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Orphanet Journal of Rare Diseases May 2010Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost... (Review)
Review
Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia.It is probably the most common monogenic gene disorder in the world and is especially frequent in Mediterranean countries, South-East Asia, Africa, the Middle East and in the Indian subcontinent. During the last few decades the incidence of alpha thalassaemia in North-European countries and Northern America has increased because of demographic changes. Compound heterozygotes and some homozygotes have a moderate to severe form of alpha thalassaemia called HbH disease. Hb Bart's hydrops foetalis is a lethal form in which no alpha-globin is synthesized. Alpha thalassaemia most frequently results from deletion of one or both alpha genes from the chromosome and can be classified according to its genotype/phenotype correlation. The normal complement of four functional alpha-globin genes may be decreased by 1, 2, 3 or all 4 copies of the genes, explaining the clinical variation and increasing severity of the disease. All affected individuals have a variable degree of anaemia (low Hb), reduced mean corpuscular haemoglobin (MCH/pg), reduced mean corpuscular volume (MCV/fl) and a normal/slightly reduced level of HbA2. Molecular analysis is usually required to confirm the haematological observations (especially in silent alpha-thalassaemia and alpha-thalassaemia trait). The predominant features in HbH disease are anaemia with variable amounts of HbH (0.8-40%). The type of mutation influences the clinical severity of HbH disease. The distinguishing features of the haemoglobin Bart's hydrops foetalis syndrome are the presence of Hb Bart's and the total absence of HbF. The mode of transmission of alpha thalassaemia is autosomal recessive. Genetic counselling is offered to couples at risk for HbH disease or haemoglobin Bart's Hydrops Foetalis Syndrome. Carriers of alpha+- or alpha0-thalassaemia alleles generally do not need treatment. HbH patients may require intermittent transfusion therapy especially during intercurrent illness. Most pregnancies in which the foetus is known to have the haemoglobin Bart's hydrops foetalis syndrome are terminated due to the increased risk of both maternal and foetal morbidity.
Topics: Gene Deletion; Hemoglobins, Abnormal; Humans; Mutation; alpha-Globins; alpha-Thalassemia
PubMed: 20507641
DOI: 10.1186/1750-1172-5-13 -
Nutrition Reviews Jul 2023Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and... (Meta-Analysis)
Meta-Analysis
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.
CONTEXT
Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.
OBJECTIVE
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.
DATA SOURCES
A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.
DATA EXTRACTION
Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.
DATA ANALYSIS
Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.
CONCLUSION
Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.
PROSPERO REGISTRATION NO
CRD42020196984.
Topics: Adult; Child; Female; Humans; Male; Pregnancy; Anemia, Iron-Deficiency; Dietary Supplements; Ferritins; Hemoglobins; Iron; Iron Deficiencies; Randomized Controlled Trials as Topic; Salts; Ferrous Compounds
PubMed: 36728680
DOI: 10.1093/nutrit/nuac106 -
Indian Pediatrics Sep 2022There is limited literature in children on efficacy of different routes of vitamin B12 administration for vitamin B12 deficiency macrocytic-megaloblastic anemia. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There is limited literature in children on efficacy of different routes of vitamin B12 administration for vitamin B12 deficiency macrocytic-megaloblastic anemia.
OBJECTIVE
To compare parenteral with oral vitamin B12 therapy in children with macrocytic-megaloblastic anemia.
STUDY DESIGN
Single-center, open-label randomized controlled trial.
PARTICIPANT
80 children aged 2 month-18 year with clinical and laboratory features of nutritional macrocytic anemia.
INTERVENTION
All children received an initial single parenteral dose of 1000 µg vitamin B12 followed by randomization to either parenteral or oral vitamin B12 for subsequent doses. Group A was given 1000 µg intramuscular (IM) vitamin B12 (3 doses on alternate days for those aged <10 year, five doses for age >10 year), followed by monthly 1000 µg IM for the subsequent two doses. Group B was given daily oral vitamin B12 1500 µg (500 µg in <2 years age) for three months. Folic acid and iron supple-mentation, and relevant dietary advice were given to both groups in a similar fashion.
OUTCOME
Improvement in serum vitamin B12 levels and total hemoglobin was compared three months post-treatment.
RESULT
The median(IQR) increase in serum vitamin B12 level was significantly higher in group A [600 (389,775) vs 399 (313, 606) pg/mL; P= 0.016]. The median (IQR) rise of hemoglobin was also more in group A [2.7 (0.4,4.6) vs 0.5 (-0.1,1.2) g/dL; P=0.001].
CONCLUSION
Increase in serum vitamin B12 levels and hemoglobin was better in children with nutritional macrocytic anemia receiving parenteral as compared to oral vitamin B12.
Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Folic Acid; Hemoglobins; Humans; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 35642923
DOI: No ID Found -
Journal of Internal Medicine Nov 2021Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased... (Review)
Review
BACKGROUND
Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased risk of cardiovascular disease later in life. Extracellular haemoglobin (Hb) and its metabolites heme and iron are highly toxic molecules and several defence mechanisms have evolved to protect the tissue.
OBJECTIVES
We will discuss the roles of free iron, heme, Hb, and the scavenger proteins haemopexin and alpha-1-microglobulin in pregnancies complicated by PE and fetal growth restriction (FGR).
CONCLUSION
In PE, oxidative stress causes syncytiotrophoblast (STB) stress and increased shedding of placental STB-derived extracellular vesicles (STBEV). The level in maternal circulation correlates with the severity of hypertension and supports the involvement of STBEVs in causing maternal symptoms in PE. In PE and FGR, iron homeostasis is changed, and iron levels significantly correlate with the severity of the disease. The normal increase in plasma volume taking place during pregnancy is less for PE and FGR and therefore have a different impact on, for example, iron concentration, compared to normal pregnancy. Excess iron promotes ferroptosis is suggested to play a role in trophoblast stress and lipotoxicity. Non-erythroid α-globin regulates vasodilation through the endothelial nitric oxide synthase pathway, and hypoxia-induced α-globin expression in STBs in PE placentas is suggested to contribute to hypertension in PE. Underlying placental pathology in PE with and without FGR might be amplified by iron and heme overload causing oxidative stress and ferroptosis. As the placenta becomes stressed, the release of STBEVs increases and affects the maternal vasculature.
Topics: Alpha-Globulins; Female; Fetal Growth Retardation; Heme; Hemoglobins; Hemopexin; Humans; Hypertension; Iron; Placenta; Pre-Eclampsia; Pregnancy; alpha-Globins
PubMed: 34146434
DOI: 10.1111/joim.13349 -
Neuropharmacology Feb 2021Hemopressin (PVNFKFLSH in rats, and PVNFKLLSH in humans and mice), a fragment derived from the α-chain of hemoglobin, was the first peptide described to have type 1... (Review)
Review
Hemopressin (PVNFKFLSH in rats, and PVNFKLLSH in humans and mice), a fragment derived from the α-chain of hemoglobin, was the first peptide described to have type 1 cannabinoid receptor activity. While hemopressin was shown to have inverse agonist/antagonistic activity, extended forms of hemopressin (i.e. RVD-hemopressin, also called pepcan-12) exhibit type 1 and type 2 cannabinoid receptor agonistic/allosteric activity, and recent studies suggest that they can activate intracellular mitochondrial cannabinoid receptors. Therefore, hemopressin and hemopressin-related peptides could have location-specific and biased pharmacological action, which would increase the possibilities for fine-tunning and broadening cannabinoid receptor signal transduction. Consistent with this, hemopressins were shown to play a role in a number of physiological processes including antinociceptive and anti-inflammatory activity, regulation of food intake, learning and memory. The shortest active hemopressin fragment, NFKF, delays the first seizure induced by pilocarpine, and prevents neurodegeneration in an experimental model of autoimmune encephalomyelitis. These functions of hemopressins could be due to engagement of both cannabinoid and non-cannabinoid receptor systems. Self-assembled nanofibrils of hemopressin have pH-sensitive switchable surface-active properties, and show potential as inflammation and cancer targeted drug-delivery systems. Upon disruption of the self-assembled hemopressin nanofibril emulsion, the intrinsic analgesic and anti-inflammatory properties of hemopressin could help bolster the therapeutic effect of anti-inflammatory or anti-cancer formulations. In this article, we briefly review the molecular and behavioral pharmacological properties of hemopressins, and summarize studies on the intricate and unique mode of generation and binding of these peptides to cannabinoid receptors. Thus, the review provides a window into the current status of hemopressins in expanding the repertoire of signaling and activity by the endocannabinoid system, in addition to their new potential for pharmaceutic formulations.
Topics: Animals; Cannabinoid Receptor Agonists; Endocannabinoids; Hemoglobins; Humans; Mice; Peptide Fragments; Rats; Receptors, Cannabinoid
PubMed: 33212113
DOI: 10.1016/j.neuropharm.2020.108406 -
Biochemical and Biophysical Research... Dec 2021Cell-free heme-containing proteins mediate endothelial injury in a variety of disease states including subarachnoid hemorrhage and sepsis by increasing endothelial...
BACKGROUND
Cell-free heme-containing proteins mediate endothelial injury in a variety of disease states including subarachnoid hemorrhage and sepsis by increasing endothelial permeability. Inflammatory cells are also attracted to sites of vascular injury by monocyte chemotactic protein 1 (MCP-1) and other chemokines. We have identified a novel peptide hormone, adropin, that protects against hemoglobin-induced endothelial permeability and MCP-1-induced macrophage migration.
METHODS
Human microvascular endothelial cells were exposed to cell-free hemoglobin (CFH) with and without adropin treatment before measuring monolayer permeability using a FITC-dextran tracer assay. mRNA and culture media were collected for molecular studies. We also assessed the effect of adropin on macrophage movement across the endothelial monolayer using an MCP-1-induced migration assay.
RESULTS
CFH exposure decreases adropin expression and increases paracellular permeability of human endothelial cells. Treating cells with synthetic adropin protects against the increased permeability observed during the natural injury progression. Cell viability was similar in all groups and Hmox1 expression was not affected by adropin treatment. MCP-1 potently induced macrophage migration across the endothelial monolayer and adropin treatment effectively reduced this phenomenon.
CONCLUSIONS
Endothelial injury is a hallmark of many disease states. Our results suggest that adropin treatment could be a valuable strategy in preventing heme-mediated endothelial injury and macrophage infiltration. Further investigation of adropin therapy in animal models and human tissue specimens is needed.
Topics: Cell Line; Cell Membrane Permeability; Cell Movement; Chemokine CCL2; Cytoprotection; Endothelial Cells; Hemoglobins; Humans; Intercellular Signaling Peptides and Proteins; Macrophages
PubMed: 34710824
DOI: 10.1016/j.bbrc.2021.10.032 -
Gaceta Sanitaria 2021The purpose of this review is to describe an intervention that utilizes dates as a source of nutrition for pregnant women to increase hemoglobin levels in the blood in... (Review)
Review
OBJECTIVE
The purpose of this review is to describe an intervention that utilizes dates as a source of nutrition for pregnant women to increase hemoglobin levels in the blood in anemia incidence. The findings in this study are related to the use of dates to increase hemoglobin levels in the blood in pregnant women.
METHODS
This study uses search databases used in PubMed, Science Direct, and Google Scholar. The keywords used in the initial search for articles are dates and hemoglobin obtained as many as 189 articles. At the time of using the keywords dates, hemoglobin, anemia by obtaining 15 articles and which are used only 10 articles according to the analysis of the purpose, suitability of the topic, the method of research used, sample size, research ethics, the results of each article, as well as limitations that occur.
RESULT
Anemia in pregnant women causes hemoglobin (Hb) levels to decrease in the blood; the capacity of oxygen transfer to meet the needs of vital organs in the mother and fetus is reduced. All literature reviewed shows that administration of dates increases hemoglobin levels; only one literature shows no influence of consumes date juice on hemoglobin level. The majority of the literature reviewed is mild anemia.
CONCLUSION
There are effective results in the implementation of health promotion of increased hemoglobin levels in the blood in pregnant women by utilizing dates as a source of nutrition.
Topics: Anemia; Female; Fruit; Hemoglobins; Humans; Nutritional Status; Phoeniceae; Pregnancy; Pregnancy Complications, Hematologic
PubMed: 34929829
DOI: 10.1016/j.gaceta.2021.10.032 -
BMC Endocrine Disorders Mar 2021An association between hemoglobin and metabolic syndrome (MetS) has been reported. However, the relationships between hemoglobin and individual MetS components remain...
BACKGROUND
An association between hemoglobin and metabolic syndrome (MetS) has been reported. However, the relationships between hemoglobin and individual MetS components remain unclear. Therefore, we investigated these associations at baseline and at the 3-year follow-up.
METHODS
We enrolled 9960 middle-aged and elderly subjects (6726 women and 3234 men) and performed a 3-year follow-up cohort study. All subjects completed a questionnaire and underwent anthropometric measurements and laboratory tests. Logistic regression models were developed to assess the association between hemoglobin and MetS and its components.
RESULTS
MetS was present in 45.1% of women and 41.4% of men at baseline. The hemoglobin concentration was positively correlated with SBP, DBP, TGs, WC, FPG, insulin, HOMA-IR, BMI and uric acid (p < 0.05). The mean hemoglobin concentration was higher in subjects with hypertension, high TGs, abdominal obesity or elevated FPG (p < 0.01). At follow-up, elevated hemoglobin correlated with an increased incidence and ORs for MetS, high TGs, low HDL-c, hyperuricemia and NAFLD but not abdominal obesity, BP or FPG in women. Increased hemoglobin corresponded with an increased incidence and ORs for MetS, abdominal obesity, low HDL-c, hyperuricemia and NAFLD but not BP, high TGs or FPG in men.
CONCLUSIONS
Hemoglobin may play a role in predicting new-onset MetS in both women and men. Hemoglobin was notably correlated with future risk of high TGs, low HDL-c, hyperuricemia, and NAFLD among women and abdominal obesity, low HDL-c, hyperuricemia, and NAFLD among men.
Topics: Aged; China; Cohort Studies; Cross-Sectional Studies; Female; Follow-Up Studies; Health Surveys; Hemoglobins; Humans; Incidence; Male; Metabolic Syndrome; Middle Aged
PubMed: 33740939
DOI: 10.1186/s12902-021-00719-4 -
IUBMB Life May 2022Hemoglobin oxidation due to oxidative stress and disease conditions leads to the generation of ROS (reactive oxygen species) and membrane attachment of hemoglobin...
Hemoglobin oxidation due to oxidative stress and disease conditions leads to the generation of ROS (reactive oxygen species) and membrane attachment of hemoglobin in-vivo, where its redox activity leads to peroxidative damage of membrane lipids and proteins. Spectrin, the major component of the red blood cell (RBC) membrane skeleton, is known to interact with hemoglobin and, here this interaction is shown to increase hemoglobin peroxidase activity in the presence of reducing substrate ABTS (2', 2'-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid). It is also shown that in the absence of reducing substrate, spectrin forms covalently cross-linked aggregates with hemoglobin which display no peroxidase activity. This may have implications in the clearance of ROS and limiting peroxidative damage. Spectrin is found to modulate the peroxidase activity of different hemoglobin variants like A, E, and S, and of isolated globin chains from each of these variants. This may be of importance in disease states like sickle cell disease and HbE-β-thalassemia, where increased oxidative damage and free globin subunits are present due to the defects inherent in the hemoglobin variants associated with these diseases. This hypothesis is corroborated by lipid peroxidation experiments. The modulatory role of spectrin is shown to extend to other heme proteins, namely catalase and cytochrome-c. Experiments with free heme and Raman spectroscopy of heme proteins in the presence of spectrin show that structural alterations occur in the heme moiety of the heme proteins on spectrin binding, which may be the structural basis of increased enzyme activity.
Topics: Antioxidants; Catalase; Heme; Hemeproteins; Hemoglobins; Peroxidase; Peroxidases; Reactive Oxygen Species; Spectrin
PubMed: 35184374
DOI: 10.1002/iub.2607 -
Metabolic Engineering Jul 2021With the increasing demand for blood transfusions, the production of human hemoglobin (Hb) from sustainable sources is increasingly studied. Microbial production is an...
With the increasing demand for blood transfusions, the production of human hemoglobin (Hb) from sustainable sources is increasingly studied. Microbial production is an attractive option, as it may provide a cheap, safe, and reliable source of this protein. To increase the production of human hemoglobin by the yeast Saccharomyces cerevisiae, the degradation of Hb was reduced through several approaches. The deletion of the genes HMX1 (encoding heme oxygenase), VPS10 (encoding receptor for vacuolar proteases), PEP4 (encoding vacuolar proteinase A), ROX1 (encoding heme-dependent repressor of hypoxic genes) and the overexpression of the HEM3 (encoding porphobilinogen deaminase) and the AHSP (encoding human alpha-hemoglobin-stabilizing protein) genes - these changes reduced heme and Hb degradation and improved heme and Hb production. The reduced hemoglobin degradation was validated by a bilirubin biosensor. During glucose fermentation, the engineered strains produced 18% of intracellular Hb relative to the total yeast protein, which is the highest production of human hemoglobin reported in yeast. This increased hemoglobin production was accompanied with an increased oxygen consumption rate and an increased glycerol yield, which (we speculate) is the yeast's response to rebalance its NADH levels under conditions of oxygen limitation and increased protein-production.
Topics: Blood Proteins; Fermentation; Fungal Proteins; Heme; Hemoglobins; Humans; Molecular Chaperones; Peroxidases; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 33984513
DOI: 10.1016/j.ymben.2021.05.002