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Anemia of Chronic Diseases: Wider Diagnostics-Better Treatment?

Anemia of chronic diseases is a condition that accompanies a specific underlying disease, in which there is a decrease in hemoglobin, hematocrit and erythrocyte counts due to a complex process, usually initiated by cellular immunity mechanisms and pro-inflammatory cytokines and hepcidin. This is the second most common type of anemia after iron deficiency anemia in the world. Its severity generally correlates with the severity of the underlying disease. This disease most often coexists with chronic inflammation, autoimmune diseases, cancer, and kidney failure. Before starting treatment, one sho

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… It binds to ferroportin, which limits the release of iron from enterocytes, monocytes, macrophages and hepatocytes into the blood. … Thanks to DMT1 protein (divalent metal transporter 1), iron passes into the enterocyte and then it is released into the blood by ferroportin. Hepcidin produced by the liver limits the release of iron from enterocytes into the blood by binding to ferroportin. …

Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement.

Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two establis

Disorders of the Gastrointestinal System

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… For example, Clostridium difficile toxin A activates a neural pathway that triggers mast cell degranulation and neutrophil influx into the tissue. 8 , 9 Blockade of this neural pathway is sufficient to abolish the profound inflammatory response induced by toxin A and many of the effects of toxin A on enterocyte … Products of activated neutrophils (TNF-α and interferon-γ) increase tight junction permeability by direct effects on the enterocytes. Prostaglandins released by activated neutrophils stimulate epithelial secretion, thus contributing to diarrhea. …

Pharmacological Strategies for Mitigating Cytarabine-Induced Multi-Organ Toxicity: A Scoping Review on Mechanisms, Efficacy and Clinical Implications.

BACKGROUND: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. OBJECTIVES: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-org

Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity.

PurposeHaematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever.MethodsThis prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia 500/mL or discharge.ResultsWe included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of cit

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… Citrulline, an amino acid produced by enterocytes, is a biomarker of intestinal integrity [ 16 ]. … Demacker PN, Beijers AM, van Daal H, Donnelly JP, Blijlevens NM, van den Ouweland JM (2009) Plasma citrulline measurement using UPLC tandem mass-spectrometry to determine small intestinal enterocyte pathology. J Chromatogr B Analyt Technol Biomed Life Sci 877(4):387–392 19. …

Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre.

The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019-January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 fema

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… A significant progress in etiology/etiopathogenesis of (especially primary) BAM has been made: fibroblast growth factor 19 (FGF-19), an endocrine substance which is being released from enterocytes (upon a high intracellular bile acid level in enterocytes) into the portal circulation, activates FGF receptor …

Feline infectious peritonitis.

The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.

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… It is now known that cats are infected with the primarily avirulent FCoV that replicates in enterocytes. … They are shaped so that they can bind specifically to topical enterocytes. Replication of nonmutated FCoV is thus primarily restricted to enterocytes. The mutated FIP-causing FCoV has a broader cell spectrum, including macrophages. …

The Interplay between Immune System and Microbiota in Osteoporosis.

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becom

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… It is expressed on both immune and not-immune cells, such as enterocytes. A recent study has identified TLR5 as a new mediator in the process of inflammation-induced bone loss and osteoclastogenesis, through the activation of RANKL pathway [ 40 ]. … Lactobacillus rhamnosus and Lactobacillus plantarum also increase serum vitamin D, through a higher expression of VDR in both mouse and human enterocytes [ 73 ]. VDR knockout animals exhibit a decreased presence of lactobacilli compared to clostridium and bacteroides [ 74 ]. …

New Biomarkers of Ferric Management in Multiple Myeloma and Kidney Disease-Associated Anemia.

Multiple myeloma (MM) is a malignancy of clonal plasma cells accounting for approximately 10% of haematological malignancies. MM mainly affects older patients, more often males and is more frequently seen in African Americans. The most frequent manifestations of MM are anaemia, osteolytic bone lesions, kidney failure and hypercalcemia. The anaemia develops secondary to suppression of erythropoiesis by cytokine networks, similarly to the mechanism of anaemia of chronic disease. The concomitant presence of kidney failure, especially chronic kidney disease (CKD) and MM per se, leading to anaemia

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… Iron circulation in the human body is associated with four cell types: enterocytes involved in iron absorption; erythroblasts—the precursors of red blood cells (RBCs); splenic macrophages degrading aged RBCs and releasing iron back to the bone marrow via transferrin; and hepatocytes playing a role in … Non-haem iron (after reduction to Fe 2+ by membrane-bound enzymes), originating from dietary intake (mostly Fe 3+ ), enters the enterocyte of the proximal intestine via the divalent metal transporter (DMT1), and exits the cell on the basolateral side through ferroportin (FPN), which is potentiated by …

Treatment with anti-IL-6 receptor antibody prevented increase in serum hepcidin levels and improved anemia in mice inoculated with IL-6-producing lung carcinoma cells.

BackgroundHepcidin, a key regulator of iron metabolism, is produced mainly by interleukin-6 (IL-6) during inflammation. A mechanism linking cancer-related anemia and IL-6 through hepcidin production is suggested. To clarify the hypothesis that overproduction of IL-6 elevates hepcidin levels and contributes to the development of cancer-related anemia, we evaluated anti-IL-6 receptor antibody treatment of cancer-related anemia in an IL-6-producing human lung cancer xenograft model.MethodsNude mice were subcutaneously inoculated with cells of the IL-6-producing human lung cancer cell line LC-06-J

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… Hepcidin is a 25-amino acid peptide hormone produced mainly in the liver that regulates intestinal iron absorption by causing degradation of the enterocyte iron transporter ferroportin, iron recycling by macrophages, and iron release from hepatic stores [ 4 , 6 ]. … We hypothesized that excess hepcidin may interfere with erythropoiesis by inhibiting iron release from hepatic storage as ferritin levels were high in this model and by inhibiting iron uptake from diet and export from enterocytes to blood as serum iron level was decreased, consequently possibly causing …

The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde?

The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the

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… The SGLT1 glucose transporter is essential in glucose metabolism regulation and is expressed by absorptive enterocytes. Its expression is regulated by EEC-secreted peptide hormones such as GLP-1,2. [ 38 ]. … On the surface of absorptive enterocytes, CaSR can regulate intestinal calcium and other divalent absorption and anion secretion. …

Возможная роль метаформы и фибробластного роста Factor-21 В Multical Sclerosis Neuropathology: Birds of a Feather Flock Common.

Множественный склероз (MS) — прогрессивное демиелинизирующее заболевание CNS, характеризующееся воспалением, образованием CNS-клеров и повреждением нейронной миелинской оболочки (graphical abstract). Фактор роста фибробласта 21 (FGF21) занимается различными метаболическими расстройствами и нейродегенеративными заболеваниями. FFF21 и его корецептор β-Kloth имеют существенно важное значение для процесса ремиелиции MS. Метформин, инсулин-сенсибилизирующее лекарство, которое является первой линией лечения для типа 2 Мэлитус диабета (T2DM) может оказывать потенциальное нейрозащитное воздействие, ре

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… Metformin is an orally administered medication, absorbed in the small intestine through the highly expressed plasma membrane monoamine transporter (PMAT) in enterocytes (Al‐Kuraishy, Al‐Gareeb, Alblihed, Cruz‐Martins, et al.  2021 ; Al‐Kuraishy, Al‐Gareeb, Waheed, and Al‐Maiahy  2018 ; Al‐Kuraishy et … AMPK enhances anaerobic glucose metabolism and insulin sensitivity in enterocytes (Abdul‐Hadi, Naji, Shams, et al.  2020 ) (Figure  3 ). …

Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra.

High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinr

The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

Anemia in Chronic obstructive pulmonary disease: Prevalence, pathogenesis, and potential impact.

Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable lifestyle-related disease with high global prevalence. COPD is associated with significant morbidity and mortality worldwide. Comorbidities are important events in the natural history of the disease and have a negative effect on the morbidity and mortality of COPD patients. Cardiac diseases, lung cancer, osteoporosis, and depression are common comorbidities reported for COPD. Recently, anemia has been recognized as a frequent comorbidity in COPD patients. The prevalence of anemia in patients with COPD varies fro

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… Iron is released from the duodenal enterocyte, macrophage, and hepatocyte via a special membrane iron exporter called ferroportin. … Hepcidin modulates the ferroportin level posttranslationally by binding to the ferroportin and induces its internalization and degradation in lysosomes as shown in Figure 1 .[ 35 ] This Hepcidin–ferroportin interaction is responsible for trapping iron in the hepatocytes, macrophages, and absorptive enterocytes …

Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.

BACKGROUND: Peripheral neuropathy and gastrointestinal dysfunction are frequent, debilitating side effects of the neurotoxic myeloma drug bortezomib that reduce quality of life and adherence to optimal therapy. Therapeutic strategies to manage these complications are limited. Here, we have developed a mouse model of bortezomib side effects to investigate the role of the gut microbiota in their development. METHODS: C57BL/6 specific pathogen-free (SPF), germ-free (GF) and ex-GF mice (colonised with healthy gut microbiota via faecal microbiota transplantation [FMT]) were treated with bortezomib

Hypophosphatemic rickets: diagnosis and treatment.

Hypophosphatemicrickets (HR) represents a heterogeneous group of disorders characterized by renal phosphate wasting, impaired bone mineralization, and skeletal deformities. This narrative review provides an overview of phosphate homeostasis and the molecular mechanisms underlying HR, focusing on the role of Fibroblast Growth Factor 23 (FGF23) in regulating renal phosphate use and vitamin D metabolism. The clinical, biochemical, and genetic features of both FGF23-dependent and -independent forms of HR are discussed, including X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic

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… Approximately 30% of dietary phosphate is absorbed through the sodium-dependent phosphate cotransporter NPT2b ( SLC34A2 ) located on the apical membrane of enterocytes in the jejunum and ileum ( 3 ) . … Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell. 2008;19(5):1912–1921. doi: 10.1091/mbc.e07-09-0973.. 28. King AJ, Siegel M, He Y, Nie B, Wang J, Koo-McCoy S, et al. …

Gut-Bone Axis: A Non-Negligible Contributor to Periodontitis.

Periodontitis is a polymicrobial infectious disease characterized by alveolar bone loss. Systemic diseases or local infections, such as diabetes, postmenopausal osteoporosis, obesity, and inflammatory bowel disease, promote the development and progression of periodontitis. Accumulating evidences have revealed the pivotal effects of gut microbiota on bone health via gut-alveolar-bone axis. Gut pathogens or metabolites may translocate to distant alveolar bone via circulation and regulate bone homeostasis. In addition, gut pathogens can induce aberrant gut immune responses and subsequent homing o

Biology and Diseases of Dogs

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… With Warthin–Starry silver staining, C. jejuni may be seen between enterocytes but only rarely inside them. Pathogenesis. Clinical disease may be produced by several different mechanisms after the Campylobacter has populated the intestinal tract ( Van Kruiningen, 1995 ). … After colonization of the enterocyte surface, C. jejuni can produce an enterotoxin that causes a secretory diarrhea. …

Длительное использование цинка для дисгейзии, вызывающее нехватку меди.

Цинк является микроэлементом, необходимым для восприятия вкуса и может быть прописан для дисгейзии у больных раком, проходящих лечение. Однако чрезмерное потребление цинка может привести к дефициту меди, который, скорее всего, недооценивается и может представлять собой усталость, тошноту, анемию и миэлопатию. КИСЛОТА: Пациент в 70-летнем возрасте с несколькими миэломой и гастропарезом, принимающий добавки цинка для лечения дисгейсии в прошлом. 2 Годы, порожденные общей усталостью, головокружением, тошнотой, нейтрализмом, анемией, походом, а также ухудшением онемения и покалыванием в нижних кон

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… Excess zinc increases copper-binding protein metallothionein in the enterocytes, causing copper to be bound and eliminated with sloughing of intestinal cells; this ultimately leads to copper depletion (Halfdanarson et al. 2008 ). …