Iron Transferrin Research Articles

DIAGNOSTIC AND PROGNOSTIC VALUE OF IRON METABOLISM PARAMETERS IN PATIENTS WITH SPONTANEOUS SUPRATENTORIAL INTRACEREBRAL HAEMORRHAGE IN ACUTE PERIOD

The aim of the study is to investigate the diagnostic and prognostic value of integrated assessment of iron metabolism parameters in patients with spontaneous supratentorial intracerebral haemorrhage in acute period. Materials and methods. This prospective cohort study included 88 patients with spontaneous supratentorial intracerebral haemorrhage during the course of conservative treatment. Diagnosis was made based on the findings of clinical and neuro-imaging investigations. On the 1st day of the hospital admission fasting blood samples were taken. Levels of ferritin, hepcidin, iron, total iron binding capacity, unsaturated iron binding capacity and transferrin saturation were detected. Early neurological deterioration and unfavourable outcome of acute period of spontaneous supratentorial intracerebral haemorrhage as grading 4-6 scores by modified Rankin scale on the 21st day of the disease were chosen as clinical endpoints. Lethal outcome and unfavourable functional outcome were also recorded. Results. Three profile types of evaluated iron metabolism parameters were identified based on the cluster analysis in the patients with intracerebral haemorrhage. It has been found out the profile types with initial higher levels of serum hepcidin and ferritin in blood together with lower serum iron concentration (type II and particularly type III) are associated with more severe cerebral structures damage and increased risk of early clinical deterioration (relative risk (95% confidence interval) = 6,01 (1,54–24,86), р=0,0120) and unfavourable functional outcome of the disease (relative risk (95% confidence interval) = 4,45 (2,25–8,80), р˂0,0001). Conclusion. Profile type of serum hepcidin, ferritin and iron concentrations together with transferrin saturation in the patients with spontaneous supratentorial intracerebral haemorrhage on the 1st day of hospital admission is the informative integrated marker for short-term prognosis during the course of conservative treatment.

Localization and Kinetics of the Transferrin-Dependent Iron Transport Machinery in the Mouse Placenta.

ABSTRACTThe placenta transports iron to the fetus to support growth and development. Mice are commonly used to study placental iron transport. The subcellular locations of transferrin receptor and ferroportin 1 in iron-transporting cells in the mouse placenta have not been directly assessed. Using immunogold electron microscopy, we determined that transferrin receptor is concentrated on the intracellular vesicles in syncytiotrophoblast I while ferroportin 1 is on the basal membrane of syncytiotrophoblast II. Fluorescent imaging of maternally injected transferrin iron in the placentas collected at 6 time points postinjection (n = 1–3 animals/time point) showed that transferrin iron was taken up and metabolized within syncytiotrophoblast I within 48 h after injection. These data indicate that the intracellular iron-trafficking mechanism is distinct in different placental cells.

Vitamin D and iron status in children with food allergy

BackgroundChildren with food allergy are at specific risk for nutritional deficiencies. ObjectiveTo retrospectively determine prevalence of vitamin D and iron deficiencies in children with or without food allergy (FA). MethodsWe compared the markers of vitamin D and iron status of 0 to 17-year-olds with cow’s milk allergy (CMA) (n = 77), those with other FAs (n = 70), and those with atopy without FA (n = 87) at an academic pediatric allergy practice. Multiple linear regression analyses were performed to determine the impact of CMA and other FAs on vitamin D levels and iron markers. ResultsVitamin D deficiency was detected in one-fourth and insufficiency in one-third of children with CMA and other FAs and in those with atopic diseases but no FA, respectively. Vitamin D levels were associated with vitamin D supplementation and consumption of breast milk, cow’s milk, infant formula, or plant-based milk beverage, but not with CMA or other FAs. Older children with FA who did not consume any cow’s milk or alternative milk beverage were at highest risk for vitamin D insufficiency. Children with CMA have a higher rate of iron deficiency anemia (8%) than children with other FAs (1%) or those with no FA (5%, P < .001); however, suboptimal levels of transferrin saturation and iron were detected in up to one-third of children with CMA or other FAs. ConclusionVitamin D deficiency and insufficiency is common in children with atopy overall, but children with CMA are at higher risk for iron deficiency anemia. Intensive nutritional counseling and nutrient intake monitoring, specifically for vitamin D and iron in those avoiding cow’s milk, are necessary to optimize nutritional status.

Comparison of Clinical and Biochemical Parameters of Patients with Guillain Barre Syndrome and Myasthenia Gravis: Retrospective Single Center Experience

Background: Guillain-Barré syndrome (GBS) and Miyastenia gravis (MG) are common neurological autoimmune diseases. With this study, we aimed to compare the patients’ complaints, clinical course and laboratory parameters of both diseases. Methods: This study was carried out as a retrospective file scan. The study covers the dates between April 1, 2017, and April 20, 2020. The GBS and MG patients were compared in terms of sociodemographic characteristics, application complaints, clinical course, laboratory findings, treatments and outcomes. Results: In this study, 51 patients from both groups were included. The mean age of GBS and MG patients was 52.1 ±19.4 and 43.6 ±15.8 years, respectively. Respiratory involvement of the patients was 23.5% in GBS and 17.6% in MG. When the treatments of the patients were compared, it was observed that 78.4% of GBS patients and 98% of MG received IVIG treatments. Only two patients from GBS group were found to be ex. When the laboratory results were compared, it was found that lactate, vitamin D, transferrin and total iron binding capacity results were lower in GBS patients, whereas, vitamin B12 and ferritin results were lower in MG patients and this difference was statistically significant (p &lt;0.05). Conclusion: The clinical presentation of GBS and MG is diverse and the prognosis can vary significantly among patients. Within the scope of the data obtained from the study, it was concluded that wide anamnesis and laboratory analyzes are necessary and useful for the differential diagnosis of these two diseases.

Diabesity negatively affects transferrin saturation and iron status. The DICARIVA study

The relationship between iron status, obesity and type 2 diabetes mellitus (T2DM) has scarcely been tested. This study hypothesizes that patients with obesity and T2DM have altered iron metabolism. 537 T2DM patients were selected from the cross-sectional DICARIVA study excluding patients with high-sensitivity-C-reactive-protein (hs-CRP)≥ 10mg/L. Three groups according to body mass index (BMI) and waist perimeter (WP) were analysed: a) BMI<30kg/m2, non-high WP (n=105); b) BMI<30kg/m2, high WP (n=202); and c) diabesity, BMI≥ 30kg/m2, high WP (n=230). Group differences on cardiometabolic and iron status markers were tested. Women had significantly lower iron, ferritin, and transferrin saturation (TSAT) but higher transferrin and total iron binding capacity than men. Triglycerides/HDL-c ratio, as insulin-resistance (IR) marker, was higher in men while hs-CRP in women. TSAT was inversely related to BMI and hs-CRP. The diabesity group showed the highest hs-CRP (p<0.001) and IR (p<0.001) with the lowest TSAT (p=0.003). Low TSAT was highly prevalent in diabesity, mainly in women, suggesting that IR, inflammation, and abdominal adiposity alter iron transport and accumulation. The convenience of iron supplementation in diabesity patients with low TSAT should be urgently assessed, due the pro-oxidant effects of excess iron.

The Correlation between Serum Iron Level and Transferrin Saturation with Reticulocyte Hemoglobin Equivalent (RET-He) in Routine Hemodialysis

The Correlation between Serum Iron Level and Transferrin Saturation with Reticulocyte Hemoglobin Equivalent (RET-He) in Routine Hemodialysis

Ağır Demir Eksikliği olan Çocuk Hastalarda Vitamin D Düzeyi

Bu çalışmada ağır demir eksikliği anemisi olan çocuklarda Vitamin D eksikliği sıklığının belirlenmesi amaçlanmıştır. Bu çalışmaya 6-72 ay arasında ağır demir eksikliği anemisi olan 60 hasta ile benzer yaş ve cinsiyette 60 sağlıklı çocuk dahil edildi. Hasta grubuna kan hemoglobin düzeyi 7 g/dl'nin altında ağır demir eksikliği anemisi tanısı alan hastalar dahil edildi. Aneminin etiyolojisi ile ilgili olarak hasta grubundan hemogram, retikülosit sayımı, biyokimyasal analizler, serum demir ve demir bağlama kapasitesi, transferrin satürasyonu, ferritin, vitamin B12, folik asit ve serum Vitamin D düzeyleri için kan örneği alındı. Vitamin D eksikliği (<20 ng/mL) hasta grubunun %75'inde (n=45), kontrol grubunun %1.7'sinde (n=1) mevcuttu (p<0.001). Hasta grubunun Vitamin D düzeyi (16.2±13.3 ng/ml), kontrol grubuna (36.3±15.1 ng/ml) göre anlamlı olarak düşüktü (p<0.05). Kontrol grubunda gelişme geriliği olan çocuk bulunmazken, hasta grubunun %16.7'sinde gelişme geriliği vardı (p<0.001). Vitamin D eksikliği çok yüksek prevalansa sahiptir ve ağır demir eksikliği anemisi olan hastalarda Vitamin D düzeyi anlamlı olarak düşük bulunmuştur. Sonuç olarak, ciddi demir eksikliği anemisi olan hastalar Vitamin D eksikliği açısından değerlendirilmeli ve tedavi edilmelidir.

Abstract PO-147: Kidney iron overload in African American renal cancer patients with the ferroportin Q248H mutation

Abstract Iron plays a role in cellular replication, metabolism, and growth. Although iron is needed, the imbalance of iron in the body can result in adverse health effects, including cancer. Interestingly, cancer cells have frequently been observed to express increased levels or activity of proteins that are associated with iron metabolism. Ferroportin (FPN), the only known mammalian cell iron exporter, is essential for iron homeostasis. Germline mutations in FPN occur more frequently in African and African American populations. A glutamine to histidine amino acid substitution at position 248 (Q248H) is the first and most prevalent gain-of-function mutation observed in FPN, with an allele frequency range of 2.2% to 13.4% in African and African Americans. However, it is unknown whether FPN Q248H is involved in cancer-associated reprogramming of iron metabolism, especially in individuals of African descent where the FPN Q248H mutation is enriched. The Q248H mutation traditionally renders FPN resistant to degradation. As a result, iron release is increased and aberrant uptake of iron across epithelial barriers of tissues can occur to cause iron overload, a risk factor for cancer. We hypothesize that patients with FPN Q248H have improper regulation of iron and thus increased unbound iron that will result in subsequent systemic and kidney-specific iron overload. We leveraged the repository of kidney cancer patients and banked samples of the Urologic Oncology Branch at the NIH to determine the association of FPN Q248H with kidney cancer. In our study, Black males with kidney cancer that expressed FPN Q248H had earlier onset of cancer compared to those without the variant. There were higher iron levels (p&amp;lt;0.01) and transferrin saturation (p=0.01), a measure for blood iron transport, in serum form Black males with FPN Q248H compared to Black males without. Additionally, serum levels of the iron storage protein ferritin were elevated in association with FPN Q248H. In the kidney, both normal and tumor tissue had distinct levels of iron, as well as protein expression of ferritin and FPN between patients with and without FPN Q248H. In all, these results highlight a potential novel mechanism for global iron-associated cancer risk populations. This work will provide a foundation for future studies that include pre-cancer individuals and other cancer outcomes where the relationship between FPN Q248H and iron overload can be further examined to expand our knowledge of cancer risk. Citation Format: Samira Brooks, Cathy Vocke, Deliang Zhang, Victor Gordeuk, Tracey Rouault, Marston Linehan. Kidney iron overload in African American renal cancer patients with the ferroportin Q248H mutation [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-147.

Regulation of Iron Homeostasis through Parkin-Mediated Lactoferrin Ubiquitylation.

Somatic mutations that perturb Parkin ubiquitin ligase activity and the misregulation of iron homeostasis have both been linked to Parkinson's disease. Lactotransferrin (LTF) is a member of the family of transferrin iron binding proteins that regulate iron homeostasis, and increased levels of LTF and its receptor have been observed in neurodegenerative disorders like Parkinson's disease. Here, we report that Parkin binds to LTF and ubiquitylates LTF to influence iron homeostasis. Parkin-dependent ubiquitylation of LTF occurred most often on lysines (K) 182 and 649. Substitution of K182 or K649 with alanine (K182A or K649A, respectively) led to a decrease in the level of LTF ubiquitylation, and substitution at both sites led to a major decrease in the level of LTF ubiquitylation. Importantly, Parkin-mediated ubiquitylation of LTF was critical for regulating intracellular iron levels as overexpression of LTF ubiquitylation site point mutants (K649A or K182A/K649A) led to an increase in intracellular iron levels measured by ICP-MS/MS. Consistently, RNAi-mediated depletion of Parkin led to an increase in intracellular iron levels in contrast to overexpression of Parkin that led to a decrease in intracellular iron levels. Together, these results indicate that Parkin binds to and ubiquitylates LTF to regulate intracellular iron levels. These results expand our understanding of the cellular processes that are perturbed when Parkin activity is disrupted and more broadly the mechanisms that contribute to Parkinson's disease.

Genetic screens reveal CCDC115 as a modulator of erythroid iron and heme trafficking.

Transferrin-bound iron (TBI), the physiological circulating iron form, is acquired by cells through the transferrin receptor (TfR1) by endocytosis. In erythroid cells, most of the acquired iron is incorporated into heme in the mitochondria. Cellular trafficking of heme is indispensable for erythropoiesis and many other essential biological processes. Comprehensive elucidation of molecular pathways governing and regulating cellular iron acquisition and heme trafficking is required to better understand physiological and pathological processes affecting erythropoiesis. Here, we report the first genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens in human erythroid cells to identify determinants of iron and heme uptake, as well as heme-mediated erythroid differentiation. We identified several candidate modulators of TBI acquisition including TfR1, indicating that our approach effectively revealed players mechanistically relevant to the process. Interestingly, components of the endocytic pathway were also revealed as potential determinants of transferrin acquisition. We deciphered a role for the vacuolar-type H+ - ATPase (V- ATPase) assembly factor coiled-coil domain containing 115 (CCDC115) in TBI uptake and validated this role in CCDC115 deficient K562 cells. Our screen in hemin-treated cells revealed perturbations leading to cellular adaptation to heme, including those corresponding to trafficking mechanisms and transcription factors potentiating erythroid differentiation. Pathway analysis indicated that endocytosis and vesicle acidification are key processes for heme trafficking in erythroid precursors. Furthermore, we provided evidence that CCDC115, which we identified as required for TBI uptake, is also involved in cellular heme distribution. This work demonstrates a previously unappreciated common intersection in trafficking of transferrin iron and heme in the endocytic pathway of erythroid cells.

Transferrin Insufficiency and Iron Overload in Follicular Fluid Contribute to Oocyte Dysmaturity in Infertile Women With Advanced Endometriosis.

Purpose: To screen out specific protein with different concentration in follicular fluid from advanced endometriosis and determine its direct effect on mouse oocytes matured in vitro.Methods: FF samples were obtained from 25 patients (EMS group, n = 15; control group, n = 10) to screen the differential proteins by using iTRAQ Labeling and 2D LC-MS. Transferrin (TRF) in was found significantly decreased in EMS group, which was verified using ELISA in enlarged FF samples (EMS group, n = 31; control group, n = 27). The contents of ferric ion in FFs were detected by ELISA and TRF saturations were calculated in two groups. Germinal vesicle (GV) oocytes of mouse were maturated in vitro interfered with the FFs in five groups, whose concentrations of TRF were modulated, and maturation in vitro rates were compared among groups.Results: The reduced concentration of TRF with three analogs and increased concentration of ferric ion were found in the FF of the EMS group (p < 0.05). The numerical values of TSAT was 54.8% in EMS group, indicating iron overload in the FF. The EMS-FF showed significantly decreased maturation in vitro rate (p < 0.05) of mouse oocytes, which was improved with the supplementation of TRF, compared with the control-FF. The effect was blocked by the TRF antibody (p < 0.05).Conclusions: Being aware of the relatively small sample size, our results possibly suggest that TRF insufficiency and iron overload in FF from advanced EMS contribute to oocytes dysmaturity, which may be a cause of EMS-related infertility.

P0847HEPATIC ERYTHROPOIETIN SYNTHESIS IS ENHANCED IN HEMODIALYSIS PATIENTS WHO DO NOT REQUIRE ERYTHROPOIESIS-STIMULATING AGENTS

Abstract Background and Aims Erythropoietin is synthesized in the liver during the fetal period and mainly in the kidney after birth. However, some patients with end-stage chronic kidney disease do not require the administration of erythropoiesis-stimulating agents (ESA) despite their damaged renal function. This study aimed to clarify the origin of extrarenal erythropoietin generation in these patients. Method The origin of erythropoietin was investigated by analyzing the erythropoietin glycation patterns based on the percentages of migrated isoforms (PMI). Sera of stable hemodialysis (HD) patients with (ESA group) or without (non-ESA group) ESA treatment and umbilical cord blood of newborns (UCB group), which contained erythropoietin of liver origin, were analyzed. The non-ESA group was determined as HD patients without ESA treatment for &amp;gt; 6 months. Informed consent was obtained from all included HD patients and from the parents or guardians of the newborns. This study was performed with permission from the institutional ethical committee and was registered as a clinical trial (no. R000033462 UMIN000029335). Results The mean duration of no ESA treatment in the non-ESA group was 29.2 months. There were no differences in major clinical parameters, including age and HD duration. The hemoglobin concentration in the ESA group was 107 ± 5 g/L (mean ± standard error), which was significantly lower than that in the non-ESA group (123 ± 4 g/L) (P = 0.025, unpaired Student’s t-test). The PMI values of the ESA, non-ESA, and UCB groups were 12.6 ± 11.4％, 61.2 ± 13.1%, and 65.0 ± 13.5％, respectively, and the PMI value of the ESA group was significantly lower than that of non-ESA or UCB group (one-way analysis of variance with Tukey-Kramer test), suggesting that the glycation pattern of erythropoietin in the non-ESA group was similar to that in the UCB group but different from that in the ESA group. No significant differences were found in the reticulocyte ratio, serum iron concentration, total iron binding capacity, and ferritin and transferrin saturation between the ESA and non-ESA groups. Conclusion These results suggest that patients in the non-ESA group had enhanced extrarenal erythropoietin synthesis and that their erythropoietin originated from the liver. Further analysis of the underlying mechanism may contribute to the development of internal extrarenal erythropoietin-stimulating therapy.

Hypomorphic CAMKK2 in EA.hy926 endothelial cells causes abnormal transferrin trafficking, iron homeostasis and glucose metabolism

We recently reported that loss of calcium/calmodulin-dependent protein kinase kinase-2 (CAMKK2), a serine/threonine kinase activated by intracellular calcium, in mice leads to tissue-specific aberrant turnover of transferrin (TF), a receptor-mediated iron-transporter that supplies iron to tissues. Iron dyshomeostasis is associated with the pathogenesis of several diseases, making TF transport relevant to health. In this study, we used hemizygous CAMKK2 hypomorphic human endothelial cell (EA.hy926) clones to demonstrate that cells with reduced CAMKK2 exhibit increased TF uptake and transcytosis, and decreased intracellular trafficking to subcellular organelles compared to wild-type. The abnormal TF trafficking in CAMKK2 hypomorphic cells correlated with a reduction in intracellular iron content and defective glucose metabolism including glycolysis and mitochondrial respiration. CAMKK2 deficiency also caused reduction in GAPDH and VDAC1 protein level which correlated to defective bioenergetics function. These findings have identified a novel mechanistic link between abnormal calcium signaling, iron dyshomeostasis and metabolic dysfunction involving CAMKK2.

CAMKK2-CAMK4 signaling regulates transferrin trafficking, turnover, and iron\xa0homeostasis

BackgroundCirculatory iron is a hazardous biometal. Therefore, iron is transported in a redox-safe state by a serum glycoprotein - transferrin (TF). Different organs acquire iron from the systemic circulation through a tightly regulated mechanism at the blood-tissue interface which involves receptor-mediated internalization of TF. Thus, abnormal TF trafficking may lead to iron dyshomeostasis associated with several diseases including neurodegeneration. Iron -induced toxicity can cause neuronal damage to iron-sensitive brain regions. Recently, it was discovered that CAMKK2, a calcium (Ca2+)/calmodulin-activated kinase, controls receptor-mediated TF trafficking in mouse tissues, specifically in the brain. The biological function of CAMKK2 is mediated through multiple downstream effectors. Both CAMKK2 and one of its downstream kinase, CAMK4, exhibit overlapping expression in mouse brain. The role of CAMK4 in vesicular transport has been reported and loss of CAMKK2 or CAMK4 leads to cognitive defects in mouse. Therefore, it was hypothesized that CAMKK2-CAMK4 signaling regulates receptor-mediated TF trafficking and iron homeostasis which may be responsible for the neuronal malfunction observed in CAMKK2- or CAMK4-deficient mice.MethodsCAMK4−/− mouse was used to study tissue-specific turnover of TF, TF-receptor (TFRC) and iron. CRISPR/Cas9-based CAMKK2 and/or CAMK4 deleted human embryonic kidney-derived HEK293 cell clones were used to study the molecular defects in receptor-mediated TF trafficking. Further, a “zero functional G protein” condition in HEK293 cell was exploited to study CAMKK2-CAMK4 signaling-mediated regulation of intracellular Ca2+ homeostasis which was linked to calcium signaling during TF trafficking.ResultsLoss of CAMK4 leads to abnormal post-translational modifications (PTMs) and turnover of TF in mouse cerebellum and liver which was associated with iron dyshomeostasis in these tissues. The HEK293 cell-based study revealed that the absence of CAMKK2-CAMK4 signaling altered intracellular Ca2+ homeostasis and lead to abnormal calcium signaling during TF trafficking. Also, CAMKK2-CAMK4 signaling deficiency affected the molecular interaction of TF and TF-receptor-associated protein complexes which indicated a potential failure in the recruitment of interacting proteins due to differential PTMs in TF.ConclusionOverall, this study established a novel mechanistic link between intracellular Ca2+ level, receptor-mediated TF trafficking, and iron homeostasis, all regulated by CAMKK2-CAMK4 signaling.96jS1k-UhvBwj8b5MHadpoVideo Graphical abstract

Clinical Immunoassay for Human Hepcidin Predicts Iron Deficiency in First-Time Blood Donors.

Serum markers currently used as indicators of iron status have clinical limitations. Hepcidin, a key regulator of iron homeostasis, is reduced in iron deficiency (ID) and increased in iron overload. We describe the first CLIA-validated immunoassay with excellent accuracy and precision to quantify human serum hepcidin. Its diagnostic utility for detecting ID in first-time blood donors was demonstrated. A monoclonal competitive ELISA (C-ELISA) was developed for the quantitation of human hepcidin and validated according to CLIA guidelines. Sera from nonanemic first-time blood donors (n = 292) were analyzed for hepcidin, ferritin, transferrin, and serum iron. Logistic regression served to determine the utility of hepcidin as a predictor of ID. The C-ELISA was specific for human hepcidin and had a low limit of quantitation (4.0 ng/mL). The hepcidin concentration measured with the monoclonal C-ELISA was strongly correlated with a previously established, extensively tested polyclonal C-ELISA (Blood 2008;112:4292-7) (r = 0.95, P < 0.001). The area under the receiver operating characteristic curve for hepcidin as a predictor of ID, defined by 3 ferritin concentration thresholds, was >0.9. For predicting ID defined by ferritin <15 ng/mL, hepcidin <10 ng/mL yielded sensitivity of 93.1% and specificity of 85.5%, whereas the same hepcidin cutoff for ferritin <30 ng/mL yielded sensitivity of 67.6% and specificity of 91.7%. The clinical measurement of serum hepcidin concentrations was shown to be a potentially useful tool for diagnosing ID.

STUDY OF ELECTROLYTE DISORDERS AS CRITERION-IMPORTANT MARKERS OF ENDOGENOUS INTOXICATION IN PATIENTS WITH ANASTOMOSIS LEAKEGE AGAINST A BACKGROUND OF RESECTION OF THE SMALL INTESTINE

Summary. The aim of the study was to study the dependence of ion exchange and saturation with iron transferrin on the background of increasing endotoxicosis, depending on the severity of the clinical course of acute small bowel obstruction and peritonitis.&#x0D; Materials and methods. The research was carried out at the SI «ZIGUS NAMSU» and was based on the analysis of laboratory data of 63 patients with a failure of small intestinal anastomoses who in the future needed one of the options of resections of the segments of the small intestine, which were treated in the clinic from 2016 to 2019. All patients were divided into 3 groups according to the degree of physical severity of the condition on the APACHE II scale. The study was conducted in two stages: the first stage examined the content of zinc, copper and iron ions in the serum of all patients studied, the second stage of the study in patients evaluated the objective indicators of endogenous intoxication on the basis of leukocyte index of intoxication, index of content molecular weight, malonic aldehyde and diene conjugates in serum and iron levels in whole blood, as well as its serum.&#x0D; Results and Discussion. The study of Fe2+, Zn2+, Cu2+ metabolism in the serum of all patients with inflammatory phenomena of the peritoneum on the background of anastomosis failure revealed significant changes. In the clinical group of patients with small bowel anastomosis, the level of zinc upon admission to the hospital was significantly increased. In the second stage, we conducted a study on the detection of an increase in serum iron content, endogenous intoxication and a decrease in transferrin iron saturation depending on the clinical course of the disease in patients with acute intestinal obstruction and peritonitis and the degree of contamination of the small intestine. The results shown in study indicate that in the studied patients, depending on the severity of the disease there is a progressive decrease in the content of iron in whole blood, along with an increase in its serum level against the background of a significant decrease in iron saturation and increase in objective indicators of endogenous intoxication.&#x0D; Conclusions. On the basis of the results of the research, we can conclude that the increase of serum iron content with simultaneous decrease of transferrin iron saturation in the studied patients on the background of intensification of endotoxicosis depending on the severity of the condition, considering it as a factor of increasing the aggressiveness of bacterial resistance and flora correlates with the severity of the clinical course, according to which appropriate adequate additional corrective therapy is performed in complex surgery. treatment of patients with a small bowel anastomosis.

IRON DEFICIENCY IN HEART FAILURE

Background: Data on the burden of Iron deficiency (ID) in Heart failure (HF) patients in India are sparse and there is very little information available about the prevalence of iron deficiency in heart failure with mid-range (HFmrEF) and preserved ejection fraction (HFpEF) in comparison to heart failure with reduced ejection-fraction (HFrEF).&#x0D; Aims and Objective: This study was carried out with aim to evaluate iron profile in HF patients and to know the prevalence of ID in HFpEF, HFmrEF and HFrEF in our region.&#x0D; Materials and Methods: Patients with clinically diagnosed HF were enrolled in the study. This was a single tertiary care centre, prospective, observational study carried out from December 2017 to November 2018. Patients were classified into HFrEF, HFmrEF and HFpEF on echocardiography. Serum ferritin (micrograms per liter), serum iron (micrograms per liter), total iron binding capacity (micrograms per liter), transferrin (milligrams per deciliter), and transferrin saturation were measured to assess iron status. Absolute ID was defined as serum ferritin &lt; 100 mg/L and functional ID was defined as normal serum ferritin (100–300 mg/L) with low TSAT (&lt;20%).&#x0D; Results: A total of 120 patients of HF (66.7% males and 33.3% females) were studied. Out of 120 patients, 78 (65%) patients of HF had ID. Absolute ID was in 38.3% and functional ID was seen in 26.7% patients. 62.5% of males had ID, whereas, 70% of females had ID in HF. Patients with ID had higher NYHA Class, 35.9% compared to 23.8% patients without ID. ID was high in all subsets of HF. ID was found in 61.11% in HFrEF, 67.44% in HFmrEF and 69.57% in HFpEF. P-0.71. 14.1% patients had ID, but no anemia (p- 0.02). In anemic patients, ID was more (85.2%) than non anemic patients (69%).&#x0D; Conclusion: In our study, prevalence of ID was higher in patients of HF than that reported from western literature. HFpEF had higher prevalence of ID followed by HFmrEF and HFrEF, respectively. Literature is scanty about HFmrEF, our study has given an insight of ID in this subset of HF. ID can occur even without anemia and females are more prone to have ID in HF. Our study highlights the importance of diagnosis and treatment of ID in all subsets of HF, in order to improve quality of life, morbidity and mortality in patients of HF.&#x0D; Keywords: Iron deficiency, Heart Failure, Anemia, HFrEF, HFmrEF, HFpEF

Regulation of the Transferrin Receptor Recycling in Hepatitis C Virus-Replicating Cells.

After binding of its ligand transferrin, the transferrin receptor (TfR) is internalized via early endosomes. Ligand and receptor can be recycled. α-Taxilin was identified as an essential factor for TfR recycling. Apart from its role for iron uptake, TfR is a coreceptor for hepatitis C virus (HCV) infection. In HCV-replicating cells, the amount of a-taxilin is decreased. This study aims to investigate the effect of decreased α-taxilin levels in HCV-replicating cells on recycling of TfR, its amount on the cell surface, on iron uptake, and the impact of a disturbed TfR recycling on HCV superinfection exclusion. TfR amount and localization were determined by CLSM and surface biotinylation. α-taxilin expression was modulated by CRISPR-Cas9 knockout, siRNA, and stable or transient overexpression. For analysis of HCV superinfection fluorophor-tagged reporter viruses were used. The amount of α-taxilin is decreased in HCV-infected cells. In accordance to this, the protein amount of TfR is significant lower in HCV-positve cells as compared to the control, while TfR expression is not affected. Due to the impaired recycling, internalized TfR is degraded by the endosomal/lysosomal system. The significant lower number of TfR molecules on the cell surface is reflected by reduced transferrin binding/internalization and strong reduction of intracellular iron level. Overexpression of α-taxilin in HCV-replicating cells rescues TfR recycling, augments TfR on the cell surface, and restores transferrin binding. The block of superinfection in HCV-replicating cells could be overcome by overexpression of α-taxilin. Taken together, the diminished level of α-taxilin in HCV-replicating cells prevents recycling of TfR leading to decreased transferrin binding and iron uptake. Disappearance of TfR from the cell surface could be a factor contributing to the exclusion of superinfection by HCV.

Study of Glycation of Transferrin and its Effect on Biomarkers of Iron Status in Uncontrolled Diabetes Mellitus Patients

Introduction: Diabetes Mellitus (DM) is a metabolic condition linked by the inability to produce enough insulin and/or to respond to insulin. This can lead to a number of acute and chronic health problems. In erythrocytes, transferrin is the main source of iron. Alterations in transferrin glycation affect transferrin saturation because the affinity of transferrin for Fe3+ is extremely high but it decreases progressively with increasing glycation. Aim: To investigate the influence of uncontrolled diabetes on transferrin glycation and iron metabolism. Materials and Methods: A total of 136 samples from 3 groups of HbA1c levels (&lt;6.0% non-diabetic, 6.4-8% diabetic, &gt;8.0%-uncontrolled DM) were studied for the correlation pattern of iron with other variables. Chi square test and student’s t-test were performed to reveal the association between serum free iron levels and other variables with DM. Results: Serum iron has shown to be depleted significantly (p=0.02) along with percentage saturation (p=0.0006) with increase in diabetic severity. No significant differences were observed in serum ferritin in controlled DM and uncontrolled samples. Total Iron Binding Capacity (TIBC) was found to be significantly increased in uncontrolled DM samples (p=0.01). Abnormal transferrin was observed uncontrolled diabetes with subsequent depletion in transferrin, which in turn results in low serum iron, lower percentage saturation and high TIBC. Conclusion: Uncontrolled diabetes affects the glycation of transferrin also thus perturbating iron metabolism. The present study emphasises the need to monitor transferrin glycation status and iron deficiency anaemia in subjects with uncontrolled diabetes.

Green colored plasma discovered in a male blood donor: A cause for concern?

The normal color of plasma is yellow, which is owing to the presence of factors such as bilirubin, hemoglobin, carotenoids, and iron transferrin. We recently came across an interesting case of greenish colored plasma in our blood bank. An extensive literature survey revealed that our conspicuous finding was not an isolated one and that similar such rare incidents have been reported in the past, on a sporadic basis. Several diverse reasons have been attributed to the peculiar greenish color like the presence of high ceruloplasmin levels, Pseudomonas aeruginosa infection and so on, but they were ruled out in our case. We thus, report our finding of greenish colored plasma in an otherwise healthy donor because of the rarity of its occurrence and also, to allay any sense of fear or alarm that an encounter may raise in the blood bank staff.