Iron Transferrin Saturation Research Articles

Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis

To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Pharmacokinetics, pharmacodynamics, and tolerability of an aqueous formulation of rusfertide (PTG-300), a hepcidin mimetic, in healthy volunteers: A double-blind first-in-human study.

Rusfertide is a potent peptide mimetic of hepcidin being investigated for the treatment of polycythemia vera. This randomized, placebo-controlled, double-blind study evaluated the safety, pharmacokinetics, and pharmacodynamics of single and repeated subcutaneous doses of an aqueous formulation of rusfertide in healthy adult males. Subjects received single doses of 1, 3, 10, 20, 40, or 80 mg rusfertide or placebo. A separate cohort of subjects received two doses of 40 mg rusfertide or placebo 1 week apart. Blood samples for pharmacokinetics and pharmacodynamics were collected, and adverse events, clinical laboratory tests, 12-lead electrocardiograms, and vital signs were monitored. Rusfertide was well tolerated. There were no serious or severe treatment-emergent adverse events, and no patterns of clinically important adverse events, or laboratory, vital sign, or electrocardiogram abnormalities. Mean maximum rusfertide plasma concentration (Cmax) and area under the concentration-time curve increased with dose, but less than dose proportionally. Median time to Cmax was 2-4.5 h for 40 and 80 mg rusfertide and 8-24 h for lower doses. Apparent clearance and half-life increased with dose. Single doses of rusfertide 1-80 mg were associated with dose-dependent decreases in serum iron and transferrin-iron saturation. Rusfertide was well tolerated and showed dose-dependent pharmacokinetics and pharmacodynamics.

Iron deficiency in patients with cancer: a prospective cross-sectional study

BackgroundDespite the deleterious consequences of iron deficiency (ID) in patients with cancer, underdiagnosis is frequent. The CARENFER study aimed to assess the prevalence of ID using both serum ferritin concentration...

Association of Iron Profile with Type 2 Diabetes Mellitus:Review

This minireview assesses the correlation between iron profile levels and type 2 diabetes mellitus. Iron, ferritin, transferrin saturation, and total iron-binding capacity (TIBC) are examples of iron profiles. Every study included in this review shows that type 2 diabetics' blood serum has less iron overall and less iron-binding capacity. Conversely, the same studies' findings showed that individuals with type 2 diabetes had higher levels of ferritin in their blood serum. In terms of transferrin (iron) saturation, a number of studies show that it is rising, while a smaller number shows that it is falling in the blood serum of those who have type 2 diabetes. These investigations led to the conclusion that there is substantial evidence linking the iron profile to type 2 diabetic mellitus (T2DM). Reduced transferrin levels are connected to a lower risk of Type 2 Diabetes Mellitus, but higher serum iron, ferritin, and transferrin saturation are associated with an increased risk. There is also genetic evidence that links elevated systemic iron status to a higher risk of type 2 diabetes.

Analysis of iron status after initiation of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis.

Iron deficiency is highly prevalent in people with cystic fibrosis (PwCF). While elexacaftor/tezacaftor/ivacaftor (ETI) has shown remarkable improvements in respiratory symptoms in PwCF, the effect of ETI on iron status remains unknown. This study aims to identify the effect of ETI on iron status in PwCF. A single-center retrospective cohort study of 127 adult PwCF was conducted to assess the impact of ETI on iron, ferritin, transferrin levels, and percent saturation of transferrin (PSAT). Data were collected from the electronic medical record from January 2017 to September 2022, encompassing 2 years before and after ETI initiation. The primary outcome was serum iron parameters: iron, ferritin, transferrin, and PSAT levels following ETI treatment. Secondary outcomes analyzed iron supplementation. Univariate and multivariate mixed-effects models were used for the analysis of ETI. After adjusting for covariates, following ETI initiation, the mean iron level increased by 20.24 μg/dL (p < .001), ferritin levels were 31.4% (p < .001) higher, PSAT showed a 5.09 percentage point increase (p < .001), and transferrin levels increased by 2.71 mg/dL (p = .439). Patients with and without iron supplementation experienced a significant increase in iron after ETI (p < .001). ETI is associated with a significant increase in iron, ferritin, and PSAT levels. Patients with and without iron supplementation demonstrated a significant increase in iron. This study shows the benefits of ETI on iron status in PwCF. However, further translational studies are required to understand the impact of ETI on iron absorption and metabolism in PwCF.

Rusfertide for the treatment of iron overload in HFE-related haemochromatosis: an open-label, multicentre, proof-of-concept phase 2 trial

Hereditary haemochromatosis protein (HFE)-related haemochromatosis, an inherited iron overload disorder caused by insufficient hepcidin production, results in excessive iron absorption and tissue and organ injury, and is treated with first-line therapeutic phlebotomy. We aimed to investigate the efficacy and safety of rusfertide, a peptidic mimetic of hepcidin, in patients with HFE-related haemochromatosis. This open-label, multicentre, proof-of-concept phase 2 trial was done across nine academic and community centres in the USA and Canada. Adults (aged ≥18 years) with HFE-related haemochromatosis on a stable therapeutic phlebotomy regimen (maintenance phase) for at least 6 months before screening and who had a phlebotomy frequency of at least 0·25 per month (eg, at least three phlebotomies in 12 months or at least four phlebotomies in 15 months) and less than one phlebotomy per month, with serum ferritin of less than 300 ng/mL and haemoglobin of more than 11·5 g/dL, were eligible. Patients initiated 24 weeks of subcutaneous rusfertide treatment within 7 days of a scheduled phlebotomy at 10 mg once weekly. Rusfertide doses and dosing schedules could be adjusted to maintain serum transferrin iron saturation (TSAT) at less than 40%. During rusfertide treatment, investigators were to consider the need for phlebotomy when the serum ferritin and TSAT values exceeded the patient's individual pre-phlebotomy serum ferritin and TSAT values. No primary endpoint or testing hierarchy was prespecified. Prespecified efficacy endpoints included the change in the frequency of phlebotomies; the proportion of patients achieving phlebotomy independence; change in serum iron, TSAT, serum transferrin, serum ferritin, and liver iron concentration (LIC) as measured by MRI; and treatment-emergent adverse events (TEAEs). The key efficacy analyses for phlebotomy rate and LIC were conducted by use of paired t tests in the intention-to-treat population, defined as all patients who received any study drug and who had pretreatment and at least one post-dose measurement. We included all participants who received at least one dose of rusfertide in the safety analyses. This trial is closed and completed and is registered with ClinicalTrials.gov, NCT04202965. Between March 11, 2020, and April 23, 2021, 28 patients were screened and 16 (ten [63%] men and six [38%] women) were enrolled. 16 were included in analyses of phlebotomy endpoints and 14 for the LIC endpoint. 12 (75%) patients completed 24 weeks of treatment. The mean number of phlebotomies was significantly reduced during the 24-week rusfertide treatment (0·06 phlebotomies [95% CI -0·07 to 0·20]) compared with 24 weeks pre-study (2·31 phlebotomies [95% CI 1·77 to 2·85]; p<0·0001). 15 (94%) of 16 patients were phlebotomy-free during the treatment period. Mean LIC in the 14 patients in the intention-to-treat population was 1·4 mg iron per g dry liver weight (95% CI 1·0 to 1·8) at screening and 1·1 mg iron per g dry liver weight (95% CI 0·9 to 1·3) at the end of treatment (p=0·068). Mean TSAT was 45·3% (95% CI 33·2 to 57·3) at screening, 36·7% (24·2 to 49·2) after the pretreatment phlebotomy, 21·8% (15·8 to 27·9) 24 h after the first dose of rusfertide, 40·4% (27·1 to 53·8) at the end of treatment, and 32·6% (25·0 to 40·1) over the treatment duration. Mean serum iron was 24·6 μmol/L (95% CI 18·6 to 30·6), 20·1 μmol/L (14·8 to 25·3), 11·9 μmol/L (9·2 to 14·7), 22·5 μmol/L (15·9 to 29·1), and 19·0 μmol/L (15·3 to 22·6) at these same timepoints, respectively. Mean serum ferritin was 83·3 μg/L (52·2 to 114.4), 65·5 μg/L (32·1 to 98·9), 62·8 μg/L (33·8 to 91·9), 150·0 μg/L (86·6 to 213.3), and 94·3 μg/L (54·9 to 133.6) at these same timepoints, respectively. There were only minor changes in serum transferrin concentration. 12 (75%) patients had at least one TEAE, the most common of which was injection site pain (five [31%] patients). All TEAEs were mild or moderate in severity, except for a serious adverse event of pancreatic adenocarcinoma, which was considered severe and unrelated to treatment and was pre-existing and diagnosed 21 days after starting rusfertide treatment. Rusfertide prevents iron re-accumulation in the absence of phlebotomies and could be a viable therapeutic option for selected patients with haemochromatosis. Protagonist Therapeutics.

Pathogenetic Effects of Bacteria of the Genus &lt;i&gt;Desulfovibrio&lt;/i&gt;. Experimental Study. Part One: Iron Metabolism

The aim of the work was to study specific systemic effect of sulfate-reducing bacteria of the genus Desulfovibrio on organism systems through creating an experimental model of intragastric bacterial invasion against the background of dysbiotic conditions of rodent gastrointestinal tract. Materials and methods. The experimental study was conducted on Wistar rats. Intestinal dysbiosis was modeled with the help of antibiotics, amoxicillin and metronidazole. Typical strain Desulfovibrio desulfuricans subsp. desulfuricans VKM B-1799T was used as an infectious agent. Results and discussion. As a result of the experiment performed, during the period of acute infection (on day 15 of the experiment), a direct correlation between the concentration of the injected D. desulfuricans VKM B-1799T bacteria suspension and the serum iron level was observed: the higher the infectious agent dose, the lower the serum iron concentration. During the phase of remote effects (day 38 of the experiment), the inverse correlation between the concentrations of D. desulfuricans VKM B-1799T in the intestines of rodents was revealed: when the concentration of the infecting agent increased from 103 CFU/g and higher, the iron level decreased from 43.5 μmol/l to 38.5 μmol/l. When comparing the level of transferrin and unsaturated iron binding capacity (UIBC), an increase in those parameters was observed in all groups of rats both during the period of acute infection and the period of long-term effects, and the percentage of transferrin iron saturation decreased, indicating the occurrence of iron deficiency against the background of exposure to the infectious agent. Intestinal dysbiosis promotes colonization by opportunistic flora, including Desulfovibrio sp. Changes in the iron metabolism markers in experimental animals against the background of D. desulfuricans VKM B-1799T infestation above 103 CFU/g and the ability of this microorganism to bind iron into an unavailable form suggest that the bacteria Desulfovibrio sp. are one of the key etiological factors of iron deficiency anemia.

Characteristics of clinical and laboratory parameters in patients with chronic heart failure of elderly and senile age with iron deficiency

Relevance. The frequency of chronic heart failure (CHF) increases with age. A common pathology in patients with CHF is iron deficiency (ID). Age may contribute to development of ID in patients with CHF. The purpose of the study: To study the features of clinical and laboratory parameters in elderly and senile patients with CHF, depending on the presence of ID. Materials and methods: 2 groups of patients with CHF 2-4 functional class were examined: group 1-60-74 years (146 patients, mean age 68.1±3.1), group 2-75 years and older (127 patients, mean age 78.3±2.2). All patients underwent a clinical examination, a 6-minute walk test, a general blood test, the determination of the level of iron, ferritin, transferrin in blood serum, iron saturation of transferrin, soluble transferrin receptors, hepcidin, interleukin-6, C-reactive protein, the presence and severity of asthenia, anxiety, depression. Results. It has been established that patients in the senile group have a significantly higher functional life expectancy and more pronounced clinical and laboratory manifestations of CHF (the worst 6-minute walk test, more pronounced manifestations of asthenia and depression, a higher concentration of NT-proBNP, hepcidin), compared with elderly patients. The presence of ID in both age groups increases the manifestations of physical asthenia and anxiety. Conclusions: 1) the severity of clinical manifestations of CHF in senile patients is significantly higher than in elderly patients; 2) in senile patients, the levels of hepcidin and latent ID are significantly higher than those in elderly patients; 3) latent ID in both age groups increases the manifestations of physical asthenia and anxiety; 4) it is advisable to conduct early diagnosis of latent ID in all patients with CHF of elderly and, especially, senile age for the timely detection of this condition and the appointment of therapy for correcting ID.

ЭФФЕКТИВНОСТЬ ВНУТРИВЕННОГО ВВЕДЕНИЯ ЖЕЛЕЗА (III) ГИДРОКСИД САХАРОЗНОГО КОМПЛЕКСА У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ С СОХРАНЕННОЙ ФРАКЦИЕЙ ВЫБРОСА И ДЕФИЦИТОМ ЖЕЛЕЗА

Abstract. Introduction. Iron deficiency is diagnosed in 59% of patients with chronic heart failure with preserved ejection fraction. The efficacy of iron therapy in these patients has not been studied. Aim. The purpose of the study is to study the effectiveness of intravenous administration of iron (III) hydroxide sucrose complex in patients with chronic heart failure with preserved ejection fraction and iron deficiency. Material and methods. A study was conducted on 55 patients with ischemic heart disease and/or hypertension complicated by chronic heart failure with preserved ejection fraction with iron deficiency (14 men and 41 women), mean age 71.88±6.90 years. Patients of the main group (30 people) in addition to traditional therapy received iron (III) hydroxide-sucrose complex, patients of the control group (25 people) received only traditional therapy. In all patients, functional activity, the severity of clinical manifestations, asthenia, anxiety, depression, quality of life were assessed, echocardioscopy, complete blood count, and iron metabolism were determined. All examinations in the main and control groups were performed before the start of the study, after 2 weeks of therapy, 2 and 6 months after the end of treatment. Statistical analysis of the results at different observation times was performed using Stata/MP version 14.0 and MedCalc Statistical Software version 18.2.1. Results and discussion. The inclusion of iron (III) hydroxide sucrose complex in the complex therapy of iron-deficient patients with chronic heart failure with preserved ejection fraction increases the level of iron, ferritin, hemoglobin and transferrin iron saturation and reduces clinical manifestations of heart failure, severity of asthenia, anxiety, depression and increases physical performance and quality of life. The positive effect of the iron preparation appears by the end of the course of treatment, reaches a maximum after 2 months and lasts for 6 months. Conclusion. To increase the effectiveness of the treatment of patients with chronic heart failure with preserved ejection fraction and iron deficiency, it is recommended to conduct complex therapy, including, in addition to traditional treatment the administration of iron (III) sucrose hydroxide complex.

Iron overload disorders.

Iron overload disorders represent a variety of conditions that lead to increased total body iron stores and resultant end‐organ damage. An elevated ferritin and transferrin‐iron saturation can be commonly encountered in the evaluation of elevated liver enzymes. Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D, mutations most encountered in hereditary hemochromatosis, should be pursued in evaluation of hyperferritinemia. Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy (especially if liver disease is a cause of iron overload) should be used as appropriate. A secondary cause for iron overload should be considered if HFE genetic testing is negative for the C282Y homozygous or C282Y/H63D compound heterozygous mutations. Differential diagnosis of secondary iron overload includes hematologic disorders, iatrogenic causes, or chronic liver diseases. More common hematologic disorders include thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency. If iron overload has been excluded, evaluation for causes of hyperferritinemia should be pursued. Causes of hyperferritinemia include chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions, such as adult‐onset Still's disease or hemophagocytic lymphohistiocytosis. In this review, we describe the diagnostic testing of patients with suspected hereditary hemochromatosis, the evaluation of patients with elevated serum ferritin levels, and signs of secondary overload and treatment options for those with secondary iron overload.

Evaluating risk factors for catheter-related infections in hemodialysis patients

Introduction: Catheter-related infection in the patients with end-stage renal disease (ESRD) is one of the leading causes of death. Identifying risk factors for infection, including patients’ iron profile, plays an important role in preventing this complication. Objectives: In this study, we aimed to determine the risk factors of catheter-related infections among the ESRD patients in Qazvin, Iran. Patients and Methods: In this observational study, 41 patients with hemodialysis venous catheter-related infection (case group) and 42 patients without catheter-related infection ( control group) in Qazvin educational and medical centers were studied. The definition of functional iron deficiency anemia included ferritin &lt;500 ng/mL and serum iron/total iron-binding capacity (TIBC) &lt;30%. The laboratory evaluation method was based on enzyme-linked immunosorbent assay method. Definition of catheter-related infection in this study consisted of two positive results of the three cultures from blue and red catheter lines and blood at the same time with the same microorganism. Results: In studying iron parameters, a significant difference between serum iron levels and transferrin saturation in the two groups was detected (P values of 0.0016 and 0.003, respectively). Both parameters were higher in the control group. The most common microorganism causing the infection was Staphylococcus aureus (43.9%) and most of the catheters used were of temporary internal jugular vein types. The most important risk factors in the incidence of catheter infection were diabetes mellitus (OR = 5.059) and high serum iron levels (OR = 1.053). Decreased transferrin saturation levels reduced the risk of infection (OR = 0.825). Conclusion: There was a relationship between iron profile and diabetes mellitus and the increased risk of catheter-related infections. To prevent infection, patients with ESRD undergoing hemodialysis with venous catheters, blood sugar and serum iron levels need to be monitored carefully and iron overdose should be prevented in these patients.

The effect of beet juice-based foods on the performance of athletes in cyclic sports

BACKGROUND: Modern data from the scientific literature indicate that nitrate, when added to food, can serve as a precursor of nitric oxide (NO). According to research results, the concentrations of nitrates and nitrites in plasma increase when subjects are taking dietary supplements containing nitrates. Such an increase not only contributes to training performance by activating the nitrate pathway of energy supply to muscle activity but also generally improves physical performance.&#x0D; AIMS: To evaluate the effect of consumption of beet juice, as a source of nitrates, on the performance of biathletes-sprinters.&#x0D; MATERIALS AND METHODS: Forty male biathletes aged from 18 to 22 years took part in the study. The study took place in a training camp in the summer of 2017. The athletes were divided into an experimental group and a control group. The experimental group was given a preparation containing beet juice of a special variety twice daily after each training session, and the athletes of the control group did not consume anything after training sessions. Before the experiment and after 20 days of intervention, load testing before work refusal was carried out, as well as biochemical and general blood analysis.&#x0D; RESULTS: In the athletes of the experimental group, who were consuming beet juice, there was a decrease in oxygen uptake per kilogram of body weight and an increase in heart rate at the moment of anaerobic threshold, as well as an increase in load time, which indicates an increase in endurance during anaerobic exercise. This parameter is one of the limiting factors of performance in cyclic sports. In addition, increases in blood iron content, transferrin saturation, hemoglobin concentration, and average erythrocyte volume were observed in participants who consumed the beet juice preparation.&#x0D; CONCLUSIONS: The observed changes in indicators of the oxygen-transport system of the blood may be one of the mechanisms through which exogenous nitrates realize their positive effect on performance in the anaerobic phase.

CHANGES IN PROTEIN AND LIPID PEROXIDATION IN ORGANS OF HEPATOPANCREATOBILIARY SYSTEM, ENZYMATIC ANTIOXIDANTS IN RATS UNDER THE CONDITIONS OF DIETS WITH EXCESSIVE CARBOHYDRATES OR FATS

Among the mechanisms of pathological processes development, in particular obesity, an important role belongs to the increase in the intensity of oxygen-dependent processes. It is known that the products of protein and lipid peroxidation can change the structure of the cell membrane, lead to denaturation of proteins and damage to amino acids. Accumulation of protein and lipid peroxidation products can inhibit oxidative phosphorylation and glycolysis, can cause tissue edema and worsen the course of inflammatory processes. Such changes may occur against the background of inertia or suppression of antioxidant reserves. The in-depth study of the obesity development against the background of high-carbohydrate or high-fat diets attracts attention.&#x0D; The aim of the research was to study the peculiarities of indices of the oxygen-dependent processes and anti-radical protection of the body against the background of a high-calorie diet during the experiment. The study was performed using mature male rats on a diet with excessive amount of carbohydrates (experimental group 1) and fats (experimental group 2) and on a standard diet of vivarium (control group).&#x0D; As a result of the study in the blood serum of experimental rats there was observed an increased content of products of the oxidative modification of proteins in the blood serum at 64.35% – 3.3-fold (p˂0.05), in liver tissues – 2.6-4.5-fold (p˂0.01) and pancreas at 67.86% – 5.6-fold (p˂0.05) regarding the control group data. Changes in lipoperoxidation indices were unidirectional. In particular, in the blood serum of animals on high-carbohydrate and high-fat diets there was an increase in the content of diene conjugates (DC) and products that react to thiobarbituric acid (TBA-AP) at 72.37% – 2.2-fold (p˂0.001), in the tissues of liver and pancreas – an increase in the level of TBA-AP at 44.07% – 6.0-fold (p˂0.01), respectively regarding the control. There were no significant differences found between the studied indices of protein and lipid peroxidation in animals of the experimental groups 1 and 2. The resulting changes may indicate a number of abnormalities (structural rearrangement of hepatocyte membranes, impaired cellular metabolism and energy metabolism, increased unsaturated fatty acids), which in turn can lead to the development of diabetes mellitus and obesity.&#x0D; Activation of protein and lipid peroxidation occurred under the conditions of increased catalase activity at 2.5-3.4-fold (p˂0.05), ceruloplasmin content at 54,61-88,65% (р˂0,05), iron transferrin saturation at 43,58-51,28% (р˂0,01) against the background of reduced superoxide dismutase and glutathione reductase activity (at 26,84-83,34% р˂0,01) regarding the values in intact animals. The determined changes of antioxidant reserve did not depend on the diet type. Such changes may indicate a corresponding strain on the functional abilities of the antioxidant system during the increase in the intensity of oxidative stress under the conditions of obesity.&#x0D; The resulting disorders reflect the development of oxidative stress and are the risk factors for structural adjustments and functional changes in the hepatopancreatobiliary system organs. Activation of the processes of free radical oxidation of proteins and lipids against the background of inhibition of antioxidant enzymes can play a significant role in the development of obesity complications, especially such as hypertension, atherosclerosis, heart failure, type 2 diabetes mellitus.

Large-scale retrospective analyses of the effect of iron deficiency anemia on hemoglobin A1c concentrations

IntroductionHbA1c is a reliable biomarker for diagnosing and prognosis of diabetes, but many clinical scenarios and interfering factors can affect the test results. Any conditions that affect red cell turnover, such as iron-deficiency anemia (IDA), can lead to spurious HbA1c results. Reports on how IDA affects HbA1c concentrations are contradictory, and to understand better the association between HbA1c concentrations and IDA, we conducted a large-scale retrospective study. MethodsTest results for HbA1c concentrations were retrieved from the years 2015–2019. We evaluated over 12,000 patients with IDA and 21,000 patients without IDA. Patients were classified as having IDA if samples with below the age-based ranges for serum iron, ferritin, or transferrin iron saturation and above age-based ranges for transferrin iron-binding capacity or transferrin concentrations. Kruskal–Wallis statistical analyses method was used to test whether the two samples follow the same distribution and significance. ResultsThe median HbA1c concentration was 5.7% among IDA classified patients and 5.4% among normal samples (P < 0.001) for females. For males, the median HbA1c concentration was 6.0% among IDA classified patients and 5.6% among normal samples (P < 0.001). ConclusionPatients classified as IDA can have increased HbA1c concentrations than patients without IDA. Clinicians should consider IDA status before making therapeutic decisions based on HbA1c concentrations.

Crosstalk between Acidosis and Iron Metabolism: Data from In Vivo Studies.

Iron absorption requires an acidic environment that is generated by the activity of the proton pump gastric H(+)/K(+)ATPase (ATP4), expressed in gastric parietal cells. However, hepcidin, the iron regulatory peptide that inhibits iron absorption, unexpectedly upregulates ATP4 and increases gastric acidity. Thus, a concept of link between acidosis and alterations in iron metabolism, needs to be explored. We investigated this aspect in-vivo using experimental models of NH4Cl-induced acidosis and of an iron-rich diet. Under acidosis, gastric ATP4 was augmented. Serum hepcidin was induced and its mRNA level was increased in the liver but not in the stomach, a tissue where hepcidin is also expressed. mRNA and protein levels of intestinal DMT1(Divalent Metal Transporter 1) and ferroportin were downregulated. Serum iron level and transferrin saturation remained unchanged, but serum ferritin was significantly increased. Under iron-rich diet, the protein expression of ATP4A was increased and serum, hepatic and gastric hepcidin were all induced. Taken together, these results provide evidence of in-vivo relationship between iron metabolism and acidosis. For clinical importance, we speculate that metabolic acidosis may contribute in part to the pathologic elevation of serum hepcidin levels seen in patients with chronic kidney disease. The regulation of ATP4 by iron metabolism may also be of interest for patients with hemochromatosis.

Iron supplementation ameliorates aloin-induced iron deficiency anemia in rats

Aloin, an anthraquinone glycoside, is one of other C-glycosides found in the leaf exudate of Aloe plant. Aloin possesses several biologic activities, including antitumor activity in vitro and in vivo. However, aloin treatment has shown iron deficiency anemia and erythropoiesis in vivo. The present study was undertaken to verify if iron supplementation could alleviate these perturbations, compared to doxorubicin, an anthracycline analog. Oral iron supplementation (20.56 mg elemental Fe/kg bw) to aloin-treated rats normalized red blood corpuscles count, hemoglobin concentration, and serum levels of total iron binding capacity and saturated transferrin, as well as hepatic iron content, hepcidin level, and mRNA expression of ferritin heavy chain (Ferr-H) and transferrin receptor-1 (TfR-1) genes. Although, serum hyperferremia, and leukocytosis were maintained, yet the spleen iron overload was substantially modulated. However, combined aloin and iron treatment increased iron storage levels in the heart and bone marrow, compared to aloin treatment per se. On other hand, oral iron supplementation to rats treated with doxorubicin (15 mg/kg bw) lessened the increase in the spleen iron content concomitantly with hepatic hepcidin level, rebound hepatic iron content to normal level, and by contrast augmented serum levels of iron and transferrin saturation. Also, activated Ferr-H mRNA expression and repressed TfR-1 mRNA expression were recorded, compared to doxorubicin treatment per se. Histopathological examination of the major body iron stores in rats supplemented with iron along with aloin or doxorubicin showed an increase in extramedullary hematopoiesis. In conclusion, iron supplementation restores the disturbances in iron homeostasis and erythropoiesis induced by aloin treatment.

REGULATION OF ANTIOXIDANT ENZYMES IN PATIENTS AFTER PERIODONTAL TREATMENT WITH NATURAL AGENTS

The aim: The study of the possibilities of oxidase-antioxidant system indicators regulation at patients with periodontitis under the influence of complex treatment. Materials and methods: 36 healthy and 125 patients with chronic and exacerbated periodontitis of primary (22 and 21), I (21) and II (20) degrees were examined.Indicators of lipid peroxidation and antioxidant protection (levels of diene conjugates and malonic dialdehyde, catalase activity and transferrin iron saturation, ceruloplasmin activity) in the blood serum were studied before, 6 and 12 months after the appointed treatment. Initial periodontal therapy and a paste developed by us (spirulina microalgae powders and silica enterosorbent taken in equal amounts and 0.05% chlorhexidine bigluconate) for applications and instillations were exogenously used in the complex treatment. Spirulina tablets were prescribed per os as well. Results: All patients exhibit elevated levels of diene conjugates and malonic dialdehyde, decreased catalase activity and transferrin iron saturation as well as an increased ceruloplasmin activity, especially pronounced at stages I and II (p1≤0.01-0.001). Treatment contributed to long-term and reliable (p2&lt;0.05 - 0.001) regulation of the studied parameters: reduction of diene conjugates and malonic dialdehyde, ceruloplasmin activity and increased catalase activity and transferrin iron saturation. All indicators differed slightly from the norm during the year (p1&gt;0.05), and complete normalization of most of them lasted six months. At the same time clinical stabilization of periodontitis was reached. Conclusions: Indicators of the oxidase-antioxidant system in patients with periodontitis are significantly altered and indicate their participation in the pathogenesis of the disease. Complex treatment was able to almost completely normalize them within six months, but a year later the difference between the obtained indicators with data in healthy people was insignificant (except for ceruloplasmin). Clinical stabilization was achieved in all patients.

Scientific reviews. Principles of diagnosis and treatment of iron deficiency anemia in children

Annotation.In Europe, the overall prevalence of iron deficiency anemia is 2-4%, with two peaks: young children (2.3-15%) and adolescents (3.5-13% – in boys, 11-33% – in girls). Iron deficiency occurs earlier than anemia, which is characterized by a decrease in the size and iron saturation of erythrocytes, and they become microcytic and hypochromic. Therefore, anemia can be prevented by early diagnosis and treatment of latent iron deficiency. The aim of the work was to analyze and systematize the main problematic issues of diagnosis and treatment of iron deficiency anemia in children. To conduct the study, we analyzed databases PubMed, Cochrane Library, Google Scholar, etc., referring to the vast majority of publications from the last five years (2016-2021), in addition to three articles published in 2012 and 2014. The main criteria for selecting sources were: the availability of the latest methods for the diagnosis of anemia, modern methods of treatment of iron deficiency anemia in children. Analysis of the identified literature sources showed that iron deficiency in the laboratory and clinically can manifest itself at different stages. Negative iron balance, which persists after a decrease in iron stores, is manifested by a decrease in hemoglobin and the development of anemia. A decrease in the number of erythrocytes or the level of hemoglobin (Hb) by 5 percentile below the normal value of hemoglobin, determined for a given age in healthy people, is called anemia. Routine screening for iron deficiency should be performed in children aged 6 to 24 months. Screening consists of identifying risk factors and laboratory testing if available. Determination of serum ferritin during the first screening is the main diagnostic tool in children with risk factors for iron deficiency and signs of anemia. Ferritin levels should always be carefully evaluated, as ferritin is nonspecifically elevated in a variety of inflammatory conditions. Other screening tests, such as reticulocyte levels, iron transferrin saturation, and serum iron-binding capacity, are performed to confirm the diagnosis. The choice and route of administration of iron requires consideration of the cause that led to its deficiency, the severity of symptoms and condition of the patient, the probable and desired rate of hematological response, risks and complications of treatment, availability of resources and preferences of the patient. Oral iron remains a priority for the treatment of children with iron deficiency anemia, but it is necessary to consider situations where first-line therapy will be administered by intravenous means. Thus, based on the analysis of the literature, we can conclude that iron deficiency anemia remains an urgent medical and social problem today. Children with iron deficiency anemia develop cognitive impairment that does not fully recover even after treatment. Therefore, further research aimed at improving methods of prevention, early diagnosis and treatment of iron deficiency anemia in different age groups of children should be promising.

Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial.

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40–60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40–60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50–58% of the 40–60 mg/Kg/day DFO-treated patients.

The Changes of Prooxidant-Antioxidant and Energy Homeostasis in Rates with Impaired Glucose Tolerance

Topicality.Violation of glucose utilization leads to disruption of all types of metabolic processes. Particularly dangerous in the prognostic aspect is the combination of carbohydrate metabolism disorders and other endocrine pathologies, in particular hypothyroid dysfunction.&#x0D; The objective of the study was to examine prooxidant-antioxidant changes ofblood serum, teeth pulp and oral mucosa in rats with impaired glucose tolerance on the background of iodine deficiency.&#x0D; Materials and Methods. The studies were carried on 60 female rats, which were divided into two research groups - rats with impaired glucose tolerance and insulin resistance on the background of iodine deficiency. Lipid peroxidation processes were evaluated due to the content of diene conjugates and active products that react with thiobarbituric acid in blood serum, teeth pulp and oral mucosa. Antioxidant defence of blood serum was characterized by catalase, ceruloplasmin, superoxide dismutase, glutathione peroxidase, glutathione reductase activity and iron transferrin saturation. Energy metabolism was examined by the activity of succinate dehydrogenase, malate dehydrogenase and lactate dehydrogenase in blood serum.&#x0D; Results.Impaired glucose tolerance was foundto lead to the activation of lipoperoxidation, mainly due to the accumulation of final products of lipid peroxidation in all studied tissues against the background of redistribution of the activity of antiradical enzymes. Under these experimental conditions, different changes in the activity of energy synthesis enzymes were observed. The development of combined endocrine pathology has led to more pronounced changes in the prooxidant-antioxidant system and significant suppression of serum dehydrogenase activity.&#x0D; Conclusions.The development of insulin resistance on the background of iodine deficiency causes the activation of oxygen-dependent processes in periodontal tissues against the background of reduced antiradical defence and disruption of energy synthesis system.