scholarly journals Management of Anaemia of Chronic Disease: Beyond Iron-Only Supplementation

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 237
Author(s):  
Evasio Pasini ◽  
Giovanni Corsetti ◽  
Claudia Romano ◽  
Roberto Aquilani ◽  
Tiziano Scarabelli ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Essential Amino Acids ◽  
Iron Therapy ◽  
Human Metabolism ◽  
Heme Synthesis ◽  
Anaemia Of Chronic Disease ◽  
Amino Levulinic Acid ◽  
Precursor Molecules ◽  
Worse Prognosis

Chronic diseases are characterised by altered autophagy and protein metabolism disarrangement, resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia is linked to a worse prognosis independent of the target organ affected by the disease. Currently, the cornerstone of the therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of haematopoiesis. However, treatment strategies should incorporate the promotion of the synthesis of heme, the principal constituent of haemoglobin (Hb) and of many other fundamental enzymes for human metabolism. Heme synthesis is controlled by a complex biochemical pathway. The limiting step of heme synthesis is D-amino-levulinic acid (D-ALA), whose availability and synthesis require glycine and succinil-coenzyme A (CoA) as precursor substrates. Consequently, the treatment of anaemia should not be based only on the sufficiency of iron but, also, on the availability of all precursor molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate a standard iron infusion and a supply of essential amino acids and vitamins involved in heme synthesis. We reported preliminary data in a select population of aged anaemic patients affected by congestive heart failure (CHF) and catabolic disarrangement, who, in addition to the standard iron therapy, were treated by reinforced therapeutic schedules also providing essential animo acids (AAs) and vitamins involved in the maintenance of heme. Notably, such individualised therapy resulted in a significantly faster increase in the blood concentration of haemoglobin after 30 days of treatment when compared to the nonsupplemented standard iron therapy.

scholarly journals Management of Anemia of Chronic Disease: Beyond Iron-Only Supplementation.

2020 ◽  
Author(s):  
Evasio Pasini ◽  
Giovanni Corsetti ◽  
Claudia Romano ◽  
Roberto Aquilani ◽  
Tiziano Scarabelli ◽  
...  
Keyword(s):  
Iron Supplementation ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Essential Amino Acids ◽  
Iron Therapy ◽  
Iron Availability ◽  
Anemia Of Chronic Disease ◽  
Heme Synthesis ◽  
Biochemical Constituent ◽  
Worse Prognosis

Chronic diseases are characterised by cell’s autophagy and proteins disarrangement resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia couses worse prognosis independentely of the principal disease. Currently, the cornerstone of therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of hematopoiesis. However, treatment strategies should incorporate the addition of heme, the principal biochemical constituent of haemoglobin. Heme synthesis follows a complex biochemical pathway. The limiting step of heme synthesis is D-ALA availability which, for its synthesis, requires Glycine and Succinil-CoA. Consequently, treatment of anaemia should not be based only on iron availability, but also on the availability of the molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate the standard iron infusion and the supply of essential amino acids and vitamins involved in the heme synthesis. We report preliminary data in selected elderly anaemic patients with congestive heart failure (CHF) and catabolic disarrangement, who, in addition to standard iron therapy, received personalized therapy with essential-AAs and vitamins involved in the maintenance of heme. Notably, such individualized therapy resulted in a significant increase in the serum concentration of haemoglobin after 30 days of treatment compared to standard iron therapy.

scholarly journals Potential Use of Interleukin-10 Blockade as a Therapeutic Strategy in Human Cutaneous Leishmaniasis

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Lucio Roberto Castellano ◽  
Laurent Argiro ◽  
Helia Dessein ◽  
Alain Dessein ◽  
Marcos Vinícius da Silva ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Therapeutic Strategy ◽  
Interleukin 10 ◽  
Leishmania Braziliensis ◽  
Soluble Antigen ◽  
Innovative Strategies ◽  
Host Protection ◽  
Human Cutaneous Leishmaniasis ◽  
Potential Use ◽  
Worse Prognosis

Interleukin-10 overproduction has been associated with worse prognosis in human cutaneous leishmaniasis, while IFN-γ-dependent responses are associated with parasite killing and host protection. Innovative strategies are needed to overcome therapeutic failure observed in endemic areas. The use of monoclonal antibody-based immunotherapy targeting IL-10 cytokine was evaluated here. Partial IL-10 blockade inLeishmania braziliensiswhole soluble antigen-stimulated cells from endemic area CL patients with active or healed lesions and asymptomatic controls was evaluated. Overall decrease in IL-10, IL-4, and TNF-αproduction was observed in all groups of subjects. Only patients with active lesions still produced some levels of TNF-αafter anti-IL-10 stimulation in association withLeishmaniaantigens. Moreover, this strategy showed limited modulatory effects on IFN-γ-dependent chemokine CXCL10 production. Results suggest the potential immunotherapeutic use of partial IL-10 blockade in localized cutaneous leishmaniasis.

scholarly journals IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3144-3152 ◽  
Author(s):  
Carolina Schinke ◽  
Orsolya Giricz ◽  
Weijuan Li ◽  
Aditi Shastri ◽  
Shanisha Gordon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Strategy ◽  
In Vivo Models ◽  
Cxcr2 Expression ◽  
Key Points ◽  
Pathway Inhibition ◽  
Worse Prognosis

Key Points IL8-CXCR2 is overexpressed in purified stem cells from AML and MDS, and CXCR2 expression is associated with worse prognosis. Inhibition of CXCR2 by genetic and pharmacologic means leads to decreased viability in AML/MDS stem cells and in vitro and in vivo models.

Glycine Supplementation – A Novel Therapeutic Strategy for Congenital Sideroblastic Anemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2087-2087
Author(s):  
Jason N Berman ◽  
Pedro Fernandez-Murray ◽  
Gheyath Nasrallah ◽  
Noelia Dufay ◽  
Conrad V Fernandez ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Aminolevulinic Acid ◽  
Protein Product ◽  
Microcytic Anemia ◽  
Model Systems ◽  
Transcription Activator ◽  
Zebrafish Model ◽  
Heme Synthesis ◽  
Beta Galactosidase

Abstract Abstract 2087 Congenital sideroblastic anemias (CSA) are inherited diseases, characterized by ineffective haematopoiesis, typically severe microcytic anemia and bone marrow sideroblasts representing excess iron deposition in the mitochondria of the erythroid precursors. More than 40% of CSA cases are attributed to mutations in the X-linked gene ALAS2. ALAS2 encodes the mitochondrial enzyme aminolevulinic acid synthase-2, which utilizes glycine to form 5-aminolevulinic acid (5-ALA), a crucial precursor in heme synthesis. Another gene, SLC25A38, has recently been implicated in the abnormal heme development noted in CSA. The function of the SLC25A38 protein product is uncertain, although it is thought to be an erythroid specific mitochondrial carrier family protein, transporting glycine across mitochondrial membranes. We employed yeast and zebrafish model systems in parallel to evaluate the absence of SLC25A38 or ALAS2 on heme synthesis in vivo and identify potential therapeutic strategies. HEM1 (ALAS2 homologue) mutant yeast were completely unable to make heme, whereas heme synthesis was significantly reduced in YDL119c (SLC25A38 homologue) mutant yeast. To monitor heme synthesis, we utilized a beta-galactosidase reporter linked to Pcyc1, which is only active following binding of the yeast Hap1 transcription activator in the presence of heme. Both HEM1 and YDL119c mutant yeast showed no beta-galactosidase activity, however activity in the YDL119c mutant was returned to 30% with the addition of 5-ALA and to 40% following treatment with glycine. Microarray studies of untreated and glycine treated YDL119c mutant yeast revealed increased expression of genes required to synthesize vitamin B6, a cofactor for the Hem1 enzyme in yeast and humans. Morpholino (MO)-mediated knockdown of the zebrafish homologues of SLC25A38 (slc25a38a and slc25a38b) or alas2 correlated with decreased hemoglobin levels by o-dianisidine staining and increased embryonic malformation and mortality. 5-ALA treatment either by addition to the egg water or by injection into the yolk failed to restore hemoglobinization in alas2 morphant embryos. By contrast, the addition of glycine to the egg water resulted in upregulation of hemoglobin to near normal levels in the majority of slc25a38a/b double morphant embryos. Our study demonstrates conserved heme synthesis pathways through evolution across species and further supports the contention that SLC25A38 functions as a glycine transporter. Most significantly, glycine supplementation emerged as an effective therapeutic strategy to restore heme synthesis in CSA caused by SLC25A38 deficiency, providing the rationale to support use of glycine in a clinical trial that is under development for these patients. Disclosures: McMaster: DeNovaMed: Equity Ownership.

scholarly journals Neuroinflammation as a Therapeutic Target in Retinitis Pigmentosa and Quercetin as Its Potential Modulator

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1935
Author(s):  
Joseph Thomas Ortega ◽  
Beata Jastrzebska
Keyword(s):  
Inflammatory Response ◽  
Retinitis Pigmentosa ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Photoreceptor Cells ◽  
Rod Photoreceptors ◽  
Inflammatory Reactions ◽  
Environmental Light ◽  
The Stability ◽  
Visual Receptor

The retina is a multilayer neuronal tissue located in the back of the eye that transduces the environmental light into a neural impulse. Many eye diseases caused by endogenous or exogenous harm lead to retina degeneration with neuroinflammation being a major hallmark of these pathologies. One of the most prevalent retinopathies is retinitis pigmentosa (RP), a clinically and genetically heterogeneous hereditary disorder that causes a decline in vision and eventually blindness. Most RP cases are related to mutations in the rod visual receptor, rhodopsin. The mutant protein triggers inflammatory reactions resulting in the activation of microglia to clear degenerating photoreceptor cells. However, sustained insult caused by the abnormal genetic background exacerbates the inflammatory response and increases oxidative stress in the retina, leading to a decline in rod photoreceptors followed by cone photoreceptors. Thus, inhibition of inflammation in RP has received attention and has been explored as a potential therapeutic strategy. However, pharmacological modulation of the retinal inflammatory response in combination with rhodopsin small molecule chaperones would likely be a more advantageous therapeutic approach to combat RP. Flavonoids, which exhibit antioxidant and anti-inflammatory properties, and modulate the stability and folding of rod opsin, could be a valid option in developing treatment strategies against RP.

scholarly journals Krukenberg Tumor: A Review of Prognostic Factors and Management

2020 ◽  
pp. 1-4
Author(s):  
Adrian Murillo Zolezzi
Keyword(s):  
Abdominal Mass ◽  
Treatment Strategies ◽  
Signet Ring Cell ◽  
Current Evidence ◽  
Primary Ovarian Cancer ◽  
Signet Ring ◽  
Common Clinical Presentation ◽  
Ring Cell ◽  
Krukenberg Tumors ◽  
Worse Prognosis

Aim: This review aims to summarize current evidence on Krukenberg Tumors (KT), addressing the main prognostic determinants and its’ management. Background: Krukenberg Tumors are rare metastatic tumors of the ovary. They were initially described by Friederich Ernst Krukenberg in 1896. They arise from extra-ovarian primary signet-ring cell carcinomas, being the gastrointestinal tract the most common site of origin. The most common clinical presentation of KT is an abdominal mass or discomfort in a premenopausal 40 to the 50-year-old woman. The prognosis is extremely poor compared to primary ovarian cancer. Results: Overall survival may vary significantly according to the choice and timing of treatment. The effective treatment strategies for KT are still controversial. However, therapeutic options include surgical resection as the mainstay of treatment when possible and the application of different Chemotherapy (CT) regimens. Conclusions: Several factors negatively affect prognosis: an incomplete metastasectomy, extensive disease at diagnosis and the origin of the tumor are the main factors that most authors agree incur in a worse prognosis. KT’s optimal therapeutic strategies are still a matter of debate, raising the need for more studies to achieve consensus.

scholarly journals Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy

2021 ◽  
Vol 22 (17) ◽  
pp. 9257
Author(s):  
Chih-Hung Tsai ◽  
Yuan-Ho Lin ◽  
Yung-Sheng Li ◽  
Trung-Loc Ho ◽  
Le Huynh Hoai Thuong ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Peripheral Neuropathy ◽  
Recent Progress ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Common Side Effect ◽  
Integrated Medicine ◽  
Effective Prevention ◽  
Effective Strategies ◽  
Prevention And Treatment

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

scholarly journals Tumor-Associated Microglia and Macrophages in the Glioblastoma Microenvironment and their Implications for Therapy

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4255
Author(s):  
Rikke Sick Andersen ◽  
Atul Anand ◽  
Dylan Scott Lykke Harwood ◽  
Bjarne Winther Kristensen
Keyword(s):  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Therapeutic Strategies ◽  
The Poor ◽  
Temozolomide Chemotherapy

Glioblastoma is the most frequent and malignant primary brain tumor. Standard of care includes surgery followed by radiation and temozolomide chemotherapy. Despite treatment, patients have a poor prognosis with a median survival of less than 15 months. The poor prognosis is associated with an increased abundance of tumor-associated microglia and macrophages (TAMs), which are known to play a role in creating a pro-tumorigenic environment and aiding tumor progression. Most treatment strategies are directed against glioblastoma cells; however, accumulating evidence suggests targeting of TAMs as a promising therapeutic strategy. While TAMs are typically dichotomously classified as M1 and M2 phenotypes, recent studies utilizing single cell technologies have identified expression pattern differences, which is beginning to give a deeper understanding of the heterogeneous subpopulations of TAMs in glioblastomas. In this review, we evaluate the role of TAMs in the glioblastoma microenvironment and discuss how their interactions with cancer cells have an extensive impact on glioblastoma progression and treatment resistance. Finally, we summarize the effects and challenges of therapeutic strategies, which specifically aim to target TAMs.

Interventionelle Behandlung der Mitralklappe – was gibt es Neues 2019?

2019 ◽  
Vol 144 (22) ◽  
pp. 1553-1560
Author(s):  
Maria Isabel Körber ◽  
Roman Pfister ◽  
Stephan Baldus
Keyword(s):  
Heart Failure ◽  
Mitral Valve ◽  
Treatment Strategies ◽  
Interventional Treatment ◽  
Prognostic Impact ◽  
Interventionelle Behandlung ◽  
High Operative Risk ◽  
Secondary Mr ◽  
Very High ◽  
Worse Prognosis

AbstractMitral regurgitation (MR) is one of the most common valvular defects in the eldery. In patients suffering from heart failure, secondary MR is common and associated with worse prognosis. Due to the usually very high operative risk these patients are immensely under-treated. This leads to an increased need for interventional treatment strategies. Until now there were no randomized data regarding the prognostic impact of interventional treatment of secondary MR. This article is supposed to sum up evidence derived from recent studies regarding this issue. Finally we will provide an outlook on catheter-based mitral valve prothesis.

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