Changes in Hepcidin Levels in an Animal Model of Anemia of Chronic Inflammation: Mechanistic Insights Related to Iron Supplementation and Hepcidin Regulation

We examined changes in hepcidin (closely associated with anemia of chronic inflammation (ACI)) and upstream regulatory pathways after intravenous (IV) iron supplementation in an ACI animal model. ACI was induced in male Sprague-Dawley rats by intraperitoneally administering complete Freund’s adjuvant (CFA). Two weeks after starting CFA treatment, ACI rats received IV iron (CFA-iron) or vehicle (CFA-saline). Three days after IV iron treatment, iron profiles, hepcidin levels, and expression of proteins involved in the signaling pathways upstream of hepcidin transcription in the liver were measured. In CFA-treated rats, anemia with a concomitant increase in the levels of serum inflammatory cytokines and reactive oxygen species occurred. In CFA-iron rats, hemoglobin (Hb) concentration was still lower than that in control rats. In CFA-saline rats, hepatic hepcidin and ferritin levels increased compared with those in control rats and were further increased in CFA-iron rats. In CFA-saline rats, NADPH oxidase- (NOX-) 2, NOX-4, and superoxide dismutase levels in the liver were upregulated compared with those in control rats and their levels were further increased in CFA-iron rats. In CFA-saline rats, activities of the IL-6/STAT and BMP/SMAD pathways were enhanced in the liver compared with those in control rats and their levels were further increased in CFA-iron rats, whereas IL-6 expression remained unaffected after IV iron administration. In HepG2 cells, iron caused phosphorylation of STAT-3 and SMAD1/5 and knockdown of STAT-3 and SMAD1/5 using siRNAs reduced iron-induced hepcidin upregulation to levels similar to those in corresponding control cells. Renal erythropoietin expression and serum erythroferrone concentration were lower in CFA-iron rats than those in control rats. In ACI rats, IV iron supplementation did not recover Hb within three days despite an increase in hepatic ferritin levels, which might be attributable to an additional increase in hepcidin levels that was already upregulated under ACI conditions. Both STAT-3 phosphorylation and SMAD1/5 phosphorylation were associated with hepcidin upregulation after IV iron treatment, and this seems to be linked to iron-induced oxidative stress.

EVALUATION OF THE THERAPEUTIC EFFECT OF THE COMBINED USE OF CRYOPRESERVED PLACENTA EXTRACT AND DICLOFENAC SODIUM IN EXPERIMENTAL RHEUMATOID ARTHRITIS BY HEMATOLOGICAL PARAMETERS

Relevance. Cryopreserved placenta extract (CPE) increase the resistance of the mucous membrane of the gastrointestinal tract to the damaging effects of nonsteroidal anti-inflammatory drugs. Preventive administration of CPE can reduce the ulcerogenic effect of meloxicam, ibuprofen, diclofenac sodium (DS) and others. There is evidence of CPE's own anti-inflammatory activity, which can be successfully combined with the pharmacological properties of nonsteroidal anti-inflammatory drugs, while improving their safety profile. Objective: to characterize the therapeutic activity of the combined use of CPE and DS according to hematological parameters in the model of experimental rheumatoid arthritis (RA). Materials and methods. Studies were performed on 28 nonlinear laboratory rats. The rats were divided into 4 groups: I (n = 7) – intact rats; II (n = 7) – rats with experimental RA; ІІІ (n = 7) – rats with experimental RA, treated with DN; IV (n = 7) – rats with experimental RA, treated with DN and CPE. Adjuvant arthritis was modeled by subplantar administration of complete Freund's adjuvant. Treatment was performed from 14 to 28 days. CPE was administered on days 14, 17, 20, 23 and 26, and DS – daily. Blood tests were performed on day 28 of the experiment. Results. The combined use of CPE and DS is accompanied by a more pronounced leveling of inflammatory signs by hematological parameters – erythrocyte clotting rate decreased by 72.2% (p<0.001), and the number of leukocytes decreased by 54.81% (p<0.001) relative to rats with adjuvant arthritis without treatment. There was a leveling of signs of anemia of chronic inflammation – the level of hemoglobin and erythrocytes increased (p<0,001) by 17.6% and 36.8%, respectively, relative to rats with adjuvant arthritis without treatment. Conclusions. The combined use of CPE and DS is superior in therapeutic activity to monotherapy with this nonsteroidal anti-inflammatory drug of experimental rheumatoid arthritis.

The Association Between Anemia of Chronic Inflammation and Alzheimer’s Disease and Related Dementias

Background: Dementia is a spectrum of neurological diseases characterized by memory impairment and cognitive decline with the pathogenesis and effective management remaining elusive. Several studies have identified a correlation between anemia and Alzheimer’s disease and related dementias (ADRD); however, anemia subtypes and association with ADRD have yet to be studied conclusively. Objective: To study an association between ADRD and anemia of chronic inflammation. Methods: We conducted a retrospective case-control study of the patients, diagnosed with ADRD at Brookdale Hospital. Pair-wise comparisons between means of controls and cases in terms of iron studies and laboratory results were performed using a Mann–Whitney U test. Pair-wise comparisons between anemia subgroups (moderate and severe) were performed using a Two Sample proportion Z-Test, where for each couple of normally distributed population. Results: There was a total of 4,517 (1,274 ADRD group; 3,243 Control group) patients. There was significant difference in hemoglobin 10.15 versus 11.04 [p-value <0.001]. Iron studies showed a significant difference in ferritin 395±488.18 versus 263±1023.4 [p < 0.001], total iron binding capacity 225±84.08 versus 266±82.30 [p < 0.001] and serum iron level 64±39.34 versus 53±41.83 [p < 0.001]. Folic acid and vitamin B12 levels were normal in both groups. Severe and moderate anemia in the ADRD group were respectively 6.2% [95% CI: 4.2–8.4] and 13% [95% CI: 9.8–16.2] higher. Overall, incidence of moderate-to-severe anemia was found to be 19% higher in ADRD group [95% CI: 15.8–22.1]. Conclusion: We demonstrated an association between ADRD and anemia of chronic inflammation independent of age, renal function, and HgbA1C levels.

Hemoglobin Levels and Serum C-Reactive Protein in Patients With Moderate to Severe Hidradenitis Suppurativa

Introduction: Anemia of chronic inflammation is associated with many inflammatory diseases. Little is known about anemia in hidradenitis suppurativa (HS). This study aimed to review the levels of hemoglobin (Hb) and investigate its relationship with serum C-reactive protein (CRP) and disease severity in HS patients. Methods: This was a retrospective chart review of all HS patients from 2015 to 2017 with Hb and CRP blood work. Patient demographics, disease severity, and laboratory results were extracted. Data were analyzed descriptively. A linear regression model was used for the association between Hb and CRP. Two-tailed t-tests and one-way ANOVA were used to compare differences between sexes and disease severities. Results: Of the 25 patients included, 14 (56%) were female. The median age and disease duration of all patients were 41 years (range, 19-56 years) and 10 years (range, 1-40 years), respectively. The overall median CRP level was 11.5 mg/dL (range, 1-86.7 mg/dL). The median Hb levels for women and men were and 123.5 g/L (range, 90-142 g/L) and 152.0 g/L (range, 109-166 g/L), respectively. Anemia was found in 42.9% (6/14) of women and 27.3% (3/11) of men. There was an inverse relationship between Hb and CRP levels in both sexes (men: r = ‒0.88; P = .0006; women r = ‒0.65; P = .012). Conclusions: Anemia was prevalent in the HS population, and Hb levels inversely correlated with CRP. Physicians should be aware that anemia is common in inflammatory states, and that CRP could be a biomarker in patients with HS.

Aptamer Oligonucleotides as Potential Therapeutics in Hematologic Diseases

: Aptamers are single-stranded DNA or RNA oligonucleotides generated by a novel in vitro selection technique termed Systematic evolution of ligands by exponential enrichment (SELEX). During the past two decades, various aptamer drugs have been developed and many of them have entered into clinical trials. : In the present review, we focus on aptamers as potential therapeutics for hematological diseases, including anemia of chronic inflammation (ACI) and anemia of chronic disease (ACD), hemophilia, thrombotic thrombocytopenic purpura (TTP) or VWD type-2B, and sickle cell disease (SCD), in particular, those that have entered into clinical trials

A young lady with inflammation of unknown origin

Takayasu’s arteritis (TAK) is a systemic vasculitis mainly affecting the aorta and its first branches. The initial presentation can be very non-specific while its sequelae can be debilitating and fatal. Apart from clinical and biochemical tests, imaging studies remain pivotal for the diagnosis of this rare disease. Delay in treatment may result in vascular stenosis, leading to morbidity and mortality. We report a case of a young woman who presented with anemia with no obvious causes. Subsequently she developed ischemic symptoms and the diagnosis of TAK was established with magnetic resonance angiography (MRA). Our case illustrates the importance of recognition of the possibility of TAK in young women who presented with non-specific systemic upset and anemia of chronic inflammation. A high index of suspicion is needed and imaging studies should be considered early. The treatment of TAK will also be briefly reviewed.

The Levels of Hepcidin and Erythropoietin in Pregnant Women with Anemia of Various Geneses

AIM: The purpose of the present research was to study the content of erythropoietin and hepcidin in serum in pregnant women with iron deficiency anaemia and anaemia of chronic inflammation. METHODS: The authors examined 98 pregnant women who were observed in LLP (Regional obstetric-gynaecological centre) in Karaganda. The including criteria for pregnant women in the study was the informed consent of the woman to participate in the study. Exclusion criteria were oncological diseases, HIV-infection, tuberculosis, severe somatic pathology, mental illness, drug addiction. The design of the study was by the legislation of the Republic of Kazakhstan, international ethical norms and normative documents of research organisations, approved by the ethics committee of the Karaganda State Medical University. RESULTS: As a result of the study, it was determined that the content of erythropoietin and hepcidin in pregnant women with anemias of different genesis varies ambiguously. In the main group of pregnant women with IDA, the erythropoietin content rises, and the hepcidin level decreases. In pregnant women with ACI, on the contrary, the level of hepcidin increases, and in one subgroup it is significant. However, in pregnant women and with IDA and anemia of chronic inflammation, there is a subgroup of women in whom erythropoietin is either comparable with hepcidin, or their changes are of opposite nature. CONCLUSION: The authors concluded that the obtained data indicate ambiguous changes in the level of erythropoietin and hepcidin in pregnant women with anaemias of various origins. In all likelihood, there are still unaccounted factors affecting the content of these protein-regulators of iron metabolism, which require further definition and interpretation in anaemia of pregnant women.