral nutrition (PN) are susceptible to Zn deficiency and its consequences. Nutrition support teams should have a strategy for assessing Zn status and optimizing this by appropriate supplementation. Nutrition guidelines recommend generous Zn provision from the start of PN. This review covers the physiology of Zn, the consequences of its deficiency, and the assessment of its status, before discussing its role in PN. © 2015 American Society for Parenteral and Enteral Nutrition.

High Prevalence of Vitamin B12 Deficiency and No Folate Deficiency in Young Children in Nepal

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Bernadette N. Ng’eno

2017-01-01

Full Text Available Many children in low- and middle-income countries may have inadequate intake of vitamin B12 and folate; data confirming these inadequacies are limited. We used biochemical, demographic, behavioral and anthropometric data to describe the folate and vitamin B12 concentrations among six- to 23-month-old Nepalese children. Vitamin B12 (serum B12 < 150 pmol/L and folate deficiencies (red blood cell (RBC folate < 226.5 nmol/L were assessed. We used logistic regression to identify predictors of vitamin B12 deficiency. The vitamin B12 geometric mean was 186 pmol/L; 30.2% of children were deficient. The mean RBC folate concentration was 13,612 nmol/L; there was no deficiency. Factors associated with vitamin B12 deficiency included: (a age six to 11 months (adjusted odds ratio (aOR 1.51; 95% confidence interval (CI: 1.18, 1.92 or 12–17 months (aOR 1.38; 95% CI: 1.10, 1.72 compared to 18–23 months; (b being stunted (aOR 1.24; 95% CI: 1.03, 1.50 compared to not being stunted; (c and not eating animal-source foods (aOR 1.85; 95% CI: 1.42, 2.41 compared to eating animal-source foods the previous day. There was a high prevalence of vitamin B12 deficiency, but no folate deficiency. Improving early feeding practices, including the consumption of rich sources of vitamin B12, such as animal-source foods and fortified foods, may help decrease deficiency.

Deficiência nutricional em plântulas de feijão-de-corda decorrente da omissão de macro e micronutrientes Nutritional deficiency in cowpea seedlings due to omission of macro and micronutrients

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Rafael de Souza Miranda

2010-09-01

Full Text Available O feijão-de-corda [Vigna unguiculata (L. Walp] cv. Pitiúba é uma importante cultura nos âmbitos econômico e social do Nordeste do Brasil, especialmente no Estado do Ceará, que é considerado o maior produtor desta região. Com a finalidade de caracterizar os sintomas de deficiências nutricionais em plântulas de feijão-de-corda, as sementes foram semeadas em areia exaustivamente lavada e, após um período de cinco dias, as plântulas foram transferidas para uma solução nutritiva completa para o período de aclimatação. Após três dias, as plântulas foram submetidas aos diferentes tratamentos. O experimento teve os seguintes tratamentos: solução nutritiva completa (N; P; K; Ca; Mg; S e micronutrientes e omissão individual de cada elemento -N; -P; -K; -Ca; -Mg; -S; -B; -Fe, bem como ausência de aeração. Os sintomas das deficiências foram observados, caracterizados e registrados por fotografias. No final do experimento, as medidas de comprimento e os teores de matérias fresca e seca das raízes e parte aérea das plântulas foram analisados. Todos os macros e micronutrientes causaram sintomas de deficiência e afetaram o desenvolvimento das plântulas. Os sintomas foram desenvolvidos primeiramente em plântulas com carência em Fe, Ca e N. A matéria seca total foi reduzida em todos os tratamentos com ausência de nutrientes. A ausência de Ca, N e Fe foi responsável por uma maior redução da biomassa. A ordem decrescente de redução foi a seguinte: Ca > N > Fe > P > K > Mg > S > Aeração > B > Completo.The Cowpea [Vigna unguiculata (L. Walp] cv. Pitiúba is an important crop in the economic and social contexts in the Northeast of Brazil, especially in the state of Ceará, which is considered the largest producer of this region. With the purpose of characterizing the symptoms of nutritional deficiencies in Cowpea seedlings, the seeds were sowed in washed sand and, after a period of five days, the seedlings were

Clinical and Biological Manifestation of RNF168 Deficiency in Two Polish Siblings

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Barbara Pietrucha

2017-12-01

Full Text Available Germline mutations in the RING finger protein gene RNF168 have been identified in a combined immunodeficiency disorder called RIDDLE syndrome. Since only two patients have been described with somewhat different phenotypes, there is need to identify further patients. Here, we report on two Polish siblings with RNF168 deficiency due to homozygosity for a novel frameshift mutation, c.295delG, that was identified through exome sequencing. Both patients presented with immunoglobulin deficiency, telangiectasia, cellular radiosensitivity, and increased alpha-fetoprotein (AFP levels. The younger sibling had a more pronounced neurological and morphological phenotype, and she also carried an ATM gene mutation in the heterozygous state. Immunoblot analyses showed absence of RNF168 protein, whereas ATM levels and function were proficient in lymphoblastoid cells from both patients. Consistent with the absence of RNF168 protein, 53BP1 recruitment to DNA double-strand breaks (DSBs after irradiation was undetectable in lymphoblasts or primary fibroblasts from either of the two patients. γH2AX foci accumulated normally but they disappeared with significant delay, indicating a severe defect in DSB repair. A comparison with the two previously identified patients indicates immunoglobulin deficiency, cellular radiosensitivity, and increased AFP levels as hallmarks of RNF168 deficiency. The variability in its clinical expression despite similar cellular phenotypes suggests that some manifestations of RNF168 deficiency may be modified by additional genetic or epidemiological factors.

Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency.

LENUS (Irish Health Repository)

McLean, Caitriona

2009-01-01

Alpha-1 antitrypsin (A1AT) is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to <35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys). ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs) and RNA interference (RNAi), which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.

Vitamin D/dietary calcium deficiency rickets and pseudo-vitamin D deficiency rickets

Science.gov (United States)

Glorieux, Francis H; Pettifor, John M

2014-01-01

This review describes the pathogenesis, clinical presentation and biochemical perturbations found in privational (nutritional) rickets and pseudo-vitamin D deficiency rickets (PDDR), an autosomal recessive condition with loss of function mutations in CYP27B1. It may seem strange to combine a discussion on privational rickets and PDDR as a single topic, but privational rickets and PDDR present with similar clinical signs and symptoms and with similar perturbations in bone and mineral metabolism. Of interest is the characteristic lack of features of rickets at birth in infants with PDDR, a finding which has also been reported in infants born to vitamin D-deficient mothers. This highlights the independence of the fetus and neonate from the need for vitamin D to maintain calcium homeostasis during this period. The variable roles of vitamin D deficiency and dietary calcium deficiency in the pathogenesis of privational rickets are discussed and the associated alterations in vitamin D metabolism highlighted. Although PDDR is a rare autosomal recessive disorder, results of long-term follow-up are now available on the effect of treatment with calcitriol, and these are discussed. Areas of uncertainty, such as should affected mothers breastfeed their infants, are emphasized. PMID:24818008

Muscle phosphorylase kinase deficiency

DEFF Research Database (Denmark)

Preisler, N; Orngreen, M C; Echaniz-Laguna, A

2012-01-01

To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

Isolated sulfite oxidase deficiency.

Science.gov (United States)

Rupar, C A; Gillett, J; Gordon, B A; Ramsay, D A; Johnson, J L; Garrett, R M; Rajagopalan, K V; Jung, J H; Bacheyie, G S; Sellers, A R

1996-12-01

Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.

Iron deficiency in blood donors

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Rodolfo Delfini Cançado

Full Text Available CONTEXT: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. OBJECTIVE: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors, and the frequency of donations per year. DESIGN: From September 20 to October 5, 1999, three hundred blood donors from Santa Casa Hemocenter of São Paulo were studied. DIAGNOSTIC TESTS: Using a combination of biochemical measurements of iron status: serum iron, total iron-binding capacity, transferrin saturation index, serum ferritin and the erythrocyte indices. RESULTS: The frequency of iron deficiency in blood donors was 11.0%, of whom 5.5% (13/237 were male and 31.7% (20/63 female donors. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, for male blood donors (7.6% versus 0.0%, P < 0.05 and female ones (41.5% versus 18.5%, P < 0.05. The frequency of iron deficiency found was higher among the male blood donors with three or more donations per year (P < 0.05 and among the female blood donors with two or more donations per year (P < 0.05. CONCLUSIONS: We conclude that blood donation is a very important factor for iron deficiency in blood donors, particularly in multi-time donors and especially in female donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia.

Antepartum Ornithine Transcarbamylase Deficiency

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Hitoshi Nakajima

2014-11-01

Full Text Available Ornithine transcarbamylase deficiency (OTCD is the most common type urea cycle enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed with OTCD following neurocognitive deficit during her first pregnancy. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Plasma amino acid and urine organic acid analysis revealed OTCD. After combined modality treatment with arginine, sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized and her mental status returned to normal. At last she recovered without any damage left.

Glucose-6-Phosphate Dehydrogenase Deficiency and Adrenal Hemorrhage in a Filipino Neonate with Hyperbilirubinemia

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Akira Ohishi

2013-05-01

Full Text Available We report on a Filipino neonate with early onset and prolonged hyperbilirubinemia who was delivered by a vacuum extraction due to a prolonged labor. Subsequent studies revealed adrenal hemorrhage and glucose-6-phosphate dehydrogenase (G6PD deficiency. It is likely that asphyxia and resultant hypoxia underlie the occurrence of adrenal hemorrhage and the clinical manifestation of G6PD deficiency and that the presence of the two events explains the early onset and prolonged hyperbilirubinemia of this neonate. Our results represent the importance of examining possible underlying factors for the development of severe, early onset, or prolonged hyperbilirubinemia.

Iron deficiency among blood donors

DEFF Research Database (Denmark)

Rigas, A S; Pedersen, O B; Magnussen, K

2017-01-01

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation...... and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark...

Functional Capacity Evaluation in Upper Limb Reduction Deficiency and Amputation : Development and Pilot Testing

NARCIS (Netherlands)

Postema, S G; Bongers, R M; Reneman, M F; van der Sluis, C K

Purpose To develop and pilot test a functional capacity evaluation (FCE) for individuals with upper limb absence (ULA) due to reduction deficiency or amputation, and to examine the relationship between FCE results and presence of musculoskeletal complaints (MSC). Method Five tests (overhead lifting,

Deficiency indices and singular boundary conditions in quantum mechanics

International Nuclear Information System (INIS)

Bulla, W.

1984-01-01

We consider Schroedinger operators H in L 2 (Rsup(n)), n from IN, with countably infinitely many local singularities of the potential which are separated from each other by a positive distance. It is proved that due to locality each singularity yields a separate contribution to the deficiency index of H. In the special case where the singularities are pointlike and the potential exhibits certain symmetries near these points we give an explicit construction of self-adjoint boundary conditions

Iron deficiency and hematinic deficiencies in atrial fibrillation: A new insight into comorbidities.

Science.gov (United States)

Keskin, Muhammed; Ural, Dilek; Altay, Servet; Argan, Onur; Börklü, Edibe Betül; Kozan, Ömer

2018-03-01

Iron deficiency (ID) is the most common nutritional deficiency, and iron metabolism becomes further deteriorated in the presence of certain conditions, such as heart failure (HF). Atrial fibrillation (AF) has many similarities to HF, including a chronic inflammatory pathophysiology; however, the prevalence of ID and other hematinic deficiencies in AF patients have not been determined. In this study, the prevalence of iron (serum ferritin <100 µg/L or ferritin 100-299 µg/L with transferrin saturation <20%), vitamin B12 (<200 pg/mL), and folate deficiency (<4.0 ng/mL) was evaluated in 101 patients with non-valvular AF with preserved left ventricular ejection fraction and no signs of HF, and the results were compared with 35 age- and gender-matched controls. Anemia was detected in 26% of the patients. A total of 48 (47.6%) patients had ID, 10 (9.9%) had a vitamin B12 deficiency, and 13 (12.9%) had a folate deficiency. The prevalence of ID was similar in the controls and the paroxysmal AF patients, but increased gradually in persistent and permanent AF. Univariate logistic regression analysis demonstrated that permanent vs. paroxysmal AF [Odds ratio (OR): 2.17; 95% confidence interval (CI): 0.82-5.69; p=0.011], high sensitive C-reactive protein (OR: 1.47; 95% CI: 0.93-2.36; p=0.019), N-terminal pro b-type natriuretic peptide (OR: 1.24; 95% CI: 0.96-1.71; p=0.034), and white blood cell count (OR: 1.21; 95% CI: 0.95-1.58; p=0.041) were associated with ID. In multivariable analysis, permanent AF remained as an independent clinical associate of ID (OR: 4.30; 95% CI: 0.83-12.07; p=0.039). ID is common in permanent AF, as in HF. Inflammation and neurohormonal activation seem to contribute to its development.

Anterior Segment Findings in Vitamin A Deficiency: A Case Series

Directory of Open Access Journals (Sweden)

Pierangela Rubino

2015-01-01

lead to blindness for severe keratomalacia with cornea scarring and perforation or night blindness due to impaired dark adaptation. Conversely, the disease is quite common in developing countries, as a consequence of chronic malnutrition. The correct diagnosis and therapy with prompt vitamin A supplementation avoid blindness. We report a series of 3 local cases with different age and causes for vitamin A deficiency. The diagnostic workup, therapy, and prognosis are discussed.

Pulmonary and Cerebral Infarcts Due to Secondary Thrombosis Risk of a Genetic Mutation: Life-threating Methylentetrahydrofolate Reductase (MTHFR Deficiency with Early Onset

Directory of Open Access Journals (Sweden)

Ianosi Edith Simona

2016-06-01

Full Text Available Methylentetrahydrofolate reductase (MTHFR is a key enzymatic component of the folate cycle, converting 5,10-methylentetrahydrofolate into 5-methylentetrahydrofolate. Severe MTHFR deficiency is a rare recessive disease leading to major hyperhomocysteinemia, homocystinuria, and progressive neurological distress within the two first decades of life.

Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency

Directory of Open Access Journals (Sweden)

Kavya Reddy

2016-03-01

Full Text Available Attenuated auto-lysosomal system has been associated with Alzheimer disease (AD, yet all underlying molecular mechanisms leading to this impairment are unknown. We show that the amino acid sensing of mechanistic target of rapamycin complex 1 (mTORC1 is dysregulated in cells deficient in presenilin, a protein associated with AD. In these cells, mTORC1 is constitutively tethered to lysosomal membranes, unresponsive to starvation, and inhibitory to TFEB-mediated clearance due to a reduction in Sestrin2 expression. Normalization of Sestrin2 levels through overexpression or elevation of nuclear calcium rescued mTORC1 tethering and initiated clearance. While CLEAR network attenuation in vivo results in buildup of amyloid, phospho-Tau, and neurodegeneration, presenilin-knockout fibroblasts and iPSC-derived AD human neurons fail to effectively initiate autophagy. These results propose an altered mechanism for nutrient sensing in presenilin deficiency and underline an importance of clearance pathways in the onset of AD.

Genetics Home Reference: X-linked creatine deficiency

Science.gov (United States)

... Health Conditions X-linked creatine deficiency X-linked creatine deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description X-linked creatine deficiency is an inherited disorder that primarily affects ...

Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

Science.gov (United States)

... Email Facebook Twitter Home Health Conditions CACT deficiency Carnitine-acylcarnitine translocase deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that ...

A Program for Iron Economy during Deficiency Targets Specific Fe Proteins.

Science.gov (United States)

Hantzis, Laura J; Kroh, Gretchen E; Jahn, Courtney E; Cantrell, Michael; Peers, Graham; Pilon, Marinus; Ravet, Karl

2018-01-01

Iron (Fe) is an essential element for plants, utilized in nearly every cellular process. Because the adjustment of uptake under Fe limitation cannot satisfy all demands, plants need to acclimate their physiology and biochemistry, especially in their chloroplasts, which have a high demand for Fe. To investigate if a program exists for the utilization of Fe under deficiency, we analyzed how hydroponically grown Arabidopsis ( Arabidopsis thaliana ) adjusts its physiology and Fe protein composition in vegetative photosynthetic tissue during Fe deficiency. Fe deficiency first affected photosynthetic electron transport with concomitant reductions in carbon assimilation and biomass production when effects on respiration were not yet significant. Photosynthetic electron transport function and protein levels of Fe-dependent enzymes were fully recovered upon Fe resupply, indicating that the Fe depletion stress did not cause irreversible secondary damage. At the protein level, ferredoxin, the cytochrome- b 6 f complex, and Fe-containing enzymes of the plastid sulfur assimilation pathway were major targets of Fe deficiency, whereas other Fe-dependent functions were relatively less affected. In coordination, SufA and SufB, two proteins of the plastid Fe-sulfur cofactor assembly pathway, were also diminished early by Fe depletion. Iron depletion reduced mRNA levels for the majority of the affected proteins, indicating that loss of enzyme was not just due to lack of Fe cofactors. SufB and ferredoxin were early targets of transcript down-regulation. The data reveal a hierarchy for Fe utilization in photosynthetic tissue and indicate that a program is in place to acclimate to impending Fe deficiency. © 2018 American Society of Plant Biologists. All Rights Reserved.

Oral declines and mastication deficiencies cause alteration of food bolus properties.

Science.gov (United States)

Peyron, M-A; Santé-Lhoutellier, V; François, O; Hennequin, M

2018-02-21

In the elderly, masticatory function often presents failure in certain oral tasks due to impairment such as decline in muscular force, jaw or tongue motility, neuro-muscular coordination, tooth damage, malocclusion and saliva production. Great disparity is observed in the various and potentially cumulative oral declines that occur with ageing. Such difficulties may have an impact on food consumption and nutritional status. To obtain better understanding of the consequences of several oral deficiencies, a series of swallowable boluses were prepared in vitro with the AM 2 masticator apparatus with normal and deficient programming. Physiological normal mastication (NM) was simulated using in vivo data from healthy subjects. Chewing deficiencies were reproduced by alteration of NM programming to perform different levels and combinations of force loss, lack of saliva and decrease in the motility of oral elements. Poultry meatballs were used as test-food. Particle size distribution in the food bolus was measured by sieving and rheological features (hardness, cohesiveness and elasticity) were assessed with a TPA test. Compared to the NM outcome, significant and gradual deterioration of the food bolus was observed and associated with alteration in force, saliva and motility. Combinations of several failures led to greater or cumulative deficiencies in swallowable bolus properties. For the elderly presenting a high prevalence of various oral injuries, tailoring textured food cannot be ignored as a solution for remedying deficiencies and favoring the formation of a safe-swallowable bolus, which is an essential vector of nutrients. Knowing the impacts of oral injuries on the food bolus is obviously a requisite for developing diet strategies, including nutritional items for specific populations.

Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report.

Science.gov (United States)

Stephen, Joshi; Nampoothiri, Sheela; Vinayan, K P; Yesodharan, Dhanya; Remesh, Preetha; Gahl, William A; Malicdan, May Christine V

2018-05-16

Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy. The study describes a male child from consanguineous family presented with hypofibrinogenemia, diffuse cortical atrophy, microcephaly, hypertonia and axonal motor neuropathy. Through a combination of homozygosity mapping and exome sequencing, we identified bi-allelic pathogenic mutations in two genes: a homozygous novel truncating mutation in FGG (c.554del; p.Lys185Argfs*14) and a homozygous missense mutation in TBCD (c.1423G > A;p.Ala475Thr). Loss of function mutations in FGG have been associated with fibrinogen deficiency, while the c.1423G > A mutation in TBCD causes a novel syndrome of neurodegeneration and early onset encephalopathy. Our study highlights the importance of homozygosity mapping and exome sequencing in molecular prenatal diagnosis, especially when multiple gene mutations are responsible for the phenotype.

Iron deficiency - a global problem

International Nuclear Information System (INIS)

Ali, S.M.

1993-01-01

Iron deficiency is an important nutritional global problem. This paper contains summery of information gathered from a dietary survey as iron deficiency anaemia is major public health problem in many developing countries including Pakistan. Comparison of anaemia in different age group and sex versus various regions in the world are given. In Pakistan also anaemia is widespread. According to the report of Micro-Nutrient survey of Pakistan 40% of the population are found to have low level of haemoglobin, more than half of pregnant women suffered from marginal or deficient haemoglobin. (A.B.)

Iron deficiency - a global problem

Energy Technology Data Exchange (ETDEWEB)

Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

1994-12-31

Iron deficiency is an important nutritional global problem. This paper contains summery of information gathered from a dietary survey as iron deficiency anaemia is major public health problem in many developing countries including Pakistan. Comparison of anaemia in different age group and sex versus various regions in the world are given. In Pakistan also anaemia is widespread. According to the report of Micro-Nutrient survey of Pakistan 40% of the population are found to have low level of haemoglobin, more than half of pregnant women suffered from marginal or deficient haemoglobin. (A.B.).

Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease: A Systematic Review.

Science.gov (United States)

Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

2015-06-01

Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron.

Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping

DEFF Research Database (Denmark)

Madsen, Pia Pinholt

2006-01-01

Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of L: -isoleucine catabolism. Little is known about the clinical presentation associated with this enzyme defect, as it has been reported in only a limited number of patients. Because the presence...... is relevant to the interpretation of the functional consequences of this type of mutation in other disease genes....

Genetics Home Reference: CDKL5 deficiency disorder

Science.gov (United States)

... Facebook Twitter Home Health Conditions CDKL5 deficiency disorder CDKL5 deficiency disorder Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description CDKL5 deficiency disorder is characterized by seizures that begin ...

Sleep and Neurofunctions Throughout Child Development: Lasting Effects of Early Iron Deficiency

Science.gov (United States)

Peirano, Patricio D.; Algarín, Cecilia R.; Chamorro, Rodrigo; Garrido, Marcelo I.; Lozoff, Betsy

2013-01-01

Iron-deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. Infants are at particular risk due to rapid growth and limited dietary sources of iron. An estimated 20–25% of the world’s infants have IDA, with at least as many having iron deficiency without anemia. High prevalence is found primarily in developing countries, but also among poor, minority, and immigrant groups in developed ones. Infants with IDA test lower in mental and motor development assessments and show affective differences. After iron therapy, follow-up studies point to long-lasting differences in several domains. Neurofunctional studies showed slower neural transmission in the auditory system despite 1 year of iron therapy in IDA infants; they still had slower transmission in both the auditory and visual systems at preschool age. Different motor activity patterning in all sleep-waking states and several differences in sleep states organization were reported. Persistant sleep and neurofunctional effects could contribute to reduced potential for optimal behavioral and cognitive outcomes in children with a history of IDA. PMID:19214058

Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lepob/ob mice

International Nuclear Information System (INIS)

Sekiya, Motohiro; Yahagi, Naoya; Tamura, Yoshiaki; Okazaki, Hiroaki; Igarashi, Masaki; Ohta, Keisuke; Takanashi, Mikio; Kumagai, Masayoshi; Takase, Satoru; Nishi, Makiko; Takeuchi, Yoshinori; Izumida, Yoshihiko; Kubota, Midori; Ohashi, Ken; Iizuka, Yoko; Yagyu, Hiroaki; Gotoda, Takanari; Nagai, Ryozo; Shimano, Hitoshi; Yamada, Nobuhiro

2009-01-01

It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic β-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lep ob/ob /HSL -/- ) and explored the role of HSL in pancreatic β-cells in the setting of obesity. Lep ob/ob /HSL -/- developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep ob/ob /HSL +/+ in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep +/+ background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep ob/ob islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep ob/ob mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.

Building public trust: Actions to respond to the report of the Advisory Committee on human radiation experiments

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-03-01

Democratic government requires trust: people need to know and believe that the government is telling the truth. Without information about what the government is doing and why, citizens cannot exercise democratic control over government institutions. During his first year in office, President Clinton became concerned about reports that the government had conducted unethical secret human radiation experiments during the Cold War. To address this issue, in January 1994, President Clinton established the Advisory Committee on Human Radiation Experiments (ACHRE), chaired by bioethicist Dr. Ruth Faden of Johns Hopkins University. The President also directed all Federal agencies to search for records related to human subjects radiation research and provide them to the Advisory Committee. This report presents the Administration`s actions to respond to the ACHRE`s findings and recommendations.

Iron deficiency anaemia among apparently healthy pre-school ...

African Journals Online (AJOL)

Background: Iron deficiency, and specifically iron deficiency anaemia, remains one of the most severe and important nutritional deficiencies in the world today. Objective: To estimate the prevalence and associated factors for iron deficiency anaemia among pre-school children in Lagos. Methodology: The study was ...

Genetics Home Reference: corticosterone methyloxidase deficiency

Science.gov (United States)

... hyperreninemic hypoaldosteronism steroid 18-hydroxylase deficiency steroid 18-oxidase deficiency Visser-Cost syndrome ... Potassium Test Health Topic: Adrenal Gland Disorders Health Topic: Fluid ...

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency

OpenAIRE

Garone, Caterina; Garc??a-D??az, Beatriz; Emmanuele, Valentina; L??pez Garc??a, Luis Carlos; Tadesse, Saba; Akman, Hasan O.; Tanji, Kurenai; Quinzii, Catarina M.; Hirano, Michio

2014-01-01

Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2 −/− ) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-...

Prevalence and factors promoting the occurrence of vitamin D deficiency in the elderly.

Science.gov (United States)

Wyskida, Magdalena; Wieczorowska-Tobis, Katarzyna; Chudek, Jerzy

2017-03-13

Vitamin D deficiency affects a large part of the population of elderly people, especially women, who live in moderate climate countries due to a reduced amount of vitamin D in the diet (small sea fish consumption) and reduced content of 7-dehydrocholesterol, which causes decreased skin synthesis. The lowest seasonal concentration of 25(OH)D3 is usually observed during winter and spring. Sun exposure influences 25(OH)D3 concentration more strongly in men than in women. Sociodemographic factors that increase the risk of vitamin D deficiency in the elderly include poor environmental conditions, low economic status, lower educational level, drug exposure (smoking), reduced physical activity, overall poor health and obesity, which causes reduced skin exposure to sunlight. The use of medications or supplements that contain vitamin D and staying in a nursing home that employ such supplementation are factors that prevent deficiency. Significant prevalence of diseases of the gastrointestinal tract may contribute to cholecalciferol and ergocalciferol malabsorption or impair their liver transformation. In addition, the high incidence of chronic kidney disease in old age reduces processing hydroxylation of vitamin D and the formation of active metabolites. Vitamin D deficiency can not only cause bone mineralization disorders, but also increase incidence of cardiovascular diseases, cancers, type 2 diabetes and depression. The aim of this study was to summarize current knowledge about the risk factors of vitamin D deficiency development in the elderly population.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

Directory of Open Access Journals (Sweden)

Jung Hyun Park

2017-01-01

Full Text Available Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2 regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA- transfected Lewis lung carcinoma (LLC cells and idh2-deficient (idh2−/− mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2−/− mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration.

Science.gov (United States)

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP + -dependent isocitrate dehydrogenase ( idh2 ) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and idh2 -deficient ( idh2 -/- ) mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2 -/- mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Dietary Selenium Deficiency Exacerbates DSS-Induced Epithelial Injury and AOM/DSS-Induced Tumorigenesis

Science.gov (United States)

Barrett, Caitlyn W.; Singh, Kshipra; Motley, Amy K.; Lintel, Mary K.; Matafonova, Elena; Bradley, Amber M.; Ning, Wei; Poindexter, Shenika V.; Parang, Bobak; Reddy, Vishruth K.; Chaturvedi, Rupesh; Fingleton, Barbara M.; Washington, Mary K.; Wilson, Keith T.; Davies, Sean S.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

2013-01-01

Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation. In order to better understand the role of Se in epithelial injury and tumorigenesis resulting from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or -sufficient mice in response to dextran sodium sulfate (DSS)-induced colitis, and azoxymethane (AOM) followed by cyclical administration of DSS, respectively. In response to DSS alone, Se-deficient mice demonstrated increased morbidity, weight loss, stool scores, and colonic injury with a concomitant increase in DNA damage and increases in inflammation-related cytokines. As there was an increase in DNA damage as well as expression of several EGF and TGF-β pathway genes in response to inflammatory injury, we sought to determine if tumorigenesis was altered in the setting of inflammatory carcinogenesis. Se-deficient mice subjected to AOM/DSS treatment to model colitis-associated cancer (CAC) had increased tumor number, though not size, as well as increased incidence of high grade dysplasia. This increase in tumor initiation was likely due to a general increase in colonic DNA damage, as increased 8-OHdG staining was seen in Se-deficient tumors and adjacent, non-tumor mucosa. Taken together, our results indicate that Se deficiency worsens experimental colitis and promotes tumor development and progression in inflammatory carcinogenesis. PMID:23861820

New structural and functional defects in polyphosphate deficient bacteria: A cellular and proteomic study

Directory of Open Access Journals (Sweden)

Chávez Francisco P

2010-01-01

Full Text Available Abstract Background Inorganic polyphosphate (polyP, a polymer of tens or hundreds of phosphate residues linked by ATP-like bonds, is found in all organisms and performs a wide variety of functions. PolyP is synthesized in bacterial cells by the actions of polyphosphate kinases (PPK1 and PPK2 and degraded by exopolyphosphatase (PPX. Bacterial cells with polyP deficiencies due to knocking out the ppk1 gene are affected in many structural and important cellular functions such as motility, quorum sensing, biofilm formation and virulence among others. The cause of this pleiotropy is not entirely understood. Results The overexpression of exopolyphosphatase in bacteria mimicked some pleitropic defects found in ppk1 mutants. By using this approach we found new structural and functional defects in the polyP-accumulating bacteria Pseudomonas sp. B4, which are most likely due to differences in the polyP-removal strategy. Colony morphology phenotype, lipopolysaccharide (LPS structure changes and cellular division malfunction were observed. Finally, we used comparative proteomics in order to elucidate the cellular adjustments that occurred during polyP deficiency in this bacterium and found some clues that helped to understand the structural and functional defects observed. Conclusions The results obtained suggest that during polyP deficiency energy metabolism and particularly nucleoside triphosphate (NTP formation were affected and that bacterial cells overcame this problem by increasing the flux of energy-generating metabolic pathways such as tricarboxilic acid (TCA cycle, β-oxidation and oxidative phosphorylation and by reducing energy-consuming ones such as active transporters and amino acid biosynthesis. Furthermore, our results suggest that a general stress response also took place in the cell during polyP deficiency.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Yan, Jidong [Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Xu, Jing [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Fei, Yao [College of Life Sciences, Northwest University, Xi’an, Shaanxi Province 710069 (China); Jiang, Congshan; Zhu, Wenhua; Han, Yan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Lu, Shemin, E-mail: lushemin@xjtu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China (China)

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

Vitamin D deficiency rickets in an adolescent with severe atopic dermatitis.

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Borzutzky, Arturo; Grob, Francisca; Camargo, Carlos A; Martinez-Aguayo, Alejandro

2014-02-01

Atopic dermatitis (AD) affects 10% to 20% of children worldwide. Its severity may be inversely correlated with 25-hydroxyvitamin D (25OHD) levels. Although low levels of vitamin D (VD) can cause rickets in infants, VD deficiency rickets is an unusual presentation in teenagers. We report the case of a 14-year-old girl with severe AD and fish allergy since early childhood. She lived at high latitude (with less sun exposure) and, because of her atopic disorders, avoided sunlight and fish. Laboratory studies showed elevated alkaline phosphatase and parathyroid hormone levels and low serum calcium; her serum 25OHD level was rickets due to VD deficiency. Treatment with VD increased her 25OHD level to 44 nmol/L, with normalization of alkaline phosphatase, parathyroid hormone, and calcium. Moreover, we observed a dramatic improvement in her AD severity with VD treatment. This case demonstrates the complex interaction between VD deficiency, AD, and food allergy. We advise a high index of suspicion of VD deficiency rickets in children of all ages with AD, particularly during accelerated growth periods and in the presence of other risk factors such as darker skin, living at high latitude, sun avoidance, and low intake of VD-rich foods. The concomitant improvement in bone-related parameters and AD severity may reflect a double benefit of VD treatment, a possibility that warrants research on VD as potential treatment for AD.

The co-occurrence of zinc deficiency and social isolation has the opposite effects on mood compared with either condition alone due to changes in the central norepinephrine system.

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Mitsuya, Hironori; Omata, Naoto; Kiyono, Yasushi; Mizuno, Tomoyuki; Murata, Tetsuhito; Mita, Kayo; Okazawa, Hidehiko; Wada, Yuji

2015-05-01

Nutritional and social environmental problems during the early stages of life are closely associated with the pathophysiology of mood disorders such as depression. Disruption or dysfunction of the central norepinephrine (NE) system is also considered to play a role in mood disorders. Therefore, we evaluated the effects of zinc deficiency and/or social isolation on mood and changes in the central NE system using rats. Compared with the controls, the rats subjected to zinc deficiency or social isolation alone exhibited increased anxiety-related behavior in the elevated plus maze and greater depression-like behavior in the forced swim test. However, the co-occurrence of zinc deficiency and social isolation resulted in decreased anxiety-related behavior and control levels of depression-like behavior. Social isolation alone decreased the rats' cerebral NE concentrations. The expression of the NE transporter was not affected by social isolation alone, but its expression in the locus coeruleus was markedly decreased by the co-occurrence of social isolation and zinc deficiency, and this change was accompanied by an increase in the blood concentration of 3-methoxy-4-hydroxyphenylglycol, which is a marker of central NE system activity. These findings suggest that zinc deficiency or social isolation alone induce anxious or depressive symptoms, but the presence of both conditions has anxiolytic or antidepressive effects. Furthermore, these opposing effects of mood-related behaviors were found to be associated with changes in the central NE system. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection

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Kempashanaiah Nanjundappa

2011-08-01

Full Text Available Abstract Background Interest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens. However, the use of bacteriophages for therapeutic purposes has raised concerns over the potential for immune response, rapid toxin release by the lytic action of phages, and difficulty in dose determination in clinical situations. A phage that kills the target cell but is incapable of host cell lysis would alleviate these concerns without compromising efficacy. Results We developed a recombinant lysis-deficient Staphylococcus aureus phage P954, in which the endolysin gene was rendered nonfunctional by insertional inactivation. P954, a temperate phage, was lysogenized in S. aureus strain RN4220. The native endolysin gene on the prophage was replaced with an endolysin gene disrupted by the chloramphenicol acetyl transferase (cat gene through homologous recombination using a plasmid construct. Lysogens carrying the recombinant phage were detected by growth in presence of chloramphenicol. Induction of the recombinant prophage did not result in host cell lysis, and the phage progeny were released by cell lysis with glass beads. The recombinant phage retained the endolysin-deficient genotype and formed plaques only when endolysin was supplemented. The host range of the recombinant phage was the same as that of the parent phage. To test the in vivo efficacy of the recombinant endolysin-deficient phage, immunocompromised mice were challenged with pathogenic S. aureus at a dose that results in 80% mortality (LD80. Treatment with the endolysin-deficient phage rescued mice from the fatal S. aureus infection. Conclusions A recombinant endolysin-deficient staphylococcal phage has been developed that is lethal to methicillin-resistant S. aureus without causing bacterial cell lysis. The phage was able to multiply in lytic mode utilizing a heterologous endolysin expressed from a plasmid in the propagation host

Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

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Oosterveer Maaike H

2011-12-01

Full Text Available Abstract Background Overactivity and/or dysregulation of the endocannabinoid system (ECS contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1 in adipocyte function and CB1-receptor deficient (CB1-/- mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown. Methods We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB1-/- and CB1+/+ mice fed a high-fat (HF or a high-fat/fish oil (HF/FO diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB1 functioning. Results The adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL activities were also not altered in CB1-/- mice. Conclusions These findings indicate that protection against diet-induced adiposity in CB1-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.

The "multiple hormone deficiency" theory of aging: is human senescence caused mainly by multiple hormone deficiencies?

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Hertoghe, T

2005-12-01

In the human body, the productions, levels and cell receptors of most hormones progressively decline with age, gradually putting the body into various states of endocrine deficiency. The circadian cycles of these hormones also change, sometimes profoundly, with time. In aging individuals, the well-balanced endocrine system can fall into a chaotic condition with losses, phase-advancements, phase delays, unpredictable irregularities of nycthemeral hormone cycles, in particular in very old or sick individuals. The desynchronization makes hormone activities peak at the wrong times and become inefficient, and in certain cases health threatening. The occurrence of multiple hormone deficits and spilling through desynchronization may constitute the major causes of human senescence, and they are treatable causes. Several arguments can be put forward to support the view that senescence is mainly a multiple hormone deficiency syndrome: First, many if not most of the signs, symptoms and diseases (including cardiovascular diseases, cancer, obesity, diabetes, osteoporosis, dementia) of senescence are similar to physical consequences of hormone deficiencies and may be caused by hormone deficiencies. Second, most of the presumed causes of senescence such as excessive free radical formation, glycation, cross-linking of proteins, imbalanced apoptosis system, accumulation of waste products, failure of repair systems, deficient immune system, may be caused or favored by hormone deficiencies. Even genetic causes such as limits to cell proliferation (such as the Hayflick limit of cell division), poor gene polymorphisms, premature telomere shortening and activation of possible genetic "dead programs" may have links with hormone deficiencies, being either the consequence, the cause, or the major favoring factor of hormone deficiencies. Third, well-dosed and -balanced hormone supplements may slow down or stop the progression of signs, symptoms, or diseases of senescence and may often

Hematopoietic studies in vitamin A deficiency.

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Hodges, R E; Sauberlich, H E; Canham, J E; Wallace, D L; Rucker, R B; Mejia, L A; Mohanram, M

1978-05-01

Recent studies of experimental vitamin A deficiency in man led the authors to conclude that anemia may result from lack of vitamin A. A review of numerous nutrition surveys in underdeveloped countries enhanced the suspicion that deficiency of vitamin A does contribute to the prevalence of anemia. Preliminary studies of vitamin A-deficient rats confirmed previous observations that anemia may result from lack of this vitamin. The livers of these animals had very low concentrations of vitamin A but normal or increased concentrations of iron. The finding of anemia is in contrast with other reports that vitamin A deficiency may cause elevated values for hemoglobin and hematocrit. The authors suggest that loss of taste and smell as a result of deficiency may account for refusal of experimental animals to eat and drink enough to prevent inanitation and dehydration. The resulting hemoconcentration may mask the true hematological picture, which is one of anemia.

Familial glucocorticoid deficiency presenting with generalized hyperpigmentation in an Egyptian child: a case report

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Metwalley Kotb A

2012-04-01

Full Text Available Abstract Introduction Familial glucocorticoid deficiency, or hereditary unresponsiveness to adrenocorticotropic hormone, is a rare autosomal recessive disease characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency. It may present in infancy or early childhood with hyperpigmentation, failure to thrive, recurrent infections, hypoglycemic attacks and convulsions that may result in coma or death. Here, we report the case of an 18-month-old Egyptian boy with familial glucocorticoid deficiency. Case presentation An 18-month-old Egyptian boy was referred to our institution for evaluation of generalized hyperpigmentation of the body associated with recurrent convulsions; one of his siblings, who had died at the age of nine months, also had generalized hyperpigmentation of the body. The initial clinical examination revealed generalized symmetrical deep hyperpigmentation of the body as well as hypotonia, normal blood pressure and normal male genitalia. He had low blood glucose and cortisol levels, normal aldosterone and high adrenocorticotropic hormone levels. Based on the above mentioned data, a provisional diagnosis of familial glucocorticoid deficiency was made, which was confirmed by a molecular genetics study. Oral hydrocortisone treatment at a dose of 10 mg/m2/day was started. The child was followed up after two months of treatment; the hyperpigmentation has lessened in comparison with his initial presentation and his blood sugar and cortisol levels were normalized. Conclusion Familial glucocorticoid deficiency is a rare, treatable disease that can be easily missed due to nonspecific presentations. The consequences of delayed diagnosis and treatment are associated with high rates of morbidity and mortality.

MCPIP1 deficiency in mice results in severe anemia related to autoimmune mechanisms.

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Zhou Zhou

Full Text Available Autoimmune gastritis is an organ-specific autoimmune disease of the stomach associated with pernicious anemia. The previous work from us and other groups identified MCPIP1 as an essential factor controlling inflammation and immune homeostasis. MCPIP1(-/- developed severe anemia. However, the mechanisms underlying this phenotype remain unclear. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the erythropoiesis in MCPIP1(-/- bone marrow erythroblasts was significantly attenuated due to iron and vitamin B12 (VB12 deficiency, which was mainly resulted from autoimmunity-associated gastritis and parietal cell loss. Consistently, exogenous supplement of iron and VB12 greatly improved the anemia phenotype of MCPIP1(-/- mice. Finally, we have evidence suggesting that autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1(-/- mice. Taken together, our study suggests that MCPIP1 deficiency in mice leads to the development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1(-/- mice may be a good mouse model for investigating the pathogenesis of pernicious anemia and testing the efficacy of some potential drugs for treatment of this disease.

Glucose-6-phosphate dehydrogenase deficiency and Alzheimer's disease: Partners in crime? The hypothesis.

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Ulusu, N Nuray

2015-08-01

Alzheimer's disease is a multifaceted brain disorder which involves various coupled irreversible, progressive biochemical reactions that significantly reduce quality of life as well as the actual life expectancy. Aging, genetic predispositions, head trauma, diabetes, cardiovascular disease, deficiencies in insulin signaling, dysfunction of mitochondria-associated membranes, cerebrovascular changes, high cholesterol level, increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic dysfunction, high blood pressure, obesity, dietary habits, exercise, social engagement, and mental stress are noted among the risk factors of this disease. In this hypothesis review I would like to draw the attention on glucose-6-phosphate dehydrogenase deficiency and its relationship with Alzheimer's disease. This enzymopathy is the most common human congenital defect of metabolism and defined by decrease in NADPH+H(+) and reduced form of glutathione concentration and that might in turn, amplify oxidative stress due to essentiality of the enzyme. This most common enzymopathy may manifest itself in severe forms, however most of the individuals with this deficiency are not essentially symptomatic. To understand the sporadic Alzheimer's disease, the writer of this paper thinks that, looking into a crystal ball might not yield much of a benefit but glucose-6-phosphate dehydrogenase deficiency could effortlessly give some clues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Common micronutrient deficiencies among food aid beneficiaries ...

African Journals Online (AJOL)

Results: Vitamin A and iron deficiencies were the most prevalent micronutrient deficiencies among food aid beneficiaries. Other probable deficiencies prevailing were zinc, vitamins thiamine, riboflavin, niacin folate, cyano-cobalamine, ascorbic acid vitamin D and calcium because of the low intake of dairy products and meat.

Relationship Between Vitamin D Deficiency and Markers of Metabolic Syndrome Among Overweight and Obese Adults.

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Kaseb, Fatemeh; Haghighyfard, Kimia; Salami, Maryam-Sadat; Ghadiri-Anari, Akram

2017-06-01

In recent years, metabolic syndrome, obesity, diabetes and cardiovascular disease has had a tremendous elevation growth. Many studies have demonstrated negative correlation between vitamin D deficiency and indexes of metabolic syndrome in obese patients. This study was designed to find the relation between vitamin D deficiency and markers of metabolic syndrome among overweight and obese adults referred to obesity center of Shahid Sadoughi hospital in 2014. Eighty-nine overweight and obese adults (79 women and 10 men), who 13 subjects were overweight and 76 subjects were obese were recruited in this cross-sectional study. Total cholesterol, high-density lipoprotein cholesterol, triglyceride, plasma glucose and vitamin D were measured. IDF criteria were used for identifying subjects with metabolic syndrome. Demographic questionnaire was completed. Statistical analysis was performed using SPSS version 16.0. Fisher exact test, logistic regression, and Spearman correlation coefficient were used. The frequency of vitamin D deficiency was 93.2%. According to IDF criteria, the frequency of metabolic syndrome was 36%. There was no significant relationship between vitamin D deficiency and metabolic syndrome. Among metabolic syndrome indicators, there was a significant direct relationship between vitamin D level with FBS (P=0.013) and SBP (P=0.023). There was no significant relationship between vitamin D deficiency and metabolic syndrome. Due to the lack of relationship between vitamin D deficiency and metabolic syndrome, small number of participants in this study and very low case of normal vitamin D level, further studies are needed.

Arginase-1 deficiency.

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Sin, Yuan Yan; Baron, Garrett; Schulze, Andreas; Funk, Colin D

2015-12-01

Arginase-1 (ARG1) deficiency is a rare autosomal recessive disorder that affects the liver-based urea cycle, leading to impaired ureagenesis. This genetic disorder is caused by 40+ mutations found fairly uniformly spread throughout the ARG1 gene, resulting in partial or complete loss of enzyme function, which catalyzes the hydrolysis of arginine to ornithine and urea. ARG1-deficient patients exhibit hyperargininemia with spastic paraparesis, progressive neurological and intellectual impairment, persistent growth retardation, and infrequent episodes of hyperammonemia, a clinical pattern that differs strikingly from other urea cycle disorders. This review briefly highlights the current understanding of the etiology and pathophysiology of ARG1 deficiency derived from clinical case reports and therapeutic strategies stretching over several decades and reports on several exciting new developments regarding the pathophysiology of the disorder using ARG1 global and inducible knockout mouse models. Gene transfer studies in these mice are revealing potential therapeutic options that can be exploited in the future. However, caution is advised in extrapolating results since the lethal disease phenotype in mice is much more severe than in humans indicating that the mouse models may not precisely recapitulate human disease etiology. Finally, some of the functions and implications of ARG1 in non-urea cycle activities are considered. Lingering questions and future areas to be addressed relating to the clinical manifestations of ARG1 deficiency in liver and brain are also presented. Hopefully, this review will spark invigorated research efforts that lead to treatments with better clinical outcomes.

Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene.

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Soto, Angela Ganan; McIntyre, Adam; Agrawal, Sungeeta; Bialo, Shara R; Hegele, Robert A; Boney, Charlotte M

2015-09-04

Lipoprotein Lipase (LPL) deficiency is a rare autosomal recessive disorder with a heterogeneous clinical presentation. Several mutations in the LPL gene have been identified to cause decreased activity of the enzyme. An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. Genomic DNA analysis identified lipoprotein lipase deficiency due to compound heterozygosity including a novel p.Q240H mutation in exon 5 of the lipoprotein lipase (LPL) gene. His severe hypertriglyceridemia, including xanthomas, resolved with dietary long-chain fat restriction. We describe a novel mutation of the LPL gene causing severe hypertriglyceridemia and report the response to treatment. A review of the current literature regarding LPL deficiency syndrome reveals a few potential new therapies under investigation.

Management of Iron Deficiency Anemia

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Jimenez, Kristine; Kulnigg-Dabsch, Stefanie

2015-01-01

Anemia affects one-fourth of the world’s population, and iron deficiency is the predominant cause. Anemia is associated with chronic fatigue, impaired cognitive function, and diminished well-being. Patients with iron deficiency anemia of unknown etiology are frequently referred to a gastroenterologist because in the majority of cases the condition has a gastrointestinal origin. Proper management improves quality of life, alleviates the symptoms of iron deficiency, and reduces the need for blood transfusions. Treatment options include oral and intravenous iron therapy; however, the efficacy of oral iron is limited in certain gastrointestinal conditions, such as inflammatory bowel disease, celiac disease, and autoimmune gastritis. This article provides a critical summary of the diagnosis and treatment of iron deficiency anemia. In addition, it includes a management algorithm that can help the clinician determine which patients are in need of further gastrointestinal evaluation. This facilitates the identification and treatment of the underlying condition and avoids the unnecessary use of invasive methods and their associated risks. PMID:27099596

Systematic review and meta-analysis on the prevalence of vitamin D deficiency in patients with chronic pancreatitis.

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Hoogenboom, S A; Lekkerkerker, S J; Fockens, P; Boermeester, M A; van Hooft, J E

2016-01-01

Patients with chronic pancreatitis (CP) are at risk of malnutrition due to malabsorption, pain and/or alcohol consumption. This can cause vitamin D insufficiency or deficiency, which is associated with osteoporosis and increased risks of fractures. We aimed to perform a meta-analysis to determine the prevalence of vitamin D insufficiency and deficiency in CP patients. Furthermore, we compared these results with healthy controls. We performed a systematic review and meta-analysis on the literature by searching PubMed and EMBASE (January 2000-December 2015) on CP and vitamin D. Primary outcome was prevalence of vitamin D insufficiency ( 0.05). There is a high prevalence of vitamin D insufficiency and deficiency in CP patients. Nevertheless, there is no significant difference in prevalence of vitamin D insufficiency and deficiency compared to healthy controls. Further research should indicate the clinical relevance and consequences of these findings for clinical practice. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Mechanistic Bases of Neurotoxicity Provoked by Fatty Acids Accumulating in MCAD and LCHAD Deficiencies

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Alexandre U. Amaral PhD

2017-03-01

Full Text Available Fatty acid oxidation defects (FAODs are inherited metabolic disorders caused by deficiency of specific enzyme activities or transport proteins involved in the mitochondrial catabolism of fatty acids. Medium-chain fatty acyl-CoA dehydrogenase (MCAD and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD deficiencies are relatively common FAOD biochemically characterized by tissue accumulation of medium-chain fatty acids and long-chain 3-hydroxy fatty acids and their carnitine derivatives, respectively. Patients with MCAD deficiency usually have episodic encephalopathic crises and liver biochemical alterations especially during crises of metabolic decompensation, whereas patients with LCHAD deficiency present severe hepatopathy, cardiomyopathy, and acute and/or progressive encephalopathy. Although neurological symptoms are common features, the underlying mechanisms responsible for the brain damage in these disorders are still under debate. In this context, energy deficiency due to defective fatty acid catabolism and hypoglycemia/hypoketonemia has been postulated to contribute to the pathophysiology of MCAD and LCHAD deficiencies. However, since energetic substrate supplementation is not able to reverse or prevent symptomatology in some patients, it is presumed that other pathogenetic mechanisms are implicated. Since worsening of clinical symptoms during crises is accompanied by significant increases in the concentrations of the accumulating fatty acids, it is conceivable that these compounds may be potentially neurotoxic. We will briefly summarize the current knowledge obtained from patients with these disorders, as well as from animal studies demonstrating deleterious effects of the major fatty acids accumulating in MCAD and LCHAD deficiencies, indicating that disruption of mitochondrial energy, redox, and calcium homeostasis is involved in the pathophysiology of the cerebral damage in these diseases. It is presumed that these findings based on the

Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency

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Caitriona McLean

2009-01-01

Full Text Available Caitriona McLean*, Catherine M Greene*, Noel G McElvaneyRespiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland; *Each of these authors contributed equally to this workAbstract: Alpha-1 antitrypsin (A1AT is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to <35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys. ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs and RNA interference (RNAi, which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.Keywords: alpha-1 antitrypsin deficiency, siRNA, peptide nucleic acid, ribozymes

Assessment of iron deficiency in pregnant women by determining iron status

International Nuclear Information System (INIS)

Raza, N.; Munazza, B.; Ayub, M.; Sarwar, I

2011-01-01

Background: Pregnant women constitute a high risk group for iron deficiency. Maternal iron deficiency and particularly iron deficiency anaemia may be associated with detrimental effects on maternal and infant function and particularly with a higher risk of preterm delivery and delivery of low birth weight neonates. Objective of this study was to assess and compare the iron status of normal healthy non-pregnant women with that of pregnant women of Hazara Division. Methods: This study was conducted at Faculty of Health Sciences, Hazara University, and Ayub Medical College, Abbottabad from first March to /31 August 2006. Altogether 120 women, 90 pregnant at various stages of pregnancy and 30 non-pregnant women as control group were included in this study by convenience sampling. Their iron status was assessed by determination of haemoglobin (Hb), Serum ferritin, Serum-iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), and Percentage saturation of transferrin. Data generated on these variables were subjected to ANOVA and correlation analysis. Results: The salient finding of this study is a significant decrease in Hb, Serum ferritin, Serum iron, percentage saturation of transferrin and a significant increase in values of TIBC and a pronounced increase in UIBC in second and third trimester compared to first trimester in iron deficient pregnant women. The mean values of Hb, SF, and Fe/TIBC% were significantly lower in the cases than in the control and significantly higher values of TIBC and UIBC were observed in the cases compared to controls. Significant correlations were observed for TIBC, UIBC and Fe/TIBC% against serum iron in different trimesters of pregnancy. Conclusion: A high percentage of the pregnant women are iron deficient due to factors such as high parity, poor dietary habits and socioeconomic status. (author)

Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism

DEFF Research Database (Denmark)

Petersen, Pia Steen; Jin, Chunyu; Madsen, Andreas Nygaard

2011-01-01

, conceivably due to decreased energy expenditure and adipocyte lipolytic activity.-Petersen, P. S., Jin, C., Madsen, A. N., Rasmussen, M., Kuhre, R., L. Egerod, K. L., Nielsen, L. B., Schwartz. T. W., Holst, B. Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism....

On the Ability To Infer Deficiency in Mathematics From Performance in Physics Using Hierarchies

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Riban, David M.

1971-01-01

Presents the procedures, results, and conclusions of a study designed to see if mathematical deficiencies can be inferred from PSSC students' performance by using a hierarchical model of requisite skills. Assuming inferences were possible, remediation was given. No effect due to remediation was observed but analysis indicated incidental learning…

Dopamine beta-hydroxylase deficiency

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Senard Jean-Michel

2006-03-01

Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

Biglycan deficiency increases osteoclast differentiation and activity due to defective osteoblasts

DEFF Research Database (Denmark)

Bi, Yanming; Nielsen, Karina L; Kilts, Tina M

2006-01-01

to be independent of the differential production of soluble RANKL and OPG and, instead, due to a decrease in osteoblast maturation accompanied by increase in osteoblastic proliferation. In addition to the imbalance between differentiation and proliferation, there was a differential decrease in secretory leukocyte......Bone mass is maintained by a fine balance between bone formation by osteoblasts and bone resorption by osteoclasts. Although osteoblasts and osteoclasts have different developmental origins, it is generally believed that the differentiation, function, and survival of osteoclasts are regulated...... by osteogenic cells. We have previously shown that the extracellular matrix protein, biglycan (Bgn), plays an important role in the differentiation of osteoblast precursors. In this paper, we showed that Bgn is involved in regulating osteoclast differentiation through its effect on osteoblasts...

Nicotinic acetylcholine receptors containing the α7-like subunit mediate contractions of muscles responsible for space positioning of the snail, Helix pomatia L. tentacle.

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Tibor Kiss

Full Text Available Three recently discovered tentacle muscles are crucial to perform patterned movements of upper tentacles of the terrestrial snail, Helix pomatia. The muscles receive central and peripheral excitatory cholinergic innervation lacking inhibitory innervation. Here, we investigate the pharmacology of acetylcholine (ACh responses in muscles to determine the properties of the ACh receptor (AChR, the functional availability of which was assessed using isotonic contraction measurement. Using broad spectrum of nicotinic and muscarinic ligands, we provide the evidence that contractions in the muscles are attributable to the activation of nAChRs that contain the α7-like subunit. Contractions could be evoked by nicotine, carbachol, succinylchloride, TMA, the selective α7-nAChR agonist choline chloride, 3-Bromocytisine and PNU-282987, and blocked by nAChR selective antagonists such as mytolon, hexamethonium, succinylchloride, d-tubocurarine, hemicholinium, DMDA (decamethonium, methyllycaconitine, α-Bungarotoxin (αBgTx and α-Conotoxin IMI. The specific muscarinic agonist oxotremorine and arecoline failed to elicit contractions. Based on these pharmacological properties we conclude that the Na+ and Ca2+ permeable AChRs of the flexor muscle are nicotinic receptors that contain the α7-like subunit. Immunodetection experiments confirmed the presence of α7- or α7-like AChRs in muscle cells, and α4-AChRs in nerves innervating the muscle. These results support the conclusion that the slowly desensitizing αBgTx-sensitive responses obtained from flexor muscles are produced by activation of α7- like AChRs. This is the first demonstration of postsynaptic expression and an obligatory role for a functional α7-like nAChR in the molluscan periphery.

Increased glucose dependence in resting, iron-deficient rats

International Nuclear Information System (INIS)

Brooks, G.A.; Henderson, S.A.; Dallman, P.R.

1987-01-01

Rates of blood glucose and lactate turnover were assessed in resting iron-deficient and iron-sufficient (control) rats to test the hypothesis that dependence on glucose metabolism is increased in iron deficiency. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient group) for 3-4 wk. The iron-deficient group became anemic, with hemoglobin levels of 6.4 ± 0.2 compared with 13.8 ± 0.3 g/dl for controls. Rats received a 90-min primed continuous infusion of D-[6- 3 H]glucose and sodium L-[U- 14 C]lactate via a jugular catheter. Serial samples were taken from a carotid catheter for concentration and specific activity determinations. Iron-deficient rats had significantly higher blood glucose and lactate concentrations than controls. The iron-deficient group had a significantly higher glucose turnover rate than the control group. Significantly more metabolite recycling in iron-deficient rats was indicated by greater incorporation of 14 C into blood glucose. Assuming a carbon crossover correction factor of 2, half of blood glucose arose from lactate in deficient animals. By comparison, only 25% of glucose arose from lactate in controls. Lack of a difference in lactate turnover rates between deficient rats and controls was attributed to 14 C recycling. The results indicate a greater dependence on glucose metabolism in iron-deficient rats

Neuropsychiatric manifestations of alkali metal deficiency and excess

Energy Technology Data Exchange (ETDEWEB)

Yung, C.Y.

1984-01-01

The alkali metals from the Group IA of the periodic table (lithium, sodium, potassium, rubidium, cesium and francium) are reviewed. The neuropsychiatric aspects of alkali metal deficiencies and excesses (intoxications) are described. Emphasis was placed on lithium due to its clinical uses. The signs and symptoms of these conditions are characterized by features of an organic brain syndrome with delirium and encephalopathy prevailing. There are no clinically distinctive features that could be reliably used for diagnoses. Sodium and potassium are two essential alkali metals in man. Lithium is used as therapeutic agent in bipolar affective disorders. Rubidium has been investigated for its antidepressant effect in a group of psychiatric disorders. Cesium is under laboratory investigation for its role in carcinogenesis and in depressive illness. Very little is known of francium due to its great instability for experimental study.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

Science.gov (United States)

Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

2016-01-01

Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Are MAO-A deficiency states in the general population and in putative high-risk populations highly uncommon?

Science.gov (United States)

Murphy, D L; Sims, K; Eisenhofer, G; Greenberg, B D; George, T; Berlin, F; Zametkin, A; Ernst, M; Breakefield, X O

1998-01-01

Lack of monoamine oxidase A (MAO-A) due to either Xp chromosomal deletions or alterations in the coding sequence of the gene for this enzyme are associated with marked changes in monoamine metabolism and appear to be associated with variable cognitive deficits and behavioral changes in humans and in transgenic mice. In mice, some of the most marked behavioral changes are ameliorated by pharmacologically-induced reductions in serotonin synthesis during early development, raising the question of possible therapeutic interventions in humans with MAO deficiency states. At the present time, only one multi-generational family and a few other individuals with marked MAO-A deficiency states have been identified and studied in detail. Although MAO deficiency states associated with Xp chromosomal deletions were identified by distinct symptoms (including blindness in infancy) produced by the contiguous Norrie disease gene, the primarily behavioral phenotype of individuals with the MAO mutation is less obvious. This paper reports a sequential research design and preliminary results from screening several hundred volunteers in the general population and from putative high-risk groups for possible MAO deficiency states. These preliminary results suggest that marked MAO deficiency states are very rare.

Atypical B12 Deficiency with Nonresolving Paraesthesia

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S. Haider

2013-01-01

Full Text Available Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS. This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of POEMS should be considered in patients with B12 deficiency unresponsive to therapy.

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency

NARCIS (Netherlands)

W.F. Blum (Werner); C.L. Deal (Cheri Lynn); A.G. Zimmermann (Alan); E.P. Shavrikova (Elena); C.J. Child (Christopher); C.A. Quigley (Charmian); S.L.S. Drop (Stenvert); G. Cutler (Gordon); R.G. Rosenfeld (Ron)

2014-01-01

textabstractObjective: We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD). Design: Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were

Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

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Biljana Musicki

Full Text Available Testosterone deficiency is associated with sickle cell disease (SCD, but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH levels compared with wild type (WT mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR, but not cholesterol side-chain cleavage enzyme (P450scc, in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

Reticulocyte maturity indices in iron deficiency anemia

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Muriel Wollmann

2014-01-01

Full Text Available Objective: The aim of this study was to analyze the reticulocyte maturity indices (low, medium, and high fluorescence ratios in iron deficient 1- to 6-year-old children, and identify the prevalence of iron deficiency anemia in this population. Methods: The present study included 39 subjects, divided into two groups: control subjects (n = 33, and subjects with iron deficiency anemia (n = 6. The results were analyzed by Student's t-test for comparison of means. Differences were considered significant when two-tailed p-value < 0.05. Results: Subjects with iron deficiency anemia presented increases in the proportion of mean (10.3 ± 4.7% vs. 6.0 ± 3.4%; p-value = 0.003, and high fluorescence reticulocytes (2.3 ± 0.87% vs. 0.9 ± 0.9%; p-value = 0.03 compared to the control group. The prevalence of anemia in this population was 15% (n = 6. Conclusion: The indices related to immaturity of reticulocytes are higher in the presence of iron deficiency, thus demonstrating a deficiency in the raw material to form hemoglobin and are, therefore, possible early markers of iron deficiency and anemia. We emphasize the need to standardize these indices for use in clinical practice and lab test results.

DNA-based prenatal diagnosis for severe and variant forms of multiple acyl-CoA dehydrogenation deficiency

DEFF Research Database (Denmark)

Olsen, Rikke K J; Andresen, Brage S; Christensen, Ernst

2005-01-01

OBJECTIVES: Multiple acyl-CoA dehydrogenation deficiency (MADD) is a clinically heterogeneous disorder of mitochondrial fatty acid, amino acid, and choline oxidation due to mutations in the genes encoding electron transfer flavoprotein (ETF) or ETF ubiquinone oxidoreductase (ETFQO). So far...

Radio-sensitization of WRN helicase deficient cancer cells by targeting homologous recombination pathway

International Nuclear Information System (INIS)

Gupta, Pooja; Saha, Bhaskar; Patro, Birija Sankar; Chattopadhyay, Subrata

2016-01-01

Ionizing radiation (IR) induced DNA double-strand breaks (DSBs) are primarily repaired by non-homologous end joining (NHEJ). However, it is well established that a subset DSBs which are accumulated in IR-induced G2 phase are dependent on homologous recombination (HR). DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyperdependent on DNA damage response pathways, including the CHK1-kinase-mediated HR-repair. These observations suggest that DNA repair deficient tumors should exhibit increased radio-sensitivity under HR inhibition. Genetic defects leading to functional loss of werner (WRN) protein is associated with genomic instability and increased cancer incidence. WRN function is known to be abrogated in several human cancer cells due to hypermethylation of CpGisland-promoter and transcriptional silencing of WRN gene. In the current investigation, using isogenic pairs of cell lines differing only in the WRN function, we showed that WRN-deficient cell lines were hyper-radiosensitive to CHK1 pharmacologic inhibition. Here, we found that unrepaired DSB was drastically increased in WRN-deficient cells vis-à-vis WRN-proficient cells in response to IR and CHK1 inhibitor (CHK1i). Our results revealed a marginal role of NHEJ pathway accountable for the radio-sensitivity of WRN-deficient cells. Interestingly, silencing CTIP, a HR protein required for RAD51 loading, significantly abrogated the CHK1i-mediated radiosensitivity in WRN-deficient cells. Silencing of WRN or CTIP individually led to no significant difference in the extent of DNA end resection, as required during HR pathway. Imperatively, our results revealed that WRN and CTIP together play a complementary role in executing DNA end resection during HR-mediated repair of IR induced DSBs. Altogether, our data indicated that inhibition of IR-induced HR pathway at RAD51 loading, but not at DSB end resection, make the WRN-deficient cancer cells

Diagnosis of thalassemia and iron deficiency anemia using confocal and atomic force microscopy

Science.gov (United States)

Tariq, Saira; Bilal, Muhammad; Shahzad, Shaheen; Firdous, Shamaraz; Aziz, Uzma; Ahmed, Mushtaq

2017-11-01

Anemia is the most prevalent blood disorder, categorized into thalassemia and iron deficiency anemia. In anemia, the morphology of erythrocytes is disturbed, thus leading to abnormal functioning of the erythrocytes. Globally, thalassemia affects 1.3% of individuals and is one of the most widespread monogenic disorders in Pakistan. All over the World, women and children are most frequently affected by a type of nutritional deficiency known as iron deficiency anemia. The morphological changes that occur in erythrocytes due to these diseases are investigated in this study at the nano-scale level. Fifty samples of blood from individuals suffering from thalassemia or iron deficiency anemia were obtained from different hospitals in Rawalpindi and Islamabad. The blood samples were scanned using atomic force microscopy (AFM) and laser scanning confocal microscopy (LSCM) to check the morphological changes in both types of anemia. According to the present study, thalassemia is most prevalent in females in the age group between 5 and 15 years old, and iron deficiency is most prevalent in females in the age groups of 16-25 and 36-45 years old. Erythrocyte morphology is the significant determinant for diagnosing and discriminating between these two types of diseases. The study reports deformed erythrocytes in anemic patients, which were different from the ones that existed in the control. Thalassemia erythrocytes showed a crenated shape, iron deficiency anemia erythrocytes showed an elliptocyte shape and healthy erythrocytes showed a biconcave disk shape when using AFM and LSCM. These techniques seem to be very promising, cheap and less time consuming in determining the structure-function relationship of erythrocytes of thalassemic and iron deficiency anemic patients. The results of LSCM and AFM are quite useful in determining the morphological changes in erythrocytes and to study the disease at the molecular level within short period of time. Hence, we encourage employing

[Use of copper oxide wire particles (Copinox) for the prevention of congenital copper deficiency in a herd of German Improved Fawn breed of goat].

Science.gov (United States)

Winter, P; Hochsteiner, W; Chizzola, R

2004-10-01

In a herd of German Improved Fawn breed of goat in the year 2000 neonatal kid losses due to congenital copper deficiencies were observed. To clarify the problems and to prevent losses in the next breeding season serum copper levels of 10 dams and four control Boer goats were investigated at four time points during one year. Additionally ten kids of the following year were sampled and the serum copper levels were studied. Immediatly after parturition and 8 weeks later the dams showed low serum copper levels (10.4 +/- 11.1 micromol/l, 5.7 +/- 2.9 micromol/l resp.). At the end of the pasture season an increase of serum copper could be measured (19.3 +/- 16.0 micromol/l). To prevent enzootic ataxia due to congenital copper deficiency, the dams were treated with copper oxide wire particles in the next late gestation. At this time point serum copper concentrations started to decrease (18.5 +/- 8.4 micromol/l). The re-examination 3 month later demonstrated an increase of the serum mean copper concentrations up to 23.4 micromol/l in the dams and to 16.2 micromol/l in the kids. The serum copper levels were significantly higher compared to the levels the year before. Big variation of the serum copper levels in the control Boer goats occurred during the year, but no clinical symptoms of copper deficiency could be observed. The copper levels in the grass and soil samples were 6.8 mg/kg and 0.2 mg/kg dry substance, respectively. A secondary copper deficiency based on cadmium could be excluded through the low levels of soil samples. The contents of sulphur and molybdenum were not determined. The results indicate that the German Improved Fawn breed of goats suffered from a primary copper deficiency due to the inefficient mineral supplementation. The administration of Copinox in the last third of the gestation leads to a continious raising of the copper concentrations in the serum and is suited to prevent ataxia due to congential copper deficiency in neonatal kids.

Japanese family with congenital factor VII deficiency.

Science.gov (United States)

Sakakibara, Kanae; Okayama, Yoshiki; Fukushima, Kenji; Kaji, Shunsaku; Muraoka, Michiko; Arao, Yujiro; Shimada, Akira

2015-10-01

Congenital factor VII (FVII) deficiency is a rare bleeding disorder with autosomal recessive inheritance. The present female patient was diagnosed with congenital FVII deficiency because of low hepaplastin test (HPT), although vitamin K was given. Heterozygous p.A191T mutation was detected in the peripheral blood, and the same mutation was also found in the mother and sister. To the best of our knowledge, this is the fourth reported case of p.A191T mutation of FVII in the literature and the first to be reported in Japan. FVII coagulation activity (FVII:C) in asymptomatic heterozygous carriers is mildly reduced. Therefore, some patients may not be accurately diagnosed with congenital FVII deficiency. In infants with low HPT without vitamin K deficiency, congenital FVII deficiency should be considered. © 2015 Japan Pediatric Society.

Behavioral impairments in animal models for zinc deficiency

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Simone eHagmeyer

2015-01-01

Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

Carbohydrate metabolism in erythrocytes of copper deficient rats.

Science.gov (United States)

Brooks, S P J; Cockell, K A; Dawson, B A; Ratnayake, W M N; Lampi, B J; Belonje, B; Black, D B; Plouffe, L J

2003-11-01

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using (13)C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD(+). Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.

Sleep transitions in hypocretin-deficient narcolepsy.

Science.gov (United States)

Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

2013-08-01

Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype. We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients. Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001). In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches.

Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

Science.gov (United States)

... 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency ... of this enzyme. Because fluoropyrimidine drugs are also broken down by the dihydropyrimidine dehydrogenase enzyme, deficiency of ...

Screening for C3 deficiency in newborns using microarrays.

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Magdalena Janzi

Full Text Available BACKGROUND: Dried blood spot samples (DBSS from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.

Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents

DEFF Research Database (Denmark)

Bodo, Sahra; Colas, Chrystelle; Buhard, Olivier

2015-01-01

BACKGROUND & AIMS: Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas...... or leukemias, and brain tumors. There is no satisfactory method for diagnosis of CMMRD because screens for mutations in MMR genes are noninformative for 30% of patients. MMR-deficient cancer cells are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of errors...

LACTASE DEFICIENCY IN BABIES AND INFANTS

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E.A. Kornienko

2006-01-01

Full Text Available Lactose, the constituent disaccharide of milk and other dairy products, is an important nutrient in early childhood. Lactase breaks down lactose in small intestine. In most people the activity of lactase reduces with age. In infancy lactase deficiency tends to be either transient, which is more often, or secondary to intestinal diseases. Abdominal cramps, anxiety and dyspepsia are the common symptoms of lactase deficiency. Tactics of treatment should take into account a cause and severity of the condition. A specialized milk formula «enfamil lactofree», distinguished for its' optimal formulation, high clinical effectiveness and good tolerance, could be recommended for use in children with primary, transient and secondary lactase deficiency who receive formula and mixed feeding.Key words: lactose, lactase deficiency, lactose-free formula.

Genetics Home Reference: iron-refractory iron deficiency anemia

Science.gov (United States)

... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities.

Science.gov (United States)

Katayama, K; Yamada, K; Ornthanalai, V G; Inoue, T; Ota, M; Murphy, N P; Aruga, J

2010-02-01

Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

Decreased autophosphorylation of EGF receptor in insulin-deficient diabetic rats

International Nuclear Information System (INIS)

Okamoto, M.; Kahn, C.R.; Maron, R.; White, M.F.

1988-01-01

The authors have previously reported that despite an increase in receptor concentration, there is a decrease in autophosphorylation and tyrosine kinase activity of the insulin receptor in insulin-deficient diabetic rats. To determine if other tyrosine kinases might be altered, they have studied the epidermal growth factor (EGF) receptor kinase in wheat germ agglutinin-purified, Triton X-100-solubilized liver membranes from streptozotocin (STZ)-induced diabetic rats and the insulin-deficient BB rat. They find that autophosphorylation of EGF receptor is decreased in proportion to the severity of the diabetic state in STZ rats with a maximal decrease of 67%. A similar decrease in autophosphorylation was observed in diabetic BB rats that was partially normalized by insulin treatment. Separation of tryptic phosphopeptides by reverse-phase high-performance liquid chromatography revealed a decrease in labeling at all sites of autophosphorylation. A parallel decrease in EGF receptor phosphorylation was also found by immunoblotting with an antiphosphotyrosine antibody. EGF receptor concentration, determined by Scatchard analysis of 125 I-labeled EGF binding, was decreased by 39% in the STZ rat and 27% in the diabetic BB rat. Thus autophosphorylation of EGF receptor, like that of the insulin receptor, is decreased in insulin-deficient rat liver. In the case of EGF receptor, this is due in part to a decrease in receptor number and in part to a decrease in the specific activity of the kinase

The triad of Iron deficiency anemia, hepatosplenomegaly and ...

African Journals Online (AJOL)

2014-12-04

Dec 4, 2014 ... In conclusion, iron deficiency anemia occurring in the triad without zinc deficiency as .... a negative zinc balance and mask existing zinc deficiency.[10] ... erythropoiesis‑stimulating agents in men with chronic kidney disease.

Iron Deficiency Anaemia In Reproductive Age Women Attending ...

African Journals Online (AJOL)

Iron Deficiency Anaemia In Reproductive Age Women Attending Obstetrics And ... prevalence of iron deficiency anemia in reproductive age women, and their relation to ... Thus iron deficiency anemia during pregnancy in well-educated set up ...

Genetics Home Reference: 21-hydroxylase deficiency

Science.gov (United States)

... adrenal hyperplasias that impair hormone production and disrupt sexual development. 21-hydroxylase deficiency is responsible for about 95 ... excess production of androgens leads to abnormalities of sexual development in people with 21-hydroxylase deficiency . A lack ...

Genetics Home Reference: ataxia with vitamin E deficiency

Science.gov (United States)

... Conditions Ataxia with vitamin E deficiency Ataxia with vitamin E deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Ataxia with vitamin E deficiency is a disorder that impairs the body's ...

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype.

Science.gov (United States)

Relling, M V; McDonagh, E M; Chang, T; Caudle, K E; McLeod, H L; Haidar, C E; Klein, T; Luzzatto, L

2014-08-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD-deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use. The purpose of this article is to help interpret the results of clinical G6PD genotype tests so that they can guide the use of rasburicase. Detailed guidelines on other aspects of the use of rasburicase, including analyses of cost-effectiveness, are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on https://www.pharmgkb.org/page/cpic to reflect new developments in the field.

Maternal supplementation for prevention and treatment of vitamin D deficiency in exclusively breastfed infants.

Science.gov (United States)

Haggerty, Linda L

2011-06-01

Current research links newborn and infant vitamin D deficiency with various clinical outcomes, including rickets, failure to thrive, type 1 diabetes, and other immune-related diseases. Breastfed infants are often at a greater risk of developing deficiency due to their mothers' low vitamin D status. Human milk reflects the vitamin D status of the mother and often contains inadequate levels of 25-hydroxyvitamin D for infant nutrition. In 2008 the American Academy of Pediatrics (AAP) recommended 400 IU of vitamin D supplementation of all infants. However, research has indicated low levels of compliance of vitamin D supplementation of breastfed infants and a high incidence of vitamin D deficiency in the United States. Many breastfeeding advocates believe that the AAP's recommendations undermine breastfeeding, implying that human milk is inadequate for infant nutrition. Lactating mothers are also reluctant to add any supplements to their breastmilk. The literature review will examine the effectiveness and safety of maternal vitamin D supplementation for prevention and/or treatment of vitamin D deficiency in breastfed infants and lactating mothers. This method of prevention and intervention provides pediatric providers and certified lactation consultants with an alternative approach for education, counseling, promotion of breastfeeding, and treatment to improve maternal and infant health.

Malaria infectivity of xanthurenic acid-deficient anopheline mosquitoes produced by TALEN-mediated targeted mutagenesis.

Science.gov (United States)

Yamamoto, Daisuke S; Sumitani, Megumi; Hatakeyama, Masatsugu; Matsuoka, Hiroyuki

2018-02-01

Anopheline mosquitoes are major vectors of malaria parasites. When the gametocytes of the malaria parasite are transferred from a vertebrate to mosquitoes, they differentiate into gametes, and are fertilized in the midguts of mosquitoes. Xanthurenic acid (XA), a waste product of the ommochrome synthesis pathway, has been shown to induce exflagellation during microgametogenesis in vitro; however, it currently remains unclear whether endogenous XA affects the infectivity of anopheline mosquitoes to malaria parasites in vivo due to the lack of appropriate experimental systems such as a XA-deficient line. In the present study, we produced a XA-deficient line in Anopheles stephensi using transcription activator-like effector nuclease (TALEN)-mediated gene targeting (knockout) of the kynurenine 3-monooxygenase (kmo) gene, which encodes an enzyme that participates in the ommochrome synthesis pathway. The knockout of kmo resulted in the absence of XA, and oocyst formation was inhibited in the midguts of these XA-deficient mosquitoes, which, in turn, reduced sporozoite numbers in their salivary glands. These results suggest that endogenous XA stimulates exflagellation, and enhances the infectivity of anopheline mosquitoes to malaria parasites in vivo. The XA-deficient line of the anopheline mosquito provides a useful system for analyzing and understanding the associated factors of malaria gametogenesis in the mosquito midgut.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats

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Viridiana Alcántara-Alonso

2017-10-01

Full Text Available Individuals who consume a diet deficient in zinc (Zn-deficient develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH concentration, but unchanged thyroid hormone (TH levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII in the medial-basal hypothalamus (MBH. PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH. This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

OpenAIRE

Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.

2012-01-01

Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostruc...

DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

OpenAIRE

Poulogiannis , George; Frayling , Ian; Arends , Mark

2009-01-01

Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

Vitamin D deficiency presenting with cardiogenic shock in an infant

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Manish Kumar

2011-01-01

Full Text Available A 2-month-old child was referred as a case of dilated cardiomyopathy with cardiogenic shock. On evaluation, hypocalcemia secondary to severe vitamin D deficiency was found. There were no clinical or radiological features of rickets. The child had developed multiorgan failure due to cardiogenic shock at the time of admission and could not be saved despite adequate ventilatory and pharmacologic support. Hypocalcemia should be considered as an important differential diagnosis in cases of dilated cardiomyopathy in infants.

Iodine deficiency and thyroid disorders.

Science.gov (United States)

Zimmermann, Michael B; Boelaert, Kristien

2015-04-01

Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency.

Science.gov (United States)

Frisén, Louise; Nordenström, Anna; Falhammar, Henrik; Filipsson, Helena; Holmdahl, Gundela; Janson, Per Olof; Thorén, Marja; Hagenfeldt, Kerstin; Möller, Anders; Nordenskjöld, Agneta

2009-09-01

Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.

Zinc Deficiency in Latin America and the Caribbean.

Science.gov (United States)

Cediel, Gustavo; Olivares, Manuel; Brito, Alex; Cori, Héctor; López de Romaña, Daniel

2015-06-01

Zinc deficiency affects multiple vital functions in the life cycle, especially growth. Limited information is available on the magnitude of zinc deficiency in Latin America and the Caribbean. To examine the latest available information on both the prevalence of zinc deficiency and the risk of zinc deficiency in Latin America and the Caribbean. The prevalence of zinc deficiency was identified through a systematic review looking for the latest available data on serum zinc concentrations from surveys or studies with national representativeness conducted in Latin America and the Caribbean. The risk of zinc deficiency in Latin America and the Caribbean was estimated based on dietary zinc inadequacy (according to the 2011 National Food Balance Sheets) and stunting in children under 5 years of age. Only four countries had available national biochemical data. Mexican, Colombian, Ecuadorian, and Guatemalan children under 6 years of age and women 12 to 49 years of age had a high prevalence of zinc deficiency (19.1% to 56.3%). The countries with the highest risk of zinc deficiency (estimated prevalence of inadequate zinc intake > 25% plus prevalence of stunting > 20%) were Belize, Bolivia, El Salvador, Guatemala, Haiti, Honduras, Nicaragua, and Saint Vincent and the Grenadines. Zinc dietary inadequacy was directly correlated with stunting (r = 0.64, p zinc deficiency in children under 6 years of age and women 12 to 49 years of age. High rates of both estimated zinc dietary inadequacy and stunting were also reported in most Latin America and Caribbean countries.

Mutations and phenotype in isolated glycerol kinase deficiency

Energy Technology Data Exchange (ETDEWEB)

Walker, A.P.; Muscatelli, F.; Stafford, A.N.; Monaco, A.P. [Inst. of Molecular Medicine, Oxford (United Kingdom)] [and others

1996-06-01

We demonstrate that isolated glycerol kinase (GK) deficiency in three families results from mutation of the Xp21 GK gene. GK mutations were detected in four patients with widely differing phenotypes. Patient 1 had a splice-site mutation causing premature termination. His general health was good despite absent GK activity, indicating that isolated GK deficiency can be silent. Patient 2 had GK deficiency and a severe phenotype involving psychomotor retardation and growth delay, bone dysplasia, and seizures, similar to the severe phenotype of one of the first described cases of GK deficiency. His younger brother, patient 3, also had GK deficiency, but so far his development has been normal. GK exon 17 was deleted in both brothers, implicating additional factors in causation of the severe phenotype of patient 2. Patient 4 had both GK deficiency with mental retardation and a GK missense mutation (D440V). Possible explanations for the phenotypic variation of these four patients include ascertainment bias; metabolic or environmental stress as a precipitating factor in revealing GK-related changes, as has previously been described in juvenile GK deficiency; and interactions with functional polymorphisms in other genes that alter the effect of GK deficiency on normal development. 36 refs., 4 figs., 1 tab.

Thyroid disorders in mild iodine deficiency

DEFF Research Database (Denmark)

Laurberg, P; Nøhr, S B; Pedersen, K M

2000-01-01

Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism...... endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine...... deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency...

Iron deficiency anemia from diagnosis to treatment in children

OpenAIRE

Özdemir, Nihal

2015-01-01

Iron deficiency is the most common nutritional deficiency worldwide and an important public health problem especially in developing countries. Since the most important indicator of iron deficieny is anemia, the terms “iron deficiency” and “iron deficiency anemia” are often used interchangeably. However, iron deficiency may develop in the absence of anemia and the tissues may be affected from this condition. The most common causes of iron deficiency in children include insufficient intake toge...

Cobalamin deficiency, hyperhomocysteinemia, and dementia

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Steven F Werder

2010-04-01

Full Text Available Steven F Werder1,21Kansas University School of Medicine – Wichita, Wichita, KS, USA; 2Community Health Center of Southeast Kansas, Pittsburg, KS, USAIntroduction: Although consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1 Which patients should be tested? (2 What test should be ordered? (3 How are inferences made from such testing? (4 In addition to serum B12, should other tests be ordered? (5 Is B12 deficiency compatible with dementia of the Alzheimer’s type? (6 What is to be expected from treatment? (7 How is B12 deficiency treated?Methods: On January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hyperhomocysteinemia, and dementia. After limiting the search terms, all abstracts and/or articles and other references were categorized into six major groups (general, biochemistry, manifestations, associations and risks, evaluation, and treatment and then reviewed in answering the above questions.Results: The six major groups above are described in detail. Seventy-five key studies, series, and clinical trials were identified. Evidence-based suggestions for patient management were developed.Discussion: Evidence is convincing that hyperhomocysteinemia, with or without hypovitaminosis B12, is a risk factor for dementia. In the absence of hyperhomocysteinemia, evidence is less convincing that hypovitaminosis B12 is a risk factor for dementia. B12 deficiency manifestations are variable and include abnormal psychiatric, neurological, gastrointestinal, and hematological findings. Radiological images of individuals with hyperhomocysteinemia frequently demonstrate leukoaraiosis. Assessing serum B12 and treatment of B12 deficiency is crucial for those cases in which pernicious anemia is suspected and may be useful for mild cognitive impairment and mild to moderate dementia. The serum B12 level is the standard initial test

2-Methylbutyryl-coenzyme A dehydrogenase deficiency

DEFF Research Database (Denmark)

Sass, Jörn Oliver; Ensenauer, Regina; Röschinger, Wulf

2008-01-01

2-Methylbutyryl-CoA dehydrogenase (MBD; coded by the ACADSB gene) catalyzes the step in isoleucine metabolism that corresponds to the isovaleryl-CoA dehydrogenase reaction in the degradation of leucine. Deficiencies of both enzymes may be detected by expanded neonatal screening with tandem...... individuals showed clinical symptoms attributable to MBD deficiency although the defect in isoleucine catabolism was demonstrated both in vivo and in vitro. Several mutations in the ACADSB gene were identified, including a novel one. MBD deficiency may be a harmless metabolic variant although significant...

Iron-Deficiency Anemia

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Full Text Available ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

Expression of five acetylcholine receptor subunit genes in Brugia malayi adult worms

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Ben-Wen Li

2015-12-01

Full Text Available Acetylcholine receptors (AChRs are required for body movement in parasitic nematodes and are targets of “classical” anthelmintic drugs such as levamisole and pyrantel and of newer drugs such as tribendimidine and derquantel. While neurotransmission explains the effects of these drugs on nematode movement, their effects on parasite reproduction are unexplained. The levamisole AChR type (L-AChRs in Caenorhabditis elegans is comprised of five subunits: Cel-UNC-29, Cel-UNC-38, Cel-UNC-63, Cel-LEV-1 and Cel-LEV-8. The genome of the filarial parasite Brugia malayi contains nine AChRs subunits including orthologues of Cel-unc-29, Cel-unc-38, and Cel-unc-63. We performed in situ hybridization with RNA probes to localize the expression of five AChR genes (Bm1_35890-Bma-unc-29, Bm1_20330-Bma-unc-38, Bm1_38195-Bma-unc-63, Bm1_48815-Bma-acr-26 and Bm1_40515-Bma-acr-12 in B. malayi adult worms. Four of these genes had similar expression patterns with signals in body muscle, developing embryos, spermatogonia, uterine wall adjacent to stretched microfilariae, wall of Vas deferens, and lateral cord. Three L-AChR subunit genes (Bma-unc-29, Bma-unc-38 and Bma-unc-63 were expressed in body muscle, which is a known target of levamisole. Bma-acr-12 was co-expressed with these levamisole subunit genes in muscle, and this suggests that its protein product may form receptors with other alpha subunits. Bma-acr-26 was expressed in male muscle but not in female muscle. Strong expression signals of these genes in early embryos and gametes in uterus and testis suggest that AChRs may have a role in nervous system development of embryogenesis and spermatogenesis. This would be consistent with embryotoxic effects of drugs that target these receptors in filarial worms. Our data show that the expression of these receptor genes is tightly regulated with regard to localization in adult worms and developmental stage in embryos and gametes. These results may help to explain the

Physiological, Ultrastructural and Proteomic Responses in the Leaf of Maize Seedlings to Polyethylene Glycol-Stimulated Severe Water Deficiency

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Ruixin Shao

2015-09-01

Full Text Available After maize seedlings grown in full-strength Hoagland solution for 20 days were exposed to 20% polyethylene glycol (PEG-stimulated water deficiency for two days, plant height, shoot fresh and dry weights, and pigment contents significantly decreased, whereas malondialdehyde (MDA content greatly increased. Using transmission electron microscopy, we observed that chloroplasts of mesophyll cells in PEG-treated maize seedlings were swollen, with a disintegrating envelope and disrupted grana thylakoid lamellae. Using two-dimensional gel electrophoresis (2-DE method, we were able to identify 22 protein spots with significantly altered abundance in the leaves of treated seedlings in response to water deficiency, 16 of which were successfully identified. These protein species were functionally classified into signal transduction, stress defense, carbohydrate metabolism, protein metabolism, and unknown categories. The change in the abundance of the identified protein species may be closely related to the phenotypic and physiological changes due to PEG-stimulated water deficiency. Most of the identified protein species were putatively located in chloroplasts, indicating that chloroplasts may be prone to damage by PEG stimulated-water deficiency in maize seedlings. Our results help clarify the molecular mechanisms of the responses of higher plants to severe water deficiency.

Living with transversal upper limb reduction deficiency : Limitations experienced by young adults during their transition to adulthood

NARCIS (Netherlands)

Lankhorst, Ilse M. F.; Baars, Erwin C. T.; van Wijk, Iris; Janssen, Wim G. M.; Poelma, Margriet J.; van der Sluis, Corry K.

2017-01-01

Introduction: During transition to adulthood young adults with disabilities are at risk of experiencing limitations due to changing physical and social requirements. Purpose: To determine whether young adults with transversal upper limb reduction deficiency (tULRD) have experienced limitations in

Glutamine 57 at the complementary binding site face is a key determinant of morantel selectivity for {alpha}7 nicotinic receptors.

Science.gov (United States)

Bartos, Mariana; Price, Kerry L; Lummis, Sarah C R; Bouzat, Cecilia

2009-08-07

Nicotinic receptors (AChRs) play key roles in synaptic transmission. We explored activation of neuronal alpha7 and mammalian muscle AChRs by morantel and oxantel. Our results revealed a novel action of morantel as a high efficacy and more potent agonist than ACh of alpha7 receptors. The EC(50) for activation by morantel of both alpha7 and alpha7-5HT(3A) receptors is 7-fold lower than that determined for ACh. The minimum morantel concentration required to activate alpha7-5HT(3A) channels is 6-fold lower than that of ACh, and activation episodes are more prolonged than in the presence of ACh. By contrast, oxantel is a weak agonist of alpha7 and alpha7-5HT(3A), and both drugs are very low efficacy agonists of muscle AChRs. The replacement of Gln(57) in alpha7 by glycine, which is found in the equivalent position of the muscle AChR, decreases the efficacy for activation and turns morantel into a partial agonist. The reverse mutation in the muscle AChR (epsilonG57Q) increases 7-fold the efficacy of morantel. The mutations do not affect activation by ACh or oxantel, indicating that this position is selective for morantel. In silico studies show that the tetrahydropyrimidinyl group, common to both drugs, is close to Trp(149) of the principal face of the binding site, whereas the other cyclic group is proximal to Gln(57) of the complementary face in morantel but not in oxantel. Thus, position 57 at the complementary face is a key determinant of the high selectivity of morantel for alpha7. These results provide new information for further progress in drug design.

An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

Science.gov (United States)

Hao, Shuangying; Li, Huihui; Sun, Xiaoyan; Li, Juan; Li, Kuanyu

2015-01-01

A case study of a female patient, diagnosed with iron deficiency anemia, was unresponsive to oral iron treatment and only partially responsive to parenteral iron therapy, a clinical profile resembling the iron-refractory iron deficiency anemia (IRIDA) disorder. However, the patient failed to exhibit microcytic phenotype, one of the IRIDA hallmarks. Biochemical assays revealed that serum iron, hepcidin, interluekin 6, and transferrin saturation were within the normal range of references or were comparable to her non-anemic offspring. Iron contents in serum and red blood cells and hemoglobin levels were measured, which confirmed the partial improvement of anemia after parenteral iron therapy. Strikingly, serum transferrin receptor in patient was almost undetectable, reflecting the very low activity of bone-marrow erythropoiesis. Our data demonstrate that this is not a case of systemic iron deficiency, but rather cellular iron deficit due to the low level of transferrin receptor, particularly in erythroid tissue.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... for gastrointestinal bleeding To see if gastrointestinal bleeding is causing your iron-deficiency anemia, your doctor may order the following procedures to guide treatment . Fecal ...

Iron-Deficiency Anemia