We present a case of a young female patient with fulminant hepatitis who showed an altered biodistribution of Ga-67, after being scanned twice at 10 month intevals. On initial scan, uptake of Ga-67 was increased in the liver, kidneys, and skeletons. Increased hepatic Ga-67 uptake may be explained by increased transferrin unbound Ga-67 that was taken up by the inflamed liver. The saturation of iron-binding proteins due to multiple transfusions may lead to increased renal and skeletal Ga-67 uptake. On follow-up scan hepatic Ga-67 uptake was markedly increased. Also increased Ga-67 uptake in the axial skeleton and normalized renal uptake were shown. The findings were consistent with iron deficiency anemia. This case demonstrates altered Ga-67 biodistribution associated with multiple transfusions, fulminant hepatitis, and iron deficiency anemia.
Anemia, Iron-Deficiency ; Female ; Follow-Up Studies ; Hepatitis ; Humans ; Iron-Binding Proteins ; Kidney ; Liver ; Skeleton ; Transferrin

Iron plays a key role in Parkinson s disease (PD). To illustrate the mechanism underlying the increase of iron in substantia nigra (SN) in PD, changes of the expression of divalent metal transporter 1 (DMT1) and iron content were examined in SN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice using immunohistochemistry and histochemistry respectively. Following MPTP treatment for 3 d, elevated iron staining was found in SN. A further increase in iron content was observed after 7 d. In these lesioned animals, tyrosine hydroxylase-immunoreactive DA neurons exhibited a decrease in number and morphological changes as well. There were two isoforms of DMT1 expressed in SN of mice. After MPTP treatment, the expression of DMT1 without IRE form increased in either group, whereas DMT1 with IRE form increased only after 7 d of MPTP treatment. These observations suggest that DMT1 is possibly involved in the process of iron accumulation in SN of MPTP-treated mice, which might be responsible for the subsequent death of DA neurons.
Animals ; Cation Transport Proteins ; metabolism ; Dopamine ; metabolism ; Iron ; metabolism ; Iron-Binding Proteins ; metabolism ; Mice ; Mice, Inbred C57BL ; Parkinsonian Disorders ; metabolism ; Protein Isoforms ; metabolism ; Substantia Nigra ; metabolism ; Transferrin ; metabolism

O1igodendrocytes are known to be responsible for the synthesis and maintenance of myelin sheath in the central nervous system, and their functional disturbance leads to defect in myelination. But, the fine mechanism of myelination by oligodendrocytes is not yet known, and iron metabolism in central nervous system is suspected to be related with myelination process by oligodendrocytes. Carbonic anhydrase-II[CA-II], transfe-rrin, and ferritin are known to be present at oligodendrocytes and suspected to play a role in iron metabolism of central nervous system. In this study, demyelination and remyelination of ICR mouse brains were induced using cuprizone, the copper-chelating agent, and immunohistochemical changes of CA-II-, transferrin-, and ferritin-immunoreactive oligodendrocytes at corpus callosum were observed. During demyelination by cuprizone feeding, the numbers of CA-II- and transferrin-immunoreactive oligodendrocytes were decreased. Especially, the decrease ratio of CA-II-positive cells was great. In contrast, the number of ferritin-positive oligodendrocytes was increased during demyelination by cuprizone feeding. Cessation of cuprizone feeding leaded remyelination and the numbers of CA-II-, transferrin-, and ferritin-immunoreactive oligodendrocytes were returned to normal level. In conclusion, the derangement of iron metabolism in oligodendrocytes may be related to demyelination mechanism of central nervous system, and the CA-II is suspected to have an important role in iron metabolism of oligodenrocytes in relation to demyelination and remyelination induced with cuprizone.
Animals ; Brain ; Carbon* ; Central Nervous System ; Corpus Callosum ; Cuprizone* ; Demyelinating Diseases ; Ferritins ; Iron ; Iron-Binding Proteins* ; Metabolism ; Mice* ; Mice, Inbred ICR ; Myelin Sheath ; Oligodendroglia ; Transferrin

OBJECTIVETo investigate the expression of divalent metal transporter 1 (DMT1) mRNA in male Sprague-Dawley rat heart of different ages and the expression of DMT1 regulated by dietary iron.

METHODSReverse transcriptase (RT)-PCR and Western blot were used in this study.

RESULTS(1)Two isoforms of DMT1 mRNA [with and without iron-responsive element (IRE)] were both detected in rat heart, which were correlated with heart iron content. During development, both of two isoforms of DMT1 mRNA expression were the lowest at the age of PND 7, and increased at PND 21, 63 to 196. (2) After fed with a high iron diet or low iron diet for 6 weeks, the rats developed iron overload or iron deficiency respectively. No significant differences in DMT1 mRNA expression were detected among iron overload, iron deficiency and control rats. By using Western blot analysis, a 21% and 40% reduction in DMT1 protein non IRE form and IRE form respectively were found in iron overload rat (P<0.01, compared with control). Increases (26% approximate, equals 28%) in the levels of two isoforms of DMT1 protein were also observed in iron deficient rat (P<0.01, compared with control).

CONCLUSIONThe level of DMT1 mRNA expression in heart is age dependent;the two isoforms of DMT1 protein may be both regulated by iron on the posttranscriptional mechanism.

Age Factors ; Animals ; Cation Transport Proteins ; genetics ; Gene Expression Regulation, Developmental ; Iron ; deficiency ; Iron Overload ; metabolism ; Iron-Binding Proteins ; genetics ; Male ; Myocardium ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Response Elements

BACKGROUND: To determine the thyroid ultrasound findings in association with anti-TPO positivity among patients with diffuse goiter.
DESIGN AND METHODS: We performed a cross-sectional study on patients with diffuse goiter seen at Makati Medical Center out-patient Endocrine clinics from October 1, 2011 to October 1, 2012. Patients with anti-TPO (thyroid peroxidase) above 100 pmol/L were considered anti-TPO positive and below this level were considered negative. After excluding patients with other possible causes of thyroiditis, thyroid ultrasound of anti-TPO positive and anti-TPO negative patients were reviewed and compared based on size, echogenicity, echopattern and vascularity of the thyroid parenchyma.
RESULTS: In 94 patients who qualified for the study, 43.6% were anti-TPO positive. A higher proportion of anti-TPO positive was seen among females compared to males by almost twofold (49.7% vs 25%, p0.05). Stratified according to age group for female patients, anti-TPO positivity is relatively higher among 31-50 years old (51.1%, p =0.753). Among male, anti-TPO positivity is present in all 18-2 years old which is significantly higher compared to other age group (p <0.01). Based on thyroid ultrasound findings, those with positive anti-TPO has
larger thyroid size in all measurement parameters (p= 0.0053). Among anti-TPO positive patients, frequent ultrasound findings were: hypoechoic (79% vs. 21%, p 0.001); heterogenous parenchyma (71% vs. 29%, p 0.001) and increased vascularity (93% vs. 7%, p 0.001). Of note is the absence of homogenous prenchyma fnding among anti-TPO positive. All 23 (100%) patients who showed combined findings of hypoechoic, heterogenous parenchyma and increased vascularity were anti-TPO positive.
CONCLUSION: Thyroid ultrasound findings that are found frequently among anti-TPO positive are increased thyroid size, parenchyma that are hypoechoiec and heterogenous and increased vascularity. Homogenous echotexture was not seen among anti-TPO positive. The combined sonographic characteristics of hypoechoic, heterogenous pattern and increased vascularity are highly suggestive of presence of anti-TPO (100%).

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Tpo Protein, Human ; Iodide Peroxidase ; Iron-binding Proteins ; Autoantigens ; Thyroiditis ; Goiter

Metal binding proteins or metallo-proteins are important for the stability of the protein and also serve as co-factors in various functions like controlling metabolism, regulating signal transport, and metal homeostasis. In structural genomics, prediction of metal binding proteins help in the selection of suitable growth medium for overexpression’s studies and also help in obtaining the functional protein. Computational prediction using machine learning approach has been widely used in various fields of bioinformatics based on the fact all the information contains in amino acid sequence. In this study, random forest machine learning prediction systems were deployed with simplified amino acid for prediction of individual major metal ion binding sites like copper, calcium, cobalt, iron, magnesium, manganese, nickel, and zinc.
Amino Acid Sequence* ; Binding Sites* ; Calcium ; Carrier Proteins ; Cobalt ; Computational Biology ; Copper ; Forests* ; Genomics ; Homeostasis ; Iron ; Machine Learning ; Magnesium ; Manganese ; Metabolism ; Nickel ; Zinc

OBJECTIVETo identify thyroid peroxidase (TPO) gene mutations in 35 patients with congenital hypothyroidism.

METHODGenomic DNA was isolated from peripheral blood samples of 35 patients with congenital hypothyroidism. All of the 17 exons and flanking introns of TPO gene were amplified by PCR, then the PCR products were sequenced bi-directionally and were analyzed by restriction endonucleases.

RESULTOne patient had compound heterozygous mutations c.961A>G/c.2422delT, one was c.2268insT/c.1477G>A, and three was homozygous mutation c.2268insT. The TPO gene mutation c.961A>G [p. Thr321Ala] was one novel mutation.

CONCLUSIONHigh frequency mutation in TPO gene was detected in patients with congenital hypothyroidism.

Autoantigens ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; Congenital Hypothyroidism ; genetics ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Infant ; Iodide Peroxidase ; genetics ; Iron-Binding Proteins ; genetics ; Male ; Mutation

The elderly are a peculiar group in terms of health management, as they often present with non-specific complaints which are challenging to interpret and may not present with the usual clinical picture of a disease. Objective. The study aims to determine the prevalence of thyroid dysfunction among asymptomatic, elderly Filipinos seen at the Philippine General Hospital (PGH). Methodology. Subjects aged 60 years and older seeking out-patient medical consult for non-thyroidal illness at the PGH were recruited. Patients with known thyroid or pituitary disease, previous thyroid or pituitary surgery, intake of medications known to affect thyroid hormone levels and critical illness were excluded. Fasting blood sugar (FBS), lipid profile, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-thyroperoxidase (anti-TPO) levels were taken. Based on FT4 and TSH levels, subjects were classified as overt hypothyroid, subclinical hypothyroid, euthyroid, subclinical hyperthyroid, or overt hyperthyroid. Results. One hundred eighty subjects were recruited, of whom 152 (84%) were female. Hypertension was the most common comorbidity (58.33%), followed by diabetes (36.67%). One hundred sixty-two (90%) were euthyroid, 12 (6.7%) subclinical hypothyroid, 4 (2.22%) subclinical hyperthyroid, and two (1.11%) overtly hyperthyroid. No one was overtly hypothyroid. There was a trend toward increasing prevalence of diabetes, hypertension, low HDL, obesity and overall cardiovascular risk among those with subclinical hypothyroidism. Conclusion. Subclinical hypothyroidism was the most prevalent thyroid dysfunction among asymptomatic elderly included in the study.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Cardiovascular Diseases ; Diabetes Mellitus ; Hospitals, General ; Hypertension ; Hyperthyroidism ; Hypothyroidism ; Iodide Peroxidase ; Iron-binding Proteins ; Obesity ; Outpatients ; Pituitary Diseases ; Thyrotropin ; Thyroxine

OBJECTIVETo study relationships between serum ferritin and bone metabolism in patients with hip fragility fractures.

METHODSThis cross-sectional study included 76 postmenopausal women with hip fracture from Feburary 2011 to June 2012. The mean age of the women was (73 ± 10) years (range, 55-93 years) and the mean duration of menstruation was (22 ± 10)years (range, 5-50 years). Serum concentrations of ferritin, transferrin, alkaline phosphatase (ALP), amino-terminal extension peptide of type I collagen (P1NP), C-terminal telopeptides of type I collagen (β-CTX)and femoral and lumbar bone mineral density by dual-energy X-ray absorptiometry were measured. Bone metabolism was compared between normal and elevated ferritin groups with t-test, Pearson linear, partial correlation and multiple regression analysis examined associations between iron- and bone-related markers.

RESULTSSerum ferritin concentration raised to (230 ± 146)µg/L, transferrin concentration reduced to (1.89 ± 0.33)g/L. P1NP concentration raised to (61 ± 32) ng/L when the concentration of serum ALP and β-CTX were in the normal range. T-scores for bone mineral density in the femoral neck (-2.0 ± 1.1) and lumbar (-2.1 ± 1.2) were below the normal ranges(-1.0-1.0). The subjects were divided into two groups according to serum ferritin concentration, normal group(serum ferritin concentration ≤ 150 µg/L, n = 25) and elevated group(serum ferritin concentration > 150 µg/L, n = 51). Patients of elevated group had lower bone mineral density in femoral neck and lumbar than normal group(t = 3.13,2.89, P < 0.01), and higher P1NP, β-CTX concentration (t = -2.38, -3.59, P < 0.05) . In partial correlation analysis adjusted for confounders, serum ferritin concentration was correlated negatively with bone mineral density in both femoral neck and lumbar (r = -0.335,-0.295, P < 0.05), and positively with P1NP and β-CTX (r = 0.467,0.414, P < 0.05), but not correlated with ALP (r = 0.188, P > 0.05). Transferrin concentration tended to be correlated positively with bone mineral density in both femoral neck and lumbar (r = 0.444, 0.262, P < 0.05) and negatively with ALP, P1NP and β-CTX(r = -0.326,-0.285,-0.278, P < 0.05).

CONCLUSIONSIron overload has a high prevalence in postmenopausal women with fragility fracture. Increased iron stores, which might lead to bone loss and lower bone mineral density by enhancing the activity of bone turnover, could be an independent factor to take effects on bone metabolism on postmenopausal women.

Aged ; Aged, 80 and over ; Bone Density ; Bone Remodeling ; Collagen Type I ; blood ; Cross-Sectional Studies ; Female ; Hip Fractures ; metabolism ; Humans ; Iron Overload ; Iron-Binding Proteins ; metabolism ; Middle Aged ; Osteoporosis, Postmenopausal ; metabolism ; Postmenopause ; Retrospective Studies

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. FXN is a mitochondrial protein which plays an important role in the regulation of intracellular iron trafficking, biogenesis of iron-sulfur cluster and heme, and removal of reactive oxygen species. Our previous work showed that tissue-specific expression of FXN in cerebellum and heart generates two novel isoforms. In order to find the isoforms in mouse tissues, we tried to obtain a polyclonal antibody against mouse Fxn with high specificity and sensitivity. Thus, the recombinant plasmid pET24(+)-mFxn was constructed to express his-tagged Fxn in BL21 (DE3) cells. The expressed protein is a mature form with 130 amino acids (aa, 14.38 kDa) without the N-terminal signal peptide (77 aa), purified on Ni-NTA column and further dialyzed with Centrifugal Filtration Device. The polyclonal antibody against Fxn was produced by immunizing rabbits with highly purified protein. The collected antiserums were preliminarily purified by precipitation with (NH4)2SO4. Western blotting analysis and cell immunofluorescence showed that the obtained antibody was able to detect both purified and endogenous Fxn. It also worked well in immunoprecipitation with mouse tissues. This is the first time, to our knowledge, to report that mouse Fxn was used as immunogen to generate antibody with high specificity and sensitivity. This work provides a powerful tool for our further research on mouse Fxn isoforms.
Animals ; Antibodies ; immunology ; metabolism ; Antibody Specificity ; immunology ; Escherichia coli ; genetics ; metabolism ; Female ; Genetic Engineering ; methods ; Immunization ; Iron-Binding Proteins ; genetics ; immunology ; Mice ; Rabbits ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology