Nutritional Iron Deficiency Research Articles

The Effect of Iron Therapy on Plasma Ghrelin and Leptin Levels in Egyptian Children with Iron Deficiency Anemia

Abstract Background Iron deficiency (ID) is the most common micronutrient deficiency and the most common cause of anemia worldwide. It is known that iron deficiency anemia effects appetite and growth negatively. The aim of this study was to investigate the effect of iron therapy on appetite and plasma ghrelin and leptin levels in children with nutritional iron deficiency anemia. Methods A prospective interventional study was done on 40 iron deficient pediatric patients diagnosed by CBC and Iron profile aged between 12 to 60 months. All 40 cases were given oral iron therapy (5mg/kg). Anthropometric measures and appetite score subjectively by mother were done before and after iron therapy. Caloric intake was calculated specially protein, Fat and CHO before and after treatment. Serum Ghrelin and Leptin done by ELISA Kit ;Specimen Collected whether Serum or plasma. Results The median rang (IQR) plasma ghrelin level was 1 (0.9 - 1.25) mg/mL before therapy and it increased to 3.6 (2.65 – 4.8) mg/mL (p < 0.001) while the median plasma leptin level decreased from 2.05 (1.4 – 3.2) ng/mL to 0.41 (0.3 – 0.65) ng/mL (p < 0.01) after therapy. The amount of daily caloric intake, carbohydrate and protein intake were significantly increased after therapy (p < 0.001). Body weight was correlated with plasma ghrelin levels before and after therapy significantly. There was a positive correlation for Ghrelin with TIBC and UIBC (r = 0.387, p-value = 0.014) (r = 0.388, p-value = 0.033) respectively. Conclusions In conclusion, the findings of our study indicate that plasma ghrelin level increases and leptin level decreases in children with iron deficiency anemia after iron therapy. The increase in appetite and improvement of growth in iron deficiency anemia might result from decreased leptin and increased plasma ghrelin levels after treatment.

Gambaran Kepatuhan Ibu Hamil dalam Mengonsumsi Tablet Fe Terhadap Kejadian Anemia di Wilayah Kerja Puskesmas Sadananya

Anemia is a concerning condition for pregnant women. The World Health Organization (WHO) reports that the prevalence of anemia among pregnant women is around 35-37%, and this increases with the progression of pregnancy. Nutritional iron deficiency anemia tends to be more prevalent in developing countries than in developed ones. The incidence rate of anemia in Ciamis Regency, based on the health profile of the regency, is 20.05%. This study aims to depict the compliance of pregnant mothers in consuming iron (Fe) tablets concerning the occurrence of anemia in the working area of Sadananya Community Health Center in 2020. The research design employed in this study is descriptive research. The population consists of all pregnant mothers with anemia during pregnancy in the working area of Sadananya Community Health Center, Ciamis Regency, amounting to 723 individuals in the year 2020. Cluster Sampling technique was used for sample selection. The analysis conducted in this study is univariate. The research results revealed that almost all respondents, totaling 67 individuals (84.4%), were non-compliant in consuming Fe tablets, whereas a small portion of respondents, totaling 12 individuals (15.2%), exhibited compliance in consuming Fe tablets. In conclusion, the majority of respondents, 67 individuals (84.8%), were non-compliant in consuming Fe tablets. It is recommended that relevant institutions, particularly Sadananya Community Health Center, become more proactive in providing education to pregnant women about pregnancy-related anemia and the importance of consuming Fe tablets.

Dietary iron deficiency impairs effector function of memory T cells following influenza infection.

The establishment of memory T cell responses is critical to protection against pathogens and is influenced by the conditions under which memory formation occurs. Iron is an essential micronutrient for multiple immunologic processes and nutritional deficiency is a common problem worldwide. Despite its prevalence, the impact of nutritional iron deficiency on the establishment of memory T cell responses is not fully understood. In this study we investigate the impact of nutritional iron deficiency on the generation, phenotype, and function of memory T cell responses using a murine model of dietary iron modulation in the context of influenza infection. Iron deficient mice have decreased systemic iron levels and develop significant anemia. Increased T cell expression of the transferrin receptor (CD71) is seen in iron deficient mice at baseline. During primary influenza infection, iron deficient mice experience increased weight loss and phenotypic evidence of impairments in T cell activation. Following recovery from infection, iron deficient mice generate increased influenza specific memory T cells which exhibit impaired ability to produce IFNγ, most notably within the lung. Importantly, the ability to produce IFNγ and TNFα is not recovered by co-culture with iron replete dendritic cells, suggesting a T cell intrinsic alteration in functional memory formation. Altogether, these results isolate a critical effect of nutritional iron deficiency on T cell memory development and function.

Retracted: Changes of Serum Ferritin, Hemoglobin, and Serum Iron (SI) and Treatment Effect of Iron Proteinsuccinylate Oral Solution Combined with Vitamin A and D Drops on Children with Nutritional Iron Deficiency Anemia.

[This retracts the article DOI: 10.1155/2022/2972617.].

A case report on the use of Ayurveda in the treatment of Iron Deficiency Anaemia

Among pregnant women and young children, nutritional iron deficiency anaemia is a worldwide public health concern and the leading cause of anaemia. Iron deficiency anaemia is often caused by blood loss or mal-absorption. Iron deficiency anaemia and Pandu Roga are very similar clinical entities. Pitta Pradhan Vyadhi is Pandu Roga. The vitiated Doshas in Pandu Roga cause a disruption in tissue metabolism, which results in Dhatu-Shathilya in all of Dhatu. Paleness is the dominant colour across the body. The Rasavaha and Raktavaha Srotasas play a significant role in the development of Pandu. In this case study, we see a 22-year-old female patient with iron deficiency anaemia who, after a month of treatment with Ayurvedic formulations in the Pandu Roga line of treatment and iron-rich dietary supplements, experienced a dramatic improvement in her symptoms (less swelling, no pallor, increased energy, decreased palpitation, and hair loss of 10 strands per day) and an increase in her haemoglobin level (from 8.6g/dl to 12.7g/dl) at a very rapid pace. The Samprapti of Pandu Roga may be broken with the aid of the formulas. Iron deficiency anaemia (Pandu) may be effectively treated with Ayurvedic medication.

Diagnostic Utility of Bone Marrow Aspiration Cytology- A Hospital Based Prospective Study at Nepalgunj Medical College

Introduction: Hematological disorders are common in all age groups and are worldwide in distribution. At times, routine hematological tests are not sufficient to diagnose blood disorders. Bone marrow examination serves as an important diagnostic aid to evaluate various neoplastic and non-neoplastic hematological diseases.
 Aims: To study role of Bone Marrow Aspiration Cytology in diagnosing hematological disorders. 
 Methods: This is a one-year hospital based prospective study done at Department of Pathology, NGMC, Kohalpur. It included 34 cases subjected to Bone marrow aspiration cytology. Correlation with Peripheral Blood Smear, Reticulocyte count, pearls iron stain and other parameters were done before giving the final diagnosis.
 Results: Age of patients ranged from 10-82 years with equal gender distribution. Common indications for Bone marrow examination were pancytopenia (50%), followed by Anemia and Thrombocytopenia. Megaloblastic Anemia (n=10,29%) was the commonest Anemia followed by mixed nutritional deficiency and Iron Deficiency Anemia. Hematological Malignancy accounted for six cases, of which Acute Myeloid Leukemia was diagnosed in two cases. Infectious causes comprised of two cases of Visceral Leishmaniasis and one case of Bone Marrow Tuberculosis.
 Conclusion: Bone marrow aspiration cytology serves as an important adjunct in diagnosing hematological disorders. More reproducible results are obtained if bone marrow biopsy is done in conjucntion with aspiration cytology.

Brain iron acquisition depends on age and sex in iron-deficient mice.

Adequate and timely delivery of iron is essential for brain development. The uptake of transferrin-bound (Tf) iron into the brain peaks at the time of myelination, whereas the recently discovered H-ferritin (FTH1) transport of iron into the brain continues to increase beyond the peak in myelination. Here, we interrogate the impact of dietary iron deficiency (ID) on the uptake of FTH1- and Tf-bound iron. In the present study, we used C57BL/6J male and female mice at a developing (post-natal day (PND) 15) and adult age (PND 85). In developing mice, ID results in increased iron delivery from both FTH1 and Tf for both males and females. The amount of iron uptake from FTH1 was higher than the Tf and this difference between the iron delivery was much greater in females. In contrast, in the adult model, ID was associated with increased brain iron uptake by both FTH1 and Tf but only in the males. There was no increased uptake from either protein in the females. Moreover, transferrin receptor expression on the microvasculature as well as whole brain iron, and H and L ferritin levels revealed the male brains became iron deficient but not the female brains. Last, under normal dietary conditions, 55 Fe uptake was higher in the developing group from both delivery proteins than in the adult group. These results indicate that there are differences in iron acquisition between the developing and adult brain for FTH1 and Tf during nutritional ID and demonstrate a level of regulation of brain iron uptake that is age and sex-dependent.

The treatment of chronic anemia in heart failure: a global approach.

Chronic anemia is an independent risk factor for mortality in patients with heart failure (HF). Restoring physiological hemoglobin (Hb) levels is essential to increase oxygen transport capacity to tissues and improve cell metabolism as well as physical and cardiac performance. Nutritional deficits and iron deficiency are the major causes of chronic anemia, but other etiologies include chronic kidney disease, inflammatory processes, and unexplained anemia. Hormonal therapy, including erythropoietin (EPO) and anabolic treatment in chronic anemia HF patients, may contribute to improving Hb levels and clinical outcomes. Although preliminary studies showed a beneficial effect of EPO therapy on cardiac efficiency and in HF, more recent studies have not confirmed this positive impact of EPO, alluding to its side effect profile. Physical exercise significantly increases Hb levels and the response of anemia to treatment. In malnourished patients and chronic inflammatory processes, low levels of anabolic hormones, such as testosterone and insulin-like growth factor-1, contribute to the development of chronic anemia. This paper aims to review the effect of nutrition, EPO, anabolic hormones, standard HF treatments, and exercise as regulatory mechanisms of chronic anemia and their cardiovascular consequences in patients with HF.

Bone marrow iron scoring in healthy and clinically ill dogs with and without evidence of iron‐restricted erythropoiesis

There are few reports in dogs that have evaluated the utility of semi-quantitative scoring of bone marrow iron stores in conjunction with reticulocyte hemoglobin (CHr) to identify iron-restricted erythropoiesis due to absolute iron deficiency or iron sequestration. An established system for scoring iron stores in human bone marrow samples was applied to dogs. The objectives were to evaluate interobserver agreement (Κω ), determine marrow iron scores in dogs without detectable hematologic abnormalities, and assess combined interpretation of iron scores and CHr to evaluate for iron-restricted erythropoiesis. Four blinded observers independently scored iron in 139 Prussian blue-stained canine marrow samples from 0 (none) to 6 (very heavy), including healthy controls (n = 12), clinically ill dogs with (n = 100) and without (n = 16) detectable hematologic abnormalities, and dogs with experimental nutritional iron deficiency (n = 11). Additional medical record data were available for 118 dogs to evaluate for other evidence of iron deficiency (abnormal CHr, RBC indices, serum iron variables, external blood loss, or nutritional deficiencies). Mean Κω was 0.69 (substantial agreement) for all samples but was 0.44 (moderate agreement) for samples with iron scores <3, indicating distinguishing scores 0-2 may not be reliable. Dogs without detectable hematologic abnormalities had scores from 3-5. Dogs with scores <3 and decreased CHr often had more indicators of iron deficiency vs dogs only having low iron scores or low CHr. Evaluation of dogs with marrow iron score <3 for external blood loss or nutritional deficiencies is likely clinically worthwhile, particularly if there is also decreased CHr.

Study of prevalence of anaemia and haematological parameters in children below 12 years in Northern Karnataka

Anaemia may be defined as a reduction in red blood cell (RBC) mass or blood haemoglobin (HGB) concentration. The most common cause of anaemia in newborns include blood loss, Rh or ABO incompatibility in 3 to 6 months suggests hemoglobinopathy, Nutritional iron deficiency causes after six months hence symptoms of blood examination in children play a significant role below 12 years. 92 children below 12 years of age having anaemia were studied. The blood examination was done to rule out PCV, MCV, MCH, MCHC, RPW, Hb%, PS study, reticulocyte count, and serum iron (Fe), Serum B, folic acids. The types of anaemia were 53(57.6%) anaemia, 13(14.1%) Thalassemia, 10(10.8%) Megablastic anaemia, 8(8.6%) Anaemia of acute haemorrhage, 5(5.4%) sickle cell anaemia, 2(2.1%) aplastic anaemia, 1(1.08%) leukaemia. Clinical manifestations had 92(100%) pallor, 78(84.7%) weakness and fatigability, 36(39.1%) fever, 26(28.2%) Icterus, 19(20.6%) shortness of breathing, 16(17.3%) hepatomegaly, 14(15.2%) cough, 13(14.1%) history of pica, 12(13%) splenomegaly, 10(10.8%) petechiae, 9(9.7%) vomiting, 9(9.7%) Koilonychias, 5(5.4%) hyper-pigmentation, 6(6.5%) tremors, 21(22.8%) was mild anaemia, 42(45.6%) moderate, 29(31.5%) severe anaemia on the basis of haemoglobin level. This pragmatic study of anemia had iron deficiency was a major cause followed by thalassemia, megaloblastic, acute hemorrhagic sickle cell, aplastic anemia. This study will be helpful to the pediatrician to treat such children efficiently to avoid morbidity and mortality.

Severe iron deficiency anemia with critically low hemoglobin in a 2-year-old child: a case report

Background: Anemia in young children is a major public health problem worldwide. Around 1.6 million people have been diagnosed with anemia, and 47.4% of them are preschool children. Nutritional Iron Deficiency Anemia (IDA) is the most common type of anemia in pediatrics. Several complications happen due to IDA during the first 2 years of life, such as reducing cognitive development, lowering immunity, and delaying growth. Case Presentation: A 2-year-old girl was brought to the Emergency Room complaining of fever (39&amp;#xb0;C) associated with skin pallor for 2 months. A complete blood count laboratory test result showed a very critical low hemoglobin (Hb) 3.39 g/dL. She received a blood transfusion, as a life-saving treatment. She was diagnosed with IDA secondary to formula milk dependency. Her Hb reached 10.62 g/dL and she was discharged with iron supplementation for 6 months. Conclusion: This case adds more to the literature by documenting critically low Hb level with positive findings in physical examination, which are pansystolic murmur and palpable bounding pulse, indicating severe IDA.

Management of nutritional iron deficiency anemia for young children in the emergency department.

Guidelines for young children with nutritional iron deficiency anemia (IDA) presenting to the emergency department (ED) are lacking, leading to variability in care. We aimed to standardize management of these patients through the development and implementation of an evidence-based algorithm using quality improvement methodology. Baseline data of the target population (n=42; 60% male; median age 22.5 months, median hemoglobin 5.3g/dl) identified variability across four key measures of clinical management: laboratory evaluation, therapy choice, therapy administration, and patient disposition. Literature review and consensus from pediatric hematology providers informed a draft algorithm that was refined in an iterative multidisciplinary process. From September 2020 to June 2021, we aimed to increase IDA management per the algorithm by ≥20% relative to baseline for the four key outcome measures using sequential Plan-Do-Study-Act (PDSA) cycles. Process measures focusing on provider communication/documentation and balancing measures involving efficiency and therapy-related adverse events were assessed concurrently. Thirty-five patients were evaluated among four PDSA cycles and shared similar characteristics as the baseline population. Improvements of ≥20% above baseline adherence levels or 100% adherence were achieved for all outcome measure across four PDSA cycles. Adherence to recommended laboratory evaluation improved from 43 (baseline) to 71%, therapy choice from 78 to 100%, therapy administration from 50 to 83%, and disposition from 85 to 100%. ED length of stay remained stable. Implementation of a standardized algorithm for young children with nutritional IDA in the ED increased adherence to evidence-based patient care.

Iron Deficiency Anemia in Pregnancy.

Through its functions in oxygen delivery, electron transport, and enzymatic activity, iron is crucial for the operation of all cells. High metabolic rate cells need more iron and are more likely to malfunction when there is an iron deficit. Since the mother's blood volume expands during pregnancy, and the fetus grows and develops, there is a sharp increase in the need for iron. Negative pregnancy outcomes, such as increased maternal sickness, low birthweight, preterm, and intrauterine growth restriction, are linked to iron deficiency. IDA, or nutritional iron deficiency anemia, affects more than two billion people worldwide and is the most prevalent disease. Based on the regression-based analysis, the prevalence of anemia in the World Health Organization's global database was calculated to be 14%. According to recent data, there are 17.4% more IDA cases among pregnant women in industrialized countries than in poor ones (up to 56% more cases). Despite the fact that oral iron supplementation is frequently used to treat IDA, not all patients benefit from oral iron therapy. This is caused by a number of things, which include the adverse effects of oral iron, resulting in low compliance and ineffectiveness. In a sizable group of patients taking oral iron preparations, the adverse effects primarily include GI symptoms. Intravenous iron was previously underutilized since it was linked to unfavorable and occasionally dangerous side effects. New type II and III iron complexes have been created recently, though, and they offer superior compliance and toleration in addition to strong efficacy and a good safety profile.

Maternal nutritional awareness and iron deficiency anemia in children aged 6 months–2 years in a tertiary care hospital in Coimbatore, Tamil Nadu

Objective: This study aims to analyze the risk factors and vital role of mothers in prevention of nutritional anemia in the early childhood. Methods: A hospital-based cross-sectional study done in Coimbatore for 2 years. Using a pre-tested structured validated tool, mothers of children aged 6 months–2 years were interviewed to collect information on factors contributing to anemia with special regard to maternal knowledge. Results: Anemia was more in the latter half of infancy (67.2%) with male predominance (60.5%). An affirmative association between increased cow’s milk intake and low hemoglobin was present (p=0.002). Employed and less educated mothers had more anemic children (p&lt;0.05). Of 16% mothers classified as “poor” awareness, 95.45% children had low hemoglobin (p&lt;0.05). Conclusion: Recognizing the causative factors plays an essential role in preventing iron deficiency anemia (IDA). Exclusive breastfeeding must be promoted, along with avoiding excessive cow’s milk intake. Intervening at the right period with age-appropriate foods becomes a necessity. Maternal illiteracy has a positive correlation with anemia in infants. Improving maternal awareness by the physicians will pave the road toward a nation free from anemia.

Ayurveda in Management of Iron Deficiency Anemia: A Case Report

Nutritional iron deficiency anemia is the most common cause of anemia and a global public health problem among young children and pregnant women. Blood loss, malabsorption is the common cause of iron deficiency anemia. Pandu roga is a clinical entity with great resemblance to iron deficiency anemia. Pandu roga is Pitta pradhan vyadhi. In Pandu roga tissue metabolism gets affected due to vitiated Doshas which in turn into Dhatu- shyathilya in all Dhatu. There is a predominance of paleness all over the body. Rasavaha and Raktavahasrotasas are chiefly involved in the pathogenesis of Pandu. So, here is a case report of 21 years old female patient with iron deficiency anemia who was given Ayurvedic formulations in the line of treatment of Pandu roga along with dietary supplements rich in iron for a period of one month and marked improvement in symptoms (i.e., swelling was reduced, pallor absent, she was feeling energetic, hair fall (10 strands/day), palpitation had also decreased) with increase in hemoglobin level (i.e., from 8.6g/dl to 12.7g/dl) in a very short duration of time. The formulations help in breaking the Samprapti of Pandu roga. This shows the efficacy of Ayurvedic medicine in the treatment of iron deficiency anemia (Pandu).

The Articulate Canker-Aphthous Ulcer

Aphthous ulcer occurs as a frequent, idiopathic, painful, singular, multiple or reoccurring oral ulceration. Of obscure aetiology, oral trauma, stress, anxiety, diverse systemic diseases as coeliac disease, Crohn’s disease, Behçet’s syndrome, reactive arthritis or infection with human immune deficiency virus (HIV), drugs such NSAIDs, β-blockers, angiotensin converting enzyme (ACE) inhibitors, deficiencies of vitamins and trace elements as zinc, iron, B12, folate or sensitivity to food and chemicals may engender the ulcer. Contingent to magnitude, aphthous ulcer is subcategorized into minor ulcer, major ulcer or herpetiform ulcer. Aphthous ulcer manifests upon non-keratinized oral mucosa as a well circumscribed, centric, necrotic ulcer circumscribed by a grey, fibrinous exudate and an erythematous halo. The ulcer requires a segregation from contact dermatitis, lichen planus, oral carcinoma, infection with herpes simplex virus (HSV), various drug induced lesions or autoimmune diseases. Aphthous ulcer can be evaluated with clinical examination, complete blood count with nutritional deficiencies of iron, folate or vitamin B12, neutropenia, serum anti-endomysial antibodies and transglutaminase (tTg-IgA) for coeliac disease and investigations for HIV. Cogent therapeutic options are local anaesthetics, coating or occlusive agents as bismuth subsalicylate, sucralfate, 2-octyl cyanoacrylate, bio-adherent emollient pastes, oral antiseptics as chlorhexidine gluconate, hydrogen peroxide, antiinflammatory agents as glucocorticoids, metalloprotease inhibitors, antimicrobials as tetracycline, doxycycline, minocycline, honey, immunomodulatory agents as amlexanox, colchicine, cyclosporine, cyclophosphamide, dapsone, methotrexate, montelukast, thalidomide or retinoids.

Effect of Lacticaseibacillus casei Zhang on iron status, immunity, and gut microbiota of mice fed with low-iron diet

• The low-iron diet significantly changed the structure of the gut microbiota and reduced bacterial diversity. • LCZ supplementation significantly reduced serum IL-18 level, a pro-inflammatory cytokine. • LCZ mitigated serum total iron binding capacity (TIBC) level elevation induced by the low-iron diet in mice. Nutritional iron deficiency is a common health problem. In this study, the fecal metagenomes, serum cytokine profiles, and iron status of four mouse groups (n = 8 per group), i.e., CT (control diet), LI (low-iron diet), CTL (control diet with Lacticaseibacillus casei Zhang, LCZ), and LIL (LI with LCZ) were compared after dietary intervention. Significant differences were observed in the fecal microbiota diversity and structure between groups at week 8, with diminished microbial diversity in the LI group. LCZ supplementation could regulate the microbiota diversity. The pro-inflammatory cytokine IL-18 significantly increased in mice received low-iron diet compared with those in the probiotic group (low-iron diet), suggesting LCZ possibly exerted anti-inflammatory effect on the low-iron diet mice. Additionally, LCZ supplementation decreased the serum total iron binding capacity (TIBC) level in mice ( P < 0.05). Altogether, our data showed that LCZ supplementation partially protected mice given low-iron diet from gut dysbiosis and improved their iron status.

Changes of Serum Ferritin, Hemoglobin, and Serum Iron (SI) and Treatment Effect of Iron Proteinsuccinylate Oral Solution Combined with Vitamin A and D Drops on Children with Nutritional Iron Deficiency Anemia.

Objective The purpose was to evaluate the treatment effect of iron proteinsuccinylate oral solution combined with vitamin A and D drops on children with nutritional iron deficiency anemia. Methods 124 children treated in the outpatient department of our hospital from January 2017 to January 2020 were selected as the study subjects. They were randomly divided into control and observation two groups. The control group was treated with iron proteinsuccinylate oral solution (1.5 mL/kg) in the morning and evening, respectively. The observation group received adjuvant treatment with oral vitamin A and D drops based on the treatment of the control group. The treatment effect of proteinsuccinylate oral solution combined with vitamin A and D drops was evaluated by the serum iron (SI), serum ferritin (SF), and transferrin (TRF) levels, the values of CD3+, CD4+, and CD4+/CD8+, and other evaluation indicators. Results After treatment, the SI and SF levels of children in both groups significantly increased (P < 0.01) while the TRF level significantly decreased (P < 0.01), and the SI and SF levels in the observation group increased more significantly, and the TRF level decreased more significantly compared with those in the control group (P < 0.01). After treatment, the values of CD3+, CD4+, and CD4+/CD8+ of children in both groups significantly increased compared with those before treatment (P < 0.01), and the values of CD3+, CD4+, and CD4+/CD8+ increased more significantly in the observation group compared with those in the control group (P < 0.01). In addition, the evaluation results of treatment effect showed that the markedly effective rate in the observation group was significantly higher than that in the control group (P < 0.01). Conclusion Iron proteinsuccinylate oral solution combined with vitamin A and D drops can better improve the anemia symptoms in children, with high application value.

Sterol Composition Modulates the Response of Saccharomyces cerevisiae to Iron Deficiency.

Iron is a vital micronutrient that functions as an essential cofactor in multiple biological processes, including oxygen transport, cellular respiration, and metabolic pathways, such as sterol biosynthesis. However, its low bioavailability at physiological pH frequently leads to nutritional iron deficiency. The yeast Saccharomyces cerevisiae is extensively used to study iron and lipid metabolisms, as well as in multiple biotechnological applications. Despite iron being indispensable for yeast ergosterol biosynthesis and growth, little is known about their interconnections. Here, we used lipid composition analyses to determine that changes in the pattern of sterols impair the response to iron deprivation of yeast cells. Yeast mutants defective in ergosterol biosynthesis display defects in the transcriptional activation of the iron-acquisition machinery and growth defects in iron-depleted conditions. The transcriptional activation function of the iron-sensing Aft1 factor is interrupted due to its mislocalization to the vacuole. These data uncover novel links between iron and sterol metabolisms that need to be considered when producing yeast-derived foods or when treating fungal infections with drugs that target the ergosterol biosynthesis pathway.

Inflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)-New Aspects.

The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways have been proposed. A better understanding of the pathophysiology is warranted for developing novel therapeutic strategies. Here, we summarize recent evidence from experiments using animal models of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facet of diabetic neuropathy. Our experimental data suggest that these mild inflammatory processes are a likely common terminal pathway in diabetic neuropathy associated with the degeneration of intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-iron content, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammation and fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mild inflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to trigger mild inflammation of peripheral nerves, associated with neuropathy even in the absence of overt diabetes mellitus. Our finding may be the experimental analog of recent observations identifying systemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model of type 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulin treatment causing an abrupt reduction in HbA1c. This is in line with observations in patients with severe diabetes developing a small fiber neuropathy upon treatment-induced rapid HbA1c reduction. If the inflammatory pathogenesis could be further substantiated by data from human tissues and intervention studies, anti-inflammatory compounds with different modes of action may become candidates for the treatment or prevention of diabetic neuropathy.