Iron Deficiency State Research Articles

Potential hematopoietic effects of SGLT2 inhibitors in patients with cardiac amyloidosis

Abstract Introduction Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been revealed to have potential hematopoietic effects in patients with heart failure (HF), leading to an improvement in clinical outcome. However, these benefits have not been studied in patients with cardiac amyloidosis (CA), despite CA often causing symptoms of heart failure (HF) and contributing to an iron-deficient state, which further complicates by limiting erythropoiesis and lowering haemoglobin and haemotocrit levels. We aimed to determine the potential of SGLT2i in improving haematological parameters and functional capacity (FC) in amyloidosis patients. Methods A prospective analysis was conducted to compare the effects of SGLT2i in a cohort of patients who received the best medical therapy (BMT) alongside SGLT2i (n=20), as opposed to patients receiving only BMT without SGLT2i (n=20). All of patients underwent blood testing and cardiopulmonary exercise testing (CPET) at baseline and after 6 months (IQR:5.0 – 6.0). Results The SGLT2i-based therapy resulted in a significant improvement and difference in hematological parameters upon follow-up assessment compared to the control group. In the SGLT2i group, the mean haemoglobin level increased from 13.3 g/dL to 14.5 g/dL, whereas in the control group, it decreased from 12.7 g/dL to 10.9 g/dL (P < 0.001). Furthermore, the haematocrit difference showed a significant increase in the SGLT2i group (+3.8%) compared to a decrease in the control group (-4.4%) (P < 0.001). Additionally, the iron status improved in the SGLT2i-treated group (+6.7 µg/dL) compared to a decrease in the control group (-14.9 µg/dL), although the difference was significant only with a p-value of 0.034. However, neither group demonstrated significant improvement nor regression in CPET parameters. The peak oxygen consumption (peak VO2, (ml/min)/kg) showed no significant change in either group (P = 0.286), as well as VE/VCO2 slope (P = 0.295). Conclusions Treatment with SGLT2i could be utilized in the treatment of patients with amyloidosis. This potential benefit in improving hematological parameters warrants further investigation and consideration in clinical practice.

Utility of Reticulocyte Hemoglobin Equivalent in Screening for Iron Deficiency in Pregnancy.

Ferritin, commonly used for diagnosing iron deficiency (ID) in pregnancy, is limited by high cost and false elevations during inflammation. Reticulocyte hemoglobin equivalent (Ret-He), an alternative marker for ID, is unaffected by inflammation and analyzed on the same collection tube as the standard complete blood count (CBC). We aimed to determine the accuracy of Ret-He in detecting ID in pregnancy compared to ferritin in a U.S. This prospective cohort study enrolled 200 pregnant participants, recruited in any trimester if a CBC was drawn as part of routine prenatal care. For those who agreed to participate, Ret-He and ferritin were collected concurrently with the CBC. ID was defined as ferritin level below 30 ng/mL. Patients were classified into three groups based on hemoglobin and ferritin results to determine the severity of ID: no ID, ID alone, and ID anemia (IDA). Four participants with anemia but normal ferritin were excluded. Receiver operating curve analysis, including the area under the curve (AUC), was performed to assess the accuracy of Ret-He in detecting ID. A one-way ANOVA (analysis of variance) with post-hoc analysis was used to compare differences in Ret-He between the three groups of ID severity. The prevalence of ID in our cohort was 82% (161/196). The AUC for Ret-He was 0.65 (95% confidence interval: 0.55-0.75), indicating suboptimal discrimination between patients with and without ID. Ret-He was significantly different among the three groups (p < 0.001). In post-hoc analysis, Ret-He was significantly lower in the IDA group compared to the ID group (p < 0.001) but there was only a trend of lower Ret-He in the ID group compared to the non-ID group (p = 0.38). Ret-He has low accuracy in diagnosing ID in pregnancy. It may be useful in detecting severe ID resulting in anemia but not a mild iron-deficient state resulting in ID only. · The prevalence of ID in our cohort was 82%.. · Ret-He has low accuracy in diagnosing ID in pregnancy.. · Ferritin is preferable when readily available..

Efficacy of iron supplementation on physical capacity in non-anaemic iron-deficient individuals: protocol for an individual patient data meta-analysis

BackgroundA deficiency in iron stores is associated with various adverse health complications, which, if left untreated, can progress to states of anaemia, whereby there is significant detriment to an individual’s work capacity and quality of life due to compromised erythropoiesis. The most common methods employed to treat an iron deficiency include oral iron supplementation and, in persistent and/or unresponsive cases, intravenous iron therapy. The efficacy of these treatments, particularly in states of iron deficiency without anaemia, is equivocal. Indeed, both randomised control trials and aggregate data meta-analyses have produced conflicting evidence. Therefore, this study aims to assess the efficacy of both oral and intravenous iron supplementation on physical capacity, quality of life, and fatigue scores in iron-deficient non-anaemic individuals using individual patient data (IPD) meta-analysis techniques.MethodsAll potential studies, irrespective of design, will be sourced through systematic searches on the following databases: Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, Web of Science: Science Citation Index Expanded, Web of Science: Conference Proceedings Citation Index-Science, ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform. Individual patient data from all available trials will be included and subsequently analysed in a two-stage approach. Predetermined subgroup and sensitivity analyses will be employed to further explain results.DiscussionThe significance of this IPD meta-analysis is one of consolidating a clear consensus to better inform iron-deficient individuals of the physiological response associated with iron supplementation. The IPD approach, to the best of our knowledge, is novel for this research topic. As such, the findings will significantly contribute to the current body of evidence.Systematic review registrationPROSPERO CRD42020191739.

Redefining Iron Deficiency in Patients With Chronic Heart Failure.

A serum ferritin level <15 to 20 μg/L historically identified patients who had absent bone marrow iron stores, but serum ferritin levels are distorted by the systemic inflammatory states seen in patients with chronic kidney disease or heart failure. As a result, nearly 25 years ago, the diagnostic ferritin threshold was increased 5- to 20-fold in patients with chronic kidney disease (ie, iron deficiency was identified if the serum ferritin level was <100 μg/L, regardless of transferrin saturation [TSAT], or 100 to 299 μg/L if TSAT was <20%). This guidance was motivated not by the findings of studies of total body or tissue iron depletion, but by a desire to encourage the use of iron supplements to potentiate the response to erythropoiesis-stimulating agents in patients with renal anemia. However, in patients with heart failure, this definition does not reliably identify patients with an absolute or functional iron-deficiency state, and it includes individuals with TSATs (≥20%) and serum ferritin levels in the normal range (20-100 mg/L) who are not iron deficient, have an excellent prognosis, and do not respond favorably to iron therapy. Furthermore, serum ferritin levels may be distorted by the use of both neprilysin and sodium-glucose cotransporter 2 inhibitors, both of which may act to mobilize endogenous iron stores. The most evidence-based and trial-tested definition of iron deficiency is the presence of hypoferremia, as reflected by as a TSAT <20%. These hypoferremic patients are generally iron deficient on bone marrow examination, and after intravenous iron therapy, they exhibit an improvement in exercise tolerance and functional capacity (when meaningfully impaired) and show the most marked reduction (ie, 20%-30%) in the risk of cardiovascular death or total heart failure hospitalizations. Therefore, we propose that the current ferritin-driven definition of iron deficiency in heart failure should be abandoned and that a definition based on hypoferremia (TSAT <20%) should be adopted.

Critical re-evaluation of the identification of iron deficiency states and effective iron repletion strategies in patients with chronic heart failure.

According to current guidelines, iron deficiency is defined by a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% if the serum ferritin level is 100-299 μg/L. These criteria were developed to encourage the use of intravenous iron as an adjunct to erythropoiesis-stimulating agents in the treatment of renal anaemia. However, in patients with heart failure, these criteria are not supported by any pathophysiological or clinical evidence that they identify an absolute or functional iron deficiency state. A low baseline TSAT-but not serum ferritin level-appears to be a reliable indicator of the effect of intravenous iron to reduce major heart failure events. In randomized controlled trials, intravenous iron decreased the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT <20% (risk ratio 0.67 [0.49-0.92]) but not in patients with a TSAT ≥20% (risk ratio 0.99 [0.74-1.30]), with the magnitude of the risk reduction being proportional to the severity of hypoferraemia. Patients who were enrolled in clinical trials solely because they had a serum ferritin level <100 μg/L showed no significant benefit on heart failure outcomes, and it is noteworthy that serum ferritin levels of 20-300 μg/L lie entirely within the range of normal values for healthy adults. Current guidelines reflect the eligibility criteria of clinical trials, which inadvertently adopted unvalidated criteria to define iron deficiency. Reliance on these guidelines would lead to the treatment of many patients who are not iron deficient (serum ferritin level <100 μg/L but normal TSAT) and ignores the possibility of iron deficiency in patients with a low TSAT but with serum ferritin level of >300 μg/L. Importantly, analyses of benefit based on trial eligibility-driven guidelines substantially underestimate the magnitude of heart-failure-event risk reduction with intravenous iron in patients who are truly iron deficient. Based on all available data, we recommend a new mechanism-based and trial-tested approach that reflects the totality of evidence more faithfully than the historical process adopted by clinical investigators and by the guidelines. Until additional evidence is forthcoming, an iron deficiency state in patients with heart failure should be defined by a TSAT <20% (as long as the serum ferritin level is <400 μg/L), and furthermore, the use of a serum ferritin level <100 μg/L alone as a diagnostic criterion should be discarded.

Iron homeostasis, recycling and vulnerability in the stressed kidney: A neglected dimension of iron-deficient heart failure.

The available evidence suggests that the kidney may contribute importantly to the development of an iron deficiency state in patients with heart failure and may be injured by therapeutic efforts to achieve iron repletion. The exceptional workload of the proximal renal tubule requires substantial quantities of iron for ATP synthesis, which it derives from Fe3+ bound to transferrin in the bloodstream. Following ferrireduction, Fe2+ is conveyed by divalent transporters (e.g. DMT1) out of the endosome of the proximal renal tubule, and highly reactive Fe2+ can be directed to the mitochondria, sequestered safely in a ferritin nanocage or exported through the actions of hepcidin-inhibitable ferroportin. The actions of ferroportin, together with transferrin endocytosis and DMT1-mediated transport, play a key role in the recycling of iron from the tubular fluid into the bloodstream and preventing the loss of filtered iron in the urine. Activation of endogenous neurohormonal systems and proinflammatory signalling in heart failure decrease megalin-mediated uptake and DMT1 expression, and increase hepcidin-mediated suppression of ferroportin, promoting the loss of iron in the urine and contributing to the development of an iron deficiency state. Furthermore, the failure of ferroportin-mediated efflux at the basolateral membrane heightens the susceptibility of the renal tubules to cytosolic excesses of Fe2+, causing lipid peroxidation and synchronized cell death (ferroptosis) through the iron-dependent free radical theft of electrons from lipids in the cell membrane. Ferroptosis is a central mechanism to most disorders that can cause acute and chronic kidney disease. Short-term bolus administration of intravenous iron can cause oxidative stress and is accompanied by markers of renal injury. Experimentally, long-term maintenance of an iron-replete state is accompanied by accelerated loss of nephrons, oxidative stress, inflammation and fibrosis. Intravenous iron therapy increases glomerular filtration rate rapidly in patients with heart failure (perhaps because of a haemodynamic effect) but not in patients with chronic kidney disease, and the effects of intravenous iron on the progression of renal dysfunction in the long-term trials - AFFIRM-AHF, IRONMAN and HEART-FID - have not yet been reported. Given the potential role of dysregulated renal iron homeostasis in the pathogenesis of iron deficiency and the known vulnerability of the kidney to intravenous iron, the appropriate level of iron repletion with respect to the risk of acute and chronic kidney injury in patients with heart failure requires further study.

Correlates of iron deficiency among adult patients with sickle cell nephropathy at a tertiary health facility in Lagos, Nigeria: A cross-sectional study

Background: Iron deficiency presents a muddled clinical picture in patients with sickle cell anemia (SCA). The picture is further complicated when these patients develop sickle cell nephropathy (SCN). This study aimed to identify the correlates of iron deficiency among adult patients with SCN in Lagos, Nigeria. Methods: This was a cross-sectional study conducted among adult patients with SCN who presented at the nephrology clinic of the tertiary health facility. Data on demographics, clinical history, laboratory investigations, and iron status were collected and analyzed using the Statistical Package for the Social Sciences (SPSS) version 28. Results: One hundred and nineteen adult patients with SCN were enrolled in the study. The mean age was 28.9 ± 9.5 years, and the majority were females. Iron deficiency was present in 36 (30.2%) subjects, while 7.6% had elevated iron status. Younger age and male sex were associated with iron deficiency state. Participants with an estimated glomerular filtration rate (eGFR) of ≥60 mL/min had a higher prevalence of iron deficiency (r = −0.28 P &lt; 0.01/r = −0.32 P &lt; 0.01). A logistic regression analysis showed no independent association between these factors and iron deficiency. Conclusion: This study showed that iron deficiency is common in adults with SCN, seen in one-third of participants. Therefore, although iron overload is frequently acknowledged as a significant issue in SCA, it should not be automatically assumed in cases where nephropathy is present. The study findings also highlight the need for routine screening for iron deficiency among SCN patients, especially among males, younger patients or those with an eGFR ≥60 mL/min, to optimize their management and improve their outcomes.

Monitoring of iron deficiency in highly skilled martial artists

High-level sport is characterized by a significant level of both physical and nervous-emotional load, which puts forward high demands on the body of athletes. That is why athletes can be prone to iron deficiency conditions and anemia, especially women. The presence of iron deficiency can have serious consequences for athletes (increased risk of injury, slowing down the recovery process after physical loads, reduced immunity, and a significant decrease in performance). In turn, the problem is aggravated by the fact that iron deficiency in athletes can often exist without the manifestation of anemia and has a hidden course. This has necessitated detailed studies of athletes to identify conditions related to iron deficiency. The purpose of the study: determine the indicators of "red" blood, ferritin, and iron content in highly qualified athletes who specialize in martial arts to identify iron deficiency states to further establish the possible causes that can lead to their occurrence. The study involved 35 qualified athletes specializing in martial arts, including 20 men and 15 women. The following blood values were determined: ferritin concentration, hemoglobin, iron content, red blood cell count, and hematocrit level. As a result of our study, it was found that 20% of men and 66% of women studied had latent iron deficiency, which requires appropriate recommendations for treatment and prevention. Research results confirm the presence of iron deficiency problems among athletes (especially women). The findings indicate the importance not only of diagnosing iron deficiency anemia in athletes but also of paying attention to identifying latent iron deficiency. This will ensure timely diagnosis, correct therapy, and prevention of iron deficiency in athletes.

The Beneficial Impact of Iron-Fortified Complementary Feeding in the Burden of Iron Deficiency Anaemia (IDA) in Children of Bangladesh

Fortifying food with iron is the most cost-effective way to avoid iron deficiency anemia, a global public health crisis. In addition to choosing the appropriate dietary context for ingestion, it is critical to choose the appropriate iron form and food carrier. Among the increased hazards include low birth weight and preterm delivery. Children with IDA have slower development, worse cognitive performance, and lower levels of physical activity. In women, it also raises the risk of morbidity and death. The amount of iron required in the diet, one&amp;apos;s socioeconomic status, and overall health are all crucial factors to take into account. To combat IDA, a variety of dietary approaches, iron-fortified foods, supplements, and disease management techniques have all been employed. Nowadays, food fortification with iron is seen to be a long-term, sustainable solution. To be effective, the iron fortification program&amp;apos;s food transporters and fortificants must be deemed safe, pleasant, and acceptable by the target population. It also shouldn&amp;apos;t have a detrimental effect on the stability and acceptance of the finished product. This article provides a thorough summary of the current state of iron deficiency in women and children in Bangladesh. This study addresses current issues as well as the efficacy of current therapeutic strategies. Prevention-focused treatments ought to take precedence over treatment-focused ones in high-risk populations. Unknown are the long-term benefits, and unfavorable outcomes are possible. Despite the tremendous progress made, several plans and initiatives are still being supported. These issues are to coverage, quality, and compliance. The findings suggest that iron deficiency and anemia are still major problems in Bangladesh, despite the fact that certain severe deficiencies have been addressed by current intervention efforts. There is a need for more integrated solutions to assist current intervention efforts. Furthermore, new approaches to the management of certain types of iron deficiency anemia are proposed.

Diagnostic Utility of Reticulocyte Hemoglobin Equivalent Parameter in the Evaluation of Microcytic Hypochromic Anemia – Our Experience from Northeast India

Background: Reticulocytes are red blood cell precursors with an average lifespan of 1–2 days. Reticulocyte hemoglobin equivalent (Ret-He) is an early marker of iron deficiency (ID) erythropoiesis and reflects real-time information regarding the synthesis of young erythrocytes in the bone marrow. The objective of this study is to determine the diagnostic utility of Ret-He in patients having microcytic hypochromic anemia in comparison with serum ferritin and iron studies. Objectives: The objective of this study is to determine the diagnostic utility of the Ret-He parameter in patients having microcytic hypochromic anemia in comparison with the serum ferritin, iron studies and its role in routine hematological screening for nutritional deficiency anemia like ID. Design and Settings: The design involves observational study. Materials and Methods: A hospital-based observational study was carried out in a referral hospital. Hematological parameters were processed using Sysmex XN1000 (Sysmex Corporation, Kobe, Japan) analyzer and were compared with Serum iron studies using biochemistry analyzer (VITROS® 250 Chemistry System) from 201 participants who presented with microcytic hypochromic anemia. Main Outcome and Measures: Relationship of Ret-He parameter and its diagnostic utility for screening of iron-deficient states. Sample Size: The sample size was 201. Results: When serum ferritin is taken as “the gold standard” to detect ID, with Ret-He cutoff of 27.15 pg/cell, we found a statistically significant positive correlation between Ret-He and serum ferritin (P &lt; 0.001). We found a sensitivity of 57.37% and specificity of 75.95% with area under the curve of 0.681, positive predictive value of 100%, negative predictive value of 3.8%, and accuracy of 62.19% for Ret-He in detecting ID anemia (IDA). Also found a statistically significant negative correlation between Ret-He and total iron binding capacity (P &lt; 0.001). There was no statistical correlation between Ret-He and serum iron levels in our study. Conclusions: The present study suggests Ret-He is one of the better and more reliable hematological parameters indicating ID and, when used along with biochemical parameters like serum ferritin, can give valuable inputs in a better screening and diagnosis of IDA; hence proper treatment is possible. Limitations: The multicentric study is required to standardize Ret-He reference values, and follow-up to therapy of the subjects was not done. Additional hemoglobin variant analysis data would have been favorable to the study.

Why a complete medical exam is necessary prior to diagnosing ADHD

A recent literature review highlights the need to investigate a patient's medical issues before diagnosing, and treating, attention‐deficit hyperactivity disorder (ADHD). According to the review which looked at studies conducted over the past 20 years, several medical conditions can be misdiagnosed as ADHD. These conditions may have a similar presentation to ADHD, especially in regard to inattentive symptoms. Some examples are absence seizure disorder, diabetes, thyroid dysfunction, sleep deprivation, post‐concussion states, inflammatory bowel disease, iron deficiency states and anemia, and disordered breathing.

Evaluation of Left Ventricular Hemodynamics with Noninvasive Methods in Cases of Iron Deficiency

Objective: In this study, we aimed to evaluate the effect of iron deficiency on stress ejection fraction by assessing the change in left ventricular ejection fraction during maximum exercise in individuals with iron deficiency. Material and Methods: In this retrospective study, 212 patients, presenting with atypical chest pain and undergoing exercise gated myocardial perfusion scintigraphy, were included. Of the patients, 171 (80.7%) were female, with an average age of 50 (37-59) years. Patients were categorized into two groups: those with iron deficiency and those without. All patients exercised for a minimum of 6 minutes, reaching at least 85% of their maximum heart rate (220 - age). Hemogram, iron binding capacity, and serum ferritin values were recorded for all participants. In our study, SF less than 100 µg/L and TSAT less than 20% were considered low. Results: There was no significant difference in age and gender between the groups with and without iron deficiency (p: 0.758, p: 0.658). Echocardiography-calculated ejection fraction values were 66 (55-72). Rest ejection fraction obtained by force gated myocardial perfusion scintigraphy was 64 (52-70), and post-stress ejection fraction was calculated as 58 (50-69). The rate of decrease in post-stress EF compared to rest EF was calculated as 7.40% (7.81-19.12) in all patients. Echo, rest, and post-stress EF values in group 2 were significantly lower than those in group 1 (p: 0.003, 0.028, 0.0005, respectively). The rate of decrease in post-stress EF between the two groups was significantly higher in group 2 (p: 0.0005). Conclusion: While decreased iron stores and the presence of an iron deficiency state may be well-tolerated during daily activities, maximal exercise can exacerbate the condition if iron deficiency is underlying and undiagnosed. Early diagnosis of iron deficiency, common in society, before the onset of anemia, and prompt treatment are crucial for public health.

A kinetic model of iron trafficking in growing Saccharomyces cerevisiae cells; applying mathematical methods to minimize the problem of sparse data and generate viable autoregulatory mechanisms.

Iron is an essential transition metal for all eukaryotic cells, and its trafficking throughout the cell is highly regulated. However, the overall cellular mechanism of regulation is poorly understood despite knowing many of the molecular players involved. Here, an ordinary-differential-equations (ODE) based kinetic model of iron trafficking within a growing yeast cell was developed that included autoregulation. The 9-reaction 8-component in-silico cell model was solved under both steady-state and time-dependent dynamical conditions. The ODE for each component included a dilution term due to cell growth. Conserved rate relationships were obtained from the null space of the stoichiometric matrix, and the reduced-row-echelon-form was used to distinguish independent from dependent rates. Independent rates were determined from experimentally estimated component concentrations, cell growth rates, and the literature. Simple rate-law expressions were assumed, allowing rate-constants for each reaction to be estimated. Continuous Heaviside logistical functions were used to regulate rate-constants. These functions acted like valves, opening or closing depending on component "sensor" concentrations. Two cellular regulatory mechanisms were selected from 134,217,728 possibilities using a novel approach involving 6 mathematically-defined filters. Three cellular states were analyzed including healthy wild-type cells, iron-deficient wild-type cells, and a frataxin-deficient strain of cells characterizing the disease Friedreich's Ataxia. The model was stable toward limited perturbations, as determined by the eigenvalues of Jacobian matrices. Autoregulation allowed healthy cells to transition to the diseased state when triggered by a mutation in frataxin, and to the iron-deficient state when cells are placed in iron-deficient growth medium. The in-silico phenotypes observed during these transitions were similar to those observed experimentally. The model also predicted the observed effects of hypoxia on the diseased condition. A similar approach could be used to solve ODE-based kinetic models associated with other biochemical processes operating within growing cells.

Attention Deficit Hyperactivity Disorder Misdiagnosis: Why Medical Evaluation Should Be a Part of ADHD Assessment.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that interferes with multiple aspects of daily functioning and is associated with impairments in several domains. It may affect academic, educational, vocational, social, emotional, interpersonal, and health domains, and worsen risks to health outcomes. To identify and discuss medical conditions that commonly present with symptoms resembling ADHD. This review is selective and not systematic. It is conducted through a focused literature search through PubMed, Google Scholar, and EMBASE. Search term included "ADHD misdiagnosis", "medical conditions with ADHD like symptoms", "ADHD AND medical problems". giftedness, high IQ, and any article that does not list medical conditions. The limits applied were the following: the work must have been published in the past 20 years, be on humans, and be in the English language. There are several medical conditions that can be misdiagnosed as ADHD and may show a similar presentation to ADHD, particularly with inattentive symptoms. Examples include, but are not limited to, absence seizure disorder, diabetes, thyroid dysfunction, sleep deprivation, post-concussion states, inflammatory bowel disease, iron deficiency states and anemia, and disordered breathing. Our review suggests that a thorough medical evaluation should be conducted prior to the diagnosis of ADHD. Allied health professionals and psychologists who diagnose ADHD should seek medical clearance from a physician prior to making the ADHD diagnosis in order to reduce misdiagnosis rates and improve patient outcomes. ADHD diagnosis should follow guidelines and be carried out under a systematic standardized approach. A full medical evaluation should be conducted to assess for medical conditions that may look like ADHD or be associated with ADHD.

"Dietary Factors Influencing Platelet Counts: Knowledge to Improve Concentration for Platelet-Rich Plasma Injections"

The use of biologics, such as platelet-rich plasma (PRP) injections, has been widely used in the healing process surrounding injuries. Given the growth factor-rich property in nature, PRP injections induce neovascularization significantly. There has been research surrounding the role of diet and nutrition on platelet count and function. States of iron deficiency and dyslipidemia have supporting evidence of increasing platelet count. In contrast, ketogenic diets, cod liver, and vitamin D have been associated with decreased platelet counts. Considering that both diet and nutrients affect platelets, perhaps using this theory could be further researched in providing higher-quality PRP injections.

The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration

Chlorosis in azaleas is characterized by an interveinal yellowing of leaves that is typically caused by a deficiency of iron. This condition is usually due to the inability of cells to properly acquire iron as a consequence of unfavorable conditions, such as an elevated pH, rather than insufficient iron levels. The causes and effects of chlorosis were found to have similarities with those pertaining to a recently presented hypothesis that describes a pathogenic process in Alzheimer disease. This hypothesis states that iron becomes sequestered (e.g., by amyloid β and tau), causing a functional deficiency of iron that disrupts biochemical processes leading to neurodegeneration. Additional mechanisms that contribute to iron becoming unavailable include iron-containing structures not undergoing proper recycling (e.g., disrupted mitophagy and altered ferritinophagy) and failure to successfully translocate iron from one compartment to another (e.g., due to impaired lysosomal acidification). Other contributors to a functional deficiency of iron in patients with Alzheimer disease include altered metabolism of heme or altered production of iron-containing proteins and their partners (e.g., subunits, upstream proteins). A review of the evidence supporting this hypothesis is presented. Also, parallels between the mechanisms underlying a functional iron-deficient state in Alzheimer disease and those occurring for chlorosis in plants are discussed. Finally, a model describing the generation of a functional iron deficiency in Alzheimer disease is put forward.

BENEFITS OF THE EFFICACY AND SAFETY OF VITAMIN AND MINERAL COMPLEX "VITRUM PRENATAL FORTE" IN THE PREVENTION OF HYPOVITAMINOSIS AND MINERAL DEFICIENCY IN PREGNANCY

Non-interventional (observational) studies, which are of great medical and social importance, are one of the methods to assess the effectiveness and safety of pharmaceutical products in routine clinical practice, to clarify the risk profile and benefits of certain therapies. The aim of this study was to evaluate the efficacy and safety of vitamin and mineral complex "Vitrum Prenatal Forte" in the prevention of hypovitaminosis and mineral deficiency in pregnancy to improve maternal and perinatal outcomes. One of the important aims of the large-scale study was to evaluate the efficacy of the drug Vitrum Prenatal Forte in the prevention and treatment of anaemia in pregnant women. This article reviews the epidemiology of iron deficiency, features of iron metabolism, etiology and pathogenesis of iron deficiency in pregnant women and maternity women, approaches to the diagnosis of iron deficiency anaemia and iron deficiency, methods of prevention and treatment of iron deficiency states.

Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum.

Cadmium (Cd) is an environmental pollutant that damages various tissues. Cd may cause a depletion of iron stores and subsequently an iron deficiency state in the liver. However, the molecular mechanism of decreased iron accumulation in the liver induced by long-term exposure to Cd is unknown. In this study, we investigated the hepatic accumulation of iron and the proximal duodenal expression of the genes involved in iron transport using mice chronically exposed to Cd. Five-week-old female C57BL/6J mice were fed a diet containing 300 ppm Cd for 12, 15, 19 and 21 months. The iron concentration in the liver was markedly decreased by Cd. Among iron-transport-related genes in the proximal duodenum, the gene expression of HCP1 and Cybrd1 was significantly decreased by Cd. HCP1 is an influx transporter of heme iron. Cybrd1 is a reductase that allows non-heme iron to enter cells. The expression of iron-transport-related genes on the duodenal basolateral membrane side was hardly altered by Cd. These results suggest that long-term exposure to Cd suppresses the expression of HCP1 and Cybrd1 in the proximal duodenum, resulting in reduced iron absorption and iron accumulation in the liver.

The Role of Fractalkine in the Regulation of Endometrial Iron Metabolism in Iron Deficiency.

Iron is a crucial element in the human body. Endometrial iron metabolism is implicated in endometrium receptivity and embryo implantation. Disturbances of the maternal as well as the endometrial iron homeostasis, such as iron deficiency, can contribute to the reduced development of the fetus and could cause an increased risk of adverse pregnancy outcomes. Fractalkine is a unique chemokine that plays a role in the communication between the mother and the fetus. It has been demonstrated that FKN is involved in the development of endometrial receptivity and embryo implantation, and it functions as a regulator of iron metabolism. In the present study, we examined the effect of FKN on the iron metabolism of HEC-1A endometrial cells in a state of iron deficiency mediated by desferrioxamine treatment. Based on the findings, FKN enhances the expression of iron metabolism-related genes in iron deficiency and modifies the iron uptake via transferrin receptor 1 and divalent metal transporter-1, and iron release via ferroportin. FKN can activate the release of iron from heme-containing proteins by elevating the level of heme oxygenase-1, contributing to the redistribution of intracellular iron content. It was revealed that the endometrium cells express both mitoferrin-1 and 2 and that their levels are not dependent on the iron availability of the cells. FKN may also contribute to maintaining mitochondrial iron homeostasis. FKN can improve the deteriorating effect of iron deficiency in HEC-1A endometrium cells, which may contribute to the development of receptivity and/or provide iron delivery towards the embryo.

Frequency of Serum Ferritin Level in Non-Anemic Pregnant Women Presenting at Hospital

Objective: To determine mean serum ferritin level in non-anemic pregnant women presenting at Isra University Hospital during their antenatal visit. Study Design: Cross sectional study. Place and Duration: Department of Obstetrics and Gynecology at Isra University Hospital Hyderabad. January 2019-Jun 2019 Methods: A total of 78 non-anemic pregnant women with hemoglobin level&gt;11gm/dl during 1st and 3rd trimester and&gt;10.5gm/dl during 2nd trimester (as defined by CDC Criteria for anemia) were included in this study. A detailed history was obtained. All variable information was recorded in predesigned Performa. Results: The average age of women was 30.15±3.36 years. Mean serum ferritin level in non-anemic pregnant women was 13.05±5.088 nm/dl. Out of 78 cases 43(55.1%) of non-anemic female were found to have Iron deficiency state on the basis of serum ferritin estimates ≤12 ng/ml. Conclusion: In pregnancy, plasma volume, erythropoesis, and fetoplacental unit demand rise, causing iron defficiency. All pregnant women should be tested for iron status. Proper ID surveillance among pregnant women ensures accurate recording, assessment, and introduction of serum ferritin test early in the first trimester with the first ANC visit to catch afflicted pregnant. Keywords: serum ferritin, Non-anemic pregnant women, Iron deficiency anemia