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Diamond-Blackfan anemia (DBA) is a rare disorder characterized by congenital pure red cell aplasia. Mutations in ribosomal protein S19 (RPS19) have been identified in 25% of DBA patients. More recently, mutations in other ribosomal protein genes, namely RPS7, RPS15, RPS24, RPS17, RPS27A, RPL35a, RPL36, RPL11, and RPL5, have also been found in patients with DBA. Approximately 30-40% of affected patients have various associated physical anomalies, mostly craniofacial and at the extremities, but also cardiac or urogenital malformations. Anomalies of the urogenital tract in DBA patients comprise changes in the kidney (dysplasia, agenesis, duplication, horseshoe kidney) and genitalia (hypospadias). To date, disorders of sex development (DSD) have only been described once in association with DBA. We report here four DBA patients who exhibited DSD. Keywords Diamond-Blackfan anemia * Disorders of Sex Development * Erythroblastopenia * Intersexual genitalia, Introduction Diamond-Blackfan anemia (DBA) [1, 2] is a rare congenital erythroblastopenia occurring at a frequency of 4-7 per 1,000,000 live births with equal sex ratio [3-7]. Recent data show that [...]

In ischemic congestive heart failure (CHF), anemia is associated with poor prognosis. Whether anemia develops in nonischemic CHF is uncertain. The hematopoietic inhibitors TNF-[alpha] and nitric oxide (NO) are activated in ischemic CHF. We examined whether mice with ischemic or nonischemic CHF develop anemia and whether TNF-[alpha] and NO are involved. We studied mice (n = 7-9 per group) with CHF either due to myocardial infarction (MI) or to overexpression of the [Ca.sup.2+]-binding protein calsequestrin (CSQ) or to induced cardiac disruption of the sarcoplasmic reticulum [Ca.sup.2+]-ATPase 2 gene (SERCA2 KO). Hematopoiesis was analyzed by colony formation of [CD34.sup.+] bone marrow cells. Hemoglobin concentration was 14.0 [+ or -] 0.4 g/dl (mean [+ or -] SD) in controls, while it was decreased to 10.1 [+ or -] 0.4, 9.7 [+ or -] 0.4, and 9.6 [+ or -] 0.3 g/dl in MI, CSQ, and SERCA2 KO, respectively (P < 0.05). Colony numbers per 100,000 [CD34.sup.+] cells in the three CHF groups were reduced to 33 [+ or -] 3 (MI), 34 [+ or -] 3 (CSQ), and 39 [+ or -] 3 (SERCA2 KO) compared with 68 [+ or -] 4 in controls (P < 0.05). Plasma TNF-[alpha] nearly doubled in MI, and addition of anti-TNF-[alpha] antibody normalized colony formation. Inhibition of colony formation was completely abolished with blockade of endothelial NO synthase in CSQ and SERCA2 KO, but not in MI. In conclusion, the mechanism of anemia in CHF depends on the etiology of cardiac disease; whereas TNF-[alpha] impairs hematopoiesis in CHF following MI, NO inhibits blood cell formation in nonischemic murine CHF. blood cells; ischemia; nitric oxide doi:10.1152/ajpregu.00250.2009

Morocco is undergoing nutrition transition with more than one third of women and children presenting anaemia while about 20% of children under the age of 15 years have stunted growth. Meanwhile the prevalence of obesity is increasing yearly by 0.5 to 1 point among women. Many nutritional strategies have been proposed but none has been implemented. Nutrition education and food based strategies are by far the most sustainable. Dietary diversity is used for the assessment of diet quality and food security. Morocco is still suffering from a heavy burden of many micronutrient deficiencies and child stunting. The purpose of the study was to assess dietary diversity by comparing a dietary diversity score (DDS) and a weekly food frequency score (WFFS) and study their relationship to anaemia and stunting in school-age children in the province of Kenitra (Morocco). A stratified random sample of 263 pupils with average age of 12.9 [+ or -] 0.9 years including one-third from rural schools were administered a weekly food frequency questionnaire. A health team assessed the anthropometric status and blood haemoglobin levels. Dietary diversity was appraised with two types of indices: a dietary diversity score (DDS) based on the number of food categories consumed over a week, and a weekly food frequency score (WFFS) which also takes into account the frequency of food intake. The DDS was significantly higher in rural than in urban children, whereas the WFFS was lower, in rural children owing primarily to less frequent intake of fruits and vegetables than in the urban children. Maternal level of instruction was also positively associated with a higher consumption of fruits and vegetables and milk, and with a higher WFFS. Both indices were significantly associated with stunting but not with anaemia. In conclusion, these results suggest that diet quality is associated with height status and food diversity indices that take food frequency into account may provide a better reflection of diet quality. Key words: Dietary diversity, anaemia, stunting, Morocco, INTRODUCTION Malnutrition is widespread in Morocco, like in many other developing countries and Africa in particular. The 1990-1991 survey on living standards in Moroccan households reported a stunting rate (height-for-age [...]

Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses and angiogenesis in wild-type and anemic transgenic mice. These studies were done in erythropoietin-deficient mice (Epo-T[Ag.sup.h]) in normoxia and following acute (one day) and chronic (14 days, barometric pressure = 420 mmHg) hypoxia. In normoxia, Epo-T[Ag.sup.h] mice showed an increase in transcript and protein levels of hypoxia-inducible factor l[alpha] (HIF-1[alpha], vascular endothelial growth factor (VEGF), erythropoietin receptors (EpoR), phospho-STAT-5/STAT-5 ratio, and neuronal neuronal nitric oxide synthase (nNOS) along with a higher cerebral capillary density. In wild-type (WT) mice, acute hypoxia increased all of the studied factors, while in chronic hypoxia, HIF-1[alpha], EpoR, phospho-STAT-5/STAT-5 ratio, nNOS, and inducible NOS remained elevated, with an increase in capillary density. Surprisingly, in Epo-T[Ag.sup.h] mice, chronic hypoxia did not further increase any factor except the nitric oxide metabolites, while HIF-1[alpha], EpoR, and phospho-STAT-5/STAT-5 ratio were reduced. Normoxic Epo-T[Ag.sup.h] mice developed cerebral angiogenesis through the HIF-1[alpha] VEGF pathway. In acute hypoxia, WT mice up-regulated all of the studied factors, including cerebral NO. Polycythemia and angiogenesis occurred with acclimatization to chronic hypoxia only in WT mice. In Epo-T[Ag.sup.h], the decrease in HIF-l[alpha], VEGF proteins, and phospho-STAT-5 ratio in chronic hypoxia suggest that neuroprotective and angiogenesis pathways are altered. chronic anemia; erythropoietin; angiogenesis; hypoxia; cerebral cortex

It is known that renal tissue plays a role in normal iron homeostasis. The current study examines kidney function in iron metabolism under hemolytic anemia studying renal expression of Prohepcidin, Ferroportin (MTP1), and divalent metal transporter 1 (DMT1). The relationship between these proteins and iron pigments was also investigated. Immunohistochemical procedures to study renal expression of Prohepcidin, MTP1, and DMT1 were performed in healthy and anemic mice. Renal tissue iron was determined by Prussian blue iron staining. To assess anemia evolution and erythropoietic recovery, we used conventional tests. In healthy mice, Prohepcidin expression was marked in proximal tubules and inner medulla and absent in outer medulla. Cortical tissue of healthy mice also showed MTP1 immunostaining, mainly in the S2 segment of proximal tubules. Medullar tissue showed MTP1 expression in the inner zone. In addition, S2 segments showed intense DMT1 immunoreactivity with homogeneous DMT1 distribution throughout renal medulla. The main cortical findings in hemolytic anemia were in S2 segments of proximal tubules where we found that decreased Prohepcidin expression coincided with an increment in Ferroportin and DMT1 expression. This expression pattern was concomitant with increased iron in the same tubular zone. However, in medullar tissue both Prohepcidin and MTP1 decreased and DMT1 was detected mainly in larger diameter tubules. Our findings clearly demonstrate that in hemolytic anemia, renal Prohepcidin acts in coordination with renal Ferroportin and DMT1, indicating the key involvement of kidney in iron homeostasis when iron demand is high. Further research is required to learn more about these regulatory mechanisms. divalent metal transporter 1; anemia

Byline: Kristen C. Sihler, MD, MS (Division of Acute care Surgery, University of Michigan, Ann Arbor, Michigan, ksihler@umich.edu); Lena M. Napolitano, MD (Division of Acute care Surgery, University of Michigan, [...]

In mammals, two homologous cytosolic regulatory proteins, iron regulatory protein 1 (also known as IRP1 and Aco1) and iron regulatory protein 2 (also known as IRP2 and Ireb2), sense cytosolic iron levels and posttranscriptionally regulate iron metabolism genes, including transferrin receptor 1 (TfR1) and ferritin H and L subunits, by binding to iron-responsive elements (IREs) within target transcripts. Mice that lack IRP2 develop microcytic anemia and neurodegeneration associated with functional cellular iron depletion caused by low TfR1 and high ferritin expression. IRP1 knockout ([IRP1.sup.-/-]) animals do not significantly misregulate iron metabolism, partly because IRP1 is an iron-sulfur protein that functions mainly as a cytosolic aconitase in mammalian tissues and IRP2 activity increases to compensate for loss of the IRE binding form of IRP1. The neurodegenerative disease of [IRP2.sup.-/-] animals progresses slowly as the animals age. In this study, we fed [IRP2.sup.-/-] mice a diet supplemented with a stable nitroxide, Tempol, and showed that the progression of neuromuscular impairment was markedly attenuated. In cell lines derived from [IRP2.sup.-/-] animals, and in the cerebellum, brainstem, and forebrain of animals maintained on the Tempol diet, IRP1 was converted from a cytosolic aconitase to an IRE binding protein that stabilized the TfR1 transcript and repressed ferritin synthesis. We suggest that Tempol protected [IRP2.sup.-/-] mice by disassembling the cytosolic iron-sulfur cluster of IRP1 and activating IRE binding activity, which stabilized the TfR1 transcript, repressed ferritin synthesis, and partially restored normal cellular iron homeostasis in the brain. anemia | axonopathy | ferritin | iron-sulfur cluster | transferrin receptor

To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in the regulation of erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates, By the age of 10 weeks, cGKI-deficient mice exhibited pronounced anemia and splenomegaly. Compared with control mice, the cGKI mutants had significantly lower red blood cell count, packed cell volume, and hemoglobin concentration. Anemia was associated with a higher reticulocyte number and an increase of plasma erythropoietin concentration. The spleens of cGKI mutant mice were massively enlarged and contained a higher fraction of [Ter119.sup.+] erythroid cells, whereas the relative proportion of leukocyte subpopulations was not changed. The [Ter119.sup.+] cGKI-deficient splenocytes showed a marked increase in annexin V binding, pointing to phosphatidylserine (PS) exposure at the outer membrane leaflet, a hallmark of suicidal erythrocyte death or eryptosis. Compared with control erythrocytes, cGKI-deficient erythrocytes exhibited in vitro a higher cytosolic [Ca.sup.2+] concentration, a known trigger of eryptosis, and showed increased PS exposure, which was paralleled by a faster clearance in vivo. Together, these results identify a role of cGKI as mediator of erythrocyte survival and extend the emerging concept that cGMP/cGKI signaling has an antiapoptotic/prosurvival function in a number of cell types in vivo. apoptosis | [Ca.sup.2+] channels | phosphatidylserine | spleen

Anemia is a serious concern among indigenous populations in North America, and it appears to be widespread among the Inuit despite abundant intakes of heme iron. It is therefore hypothesized that anemia for the Inuit involves other dietary factors not usually associated with animal foods, such as low intakes of vitamin A and/or folate, riboflavin, and vitamin C. Also, Helicobacter pylori infection and/or parasitosis may result in gastrointestinal blood loss and/or functional iron deficiency. This review aims to describe factors that may cause anemia in Inuit populations despite high meat intakes, abundant bioavailable iron, and other important hematological nutrients.

A 39-year-old woman with a past medical history significant for scleroderma presented to her primary care physician with complaints of gastric pain and nausea. She was referred to a gastroenterologist [...]