scholarly journals The Role of Eryptosis in the Pathogenesis of Renal Anemia: Insights From Basic Research and Mathematical Modeling

2020 ◽  
Vol 8 ◽  
Author(s):  
Gabriela Ferreira Dias ◽  
Nadja Grobe ◽  
Sabrina Rogg ◽  
David J. Jörg ◽  
Roberto Pecoits-Filho ◽  
...  
Keyword(s):  
Life Span ◽  
Kidney Failure ◽  
Basic Research ◽  
Cytosolic Calcium ◽  
Renal Anemia ◽  
Phagocytic Cells ◽  
Healthy Humans ◽  
Outer Leaflet ◽  
Rbc Membrane ◽  
Cation Permeability

Red blood cells (RBC) are the most abundant cells in the blood. Despite powerful defense systems against chemical and mechanical stressors, their life span is limited to about 120 days in healthy humans and further shortened in patients with kidney failure. Changes in the cell membrane potential and cation permeability trigger a cascade of events that lead to exposure of phosphatidylserine on the outer leaflet of the RBC membrane. The translocation of phosphatidylserine is an important step in a process that eventually results in eryptosis, the programmed death of an RBC. The regulation of eryptosis is complex and involves several cellular pathways, such as the regulation of non-selective cation channels. Increased cytosolic calcium concentration results in scramblase and floppase activation, exposing phosphatidylserine on the cell surface, leading to early clearance of RBCs from the circulation by phagocytic cells. While eryptosis is physiologically meaningful to recycle iron and other RBC constituents in healthy subjects, it is augmented under pathological conditions, such as kidney failure. In chronic kidney disease (CKD) patients, the number of eryptotic RBC is significantly increased, resulting in a shortened RBC life span that further compounds renal anemia. In CKD patients, uremic toxins, oxidative stress, hypoxemia, and inflammation contribute to the increased eryptosis rate. Eryptosis may have an impact on renal anemia, and depending on the degree of shortened RBC life span, the administration of erythropoiesis-stimulating agents is often insufficient to attain desired hemoglobin target levels. The goal of this review is to indicate the importance of eryptosis as a process closely related to life span reduction, aggravating renal anemia.

scholarly journals Initial assessment of the beneficial effect of partial splenectomy in hereditary spherocytosis

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2014-2020 ◽  
Author(s):  
G Tchernia ◽  
F Gauthier ◽  
F Mielot ◽  
JP Dommergues ◽  
J Yvart ◽  
...  
Keyword(s):  
Life Span ◽  
Hereditary Spherocytosis ◽  
Reticulocyte Count ◽  
Clinical Manifestations ◽  
Partial Splenectomy ◽  
Initial Assessment ◽  
Phagocytic Function ◽  
Normal Range ◽  
Rbc Membrane ◽  
Technetium Uptake

Clinical manifestations of hereditary spherocytosis (HS), the most common red blood cell (RBC) membrane disorder, can be abrogated or markedly reduced by splenectomy. However, concerns regarding risks from overwhelming infections after splenectomy have restricted its use, especially in children. This study was designed to determine if partial splenectomy can decrease the hemolytic rate while maintaining phagocytic function of the spleen. Partial splenectomy was performed in 11 children (age 2 to 13) with HS. The effect on hemolytic rate was assessed by comparing the presurgical and postsurgical values for hemoglobin, reticulocyte number, and RBC life span. The residual splenic phagocytic function was assessed using technetium 99m scans and by enumerating the percentage of pitted RBCs in circulation. There were no complications from the surgical procedure in any of the 11 individuals. Following partial splenectomy, hemoglobin increased on the average by 3 g/dL, reticulocyte count decreased by 300 x 10(6)/L, and RBC life span was substantially prolonged. Normal technetium uptake was noted in the splenic remnant and the percentage of pitted RBCs was in the normal range. Partial splenectomy is effective in decreasing the hemolytic rate while maintaining residual splenic phagocytic function of the spleen in HS. We conclude that the use of this procedure as treatment for RBC membrane disorders warrants consideration, especially in infants under 5 years of age who need frequent transfusions.

scholarly journals Biotherapic of Trypanosoma cruzi 17d increases apoptosis in experimentally infected mice

2021 ◽  
Vol 10 (36) ◽  
pp. 119-124
Author(s):  
Patrícia Flora Sandri ◽  
Gislaine Janaina Sanchez Falkowski ◽  
Luzmarina Hernandes ◽  
Márcia Machado de Oliveira Dalálio ◽  
Denise Lessa Aleixo ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Controlled Trial ◽  
Basic Research ◽  
Treated Group ◽  
Oral Route ◽  
Control Group ◽  
Phagocytic Cells ◽  
Number Of Cells

Introduction: the mechanism of action of ultradiluted medicines has not yet been established[1,3]. Many basic research studies have focused on isopathic models using in vitro or in vivo designs [4,5]. Recent studies indicate that an ultradiluted (isopathic) antigen can transfer signals to the immune system and modulate its response when an organism is challenged against this same antigen [6]. Some studies on experimental infection of mice by T. cruzi identified apoptotic cells and showed that the increase of their number is associated with an increase also in the number of parasites in the blood of the infected animals, while blockage of apoptosis can be the target of therapeutic intervention [7,8]. Aim: to evaluate the development of apoptosis in mice treated with biotherapic of Trypanosoma cruzi in dilution 17d through in situ detection of fragmented DNA. Method: in a blind randomized controlled trial, 36 male Swiss mice age 4 or 8 weeks were distributed in groups control - treated with 7% hydroalcoholic solution(CI-4=9 animals or CI-8=9 animals); and treated with biotherapic 17d (BIOT-4=9 animals or BIOT-8=9 animals). Infection was performed with 1,400 trypomastigotes T. cruzi-strain Y via intraperitoneal. Biotherapic 17d was prepared through the addition of 0.9ml of concentrated T. cruzi (10E+7 trypomastigotes/ml) to 9.1 ml of distilled water. The following dilutions were prepared in 86% hydroalcoholic solution until dilution 16d. Dilution 17d was prepared with 7% hydroalcoholic solution. It was performed microbiological control and biological risk in vivo. Treatment: 0.2 ml in 3 consecutive days, oral route, from the moment infection was verified. Animals were sacrificed on the 3rd day of treatment in a chamber saturated with ether. The liver and spleen were removed and fixated in 4% paraformaldehyde for 24 hours and then included in paraffin. Apoptosis was evaluated through DNA fragmentation – TUNEL technique (TdT dUTP-biotin Nick End Labeling (ApopTag® Peroxidade-Chemicon). For statistical analysis software Statistica 8.0 was used. This study was approved by the Ethics Committee for Animal Experimentation of UEM. Results and Discussion: in the samples of liver of animals age 4 and 8 weeks either treated or not with biotherapic 17d it was found cells parasitized by amastigotes of T. cruzi with apoptotic bodies, or phagocytic cells with phagocytic vacuole with apoptotic marked material inside them. The number of cells in apoptosis in animals age 4 weeks was not significantly (p=0.03) larger in treated group BIOT-C4 than in control group CI-4 (Figure 1). In animals age 8 weeks, the number of cells in apoptosis was significantly (p

scholarly journals Initial assessment of the beneficial effect of partial splenectomy in hereditary spherocytosis

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2014-2020 ◽  
Author(s):  
G Tchernia ◽  
F Gauthier ◽  
F Mielot ◽  
JP Dommergues ◽  
J Yvart ◽  
...  
Keyword(s):  
Life Span ◽  
Hereditary Spherocytosis ◽  
Reticulocyte Count ◽  
Clinical Manifestations ◽  
Partial Splenectomy ◽  
Initial Assessment ◽  
Phagocytic Function ◽  
Normal Range ◽  
Rbc Membrane ◽  
Technetium Uptake

Abstract Clinical manifestations of hereditary spherocytosis (HS), the most common red blood cell (RBC) membrane disorder, can be abrogated or markedly reduced by splenectomy. However, concerns regarding risks from overwhelming infections after splenectomy have restricted its use, especially in children. This study was designed to determine if partial splenectomy can decrease the hemolytic rate while maintaining phagocytic function of the spleen. Partial splenectomy was performed in 11 children (age 2 to 13) with HS. The effect on hemolytic rate was assessed by comparing the presurgical and postsurgical values for hemoglobin, reticulocyte number, and RBC life span. The residual splenic phagocytic function was assessed using technetium 99m scans and by enumerating the percentage of pitted RBCs in circulation. There were no complications from the surgical procedure in any of the 11 individuals. Following partial splenectomy, hemoglobin increased on the average by 3 g/dL, reticulocyte count decreased by 300 x 10(6)/L, and RBC life span was substantially prolonged. Normal technetium uptake was noted in the splenic remnant and the percentage of pitted RBCs was in the normal range. Partial splenectomy is effective in decreasing the hemolytic rate while maintaining residual splenic phagocytic function of the spleen in HS. We conclude that the use of this procedure as treatment for RBC membrane disorders warrants consideration, especially in infants under 5 years of age who need frequent transfusions.

scholarly journals Saturated Fatty Acid Intake Is Associated With Increased Inflammation, Conversion of Kynurenine to Tryptophan, and Delta-9 Desaturase Activity in Healthy Humans

2020 ◽  
Vol 13 ◽  
pp. 117864692098194
Author(s):  
Jade Berg ◽  
Neda Seyedsadjadi ◽  
Ross Grant
Keyword(s):  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Desaturase Activity ◽  
Saturated Fat ◽  
Positive Association ◽  
Monounsaturated Fatty Acids ◽  
Healthy Humans ◽  
Rbc Membrane ◽  
Δ9 Desaturase ◽  
Tnf Α

Saturated fat ingestion has previously been linked to increases in inflammation. However the relationship between saturated fatty acid (SFA) intake and the kynureine:tryptophan ratio ([Kyn]:[Trp]), a marker of inflammation, has not been previously investigated. This study evaluated in healthy, middle aged, individuals (men = 48, women = 52), potential relationships between SFA intake, red blood cell (RBC) membrane SFAs and monounsaturated fatty acids (MUFA), the [Kyn]:[Trp] ratio, C-reactive protein (CRP), TNF-α and Δ9 desaturase activity. [Kyn]:[Trp] was positively associated with increases in Total fat ( P = .034) intake, including Total SFA ( P = .029) and Total MUFA ( P = .042) intakes. Unexpectedly the [Kyn]:[Trp] ratio was inversely associated with the percentage of Total SFA ( P = .004) and positively associated with percentage of Total MUFA ( P = .012) present in the RBC membrane. We found a positive association between Δ9 desaturase activity, responsible for the desaturation of a various SFAs to MUFAs, and [Kyn]:[Trp] ( P = .008). [Kyn]:[Trp] was also positively associated with CRP ( P = .044), however no significant relationship between [Kyn]:[Trp] and TNF-α was found. This study shows for the first time that SFA consumption increases inflammatory pathways linked to increased tryptophan to kynurenine conversion, even in healthy humans. Our data also suggests that SFA linked increases in inflammation occur concomitantly with an upregulation of Δ9 desaturase activity resulting in increased desaturation of SFA substrates to their MUFA derivatives.

scholarly journals Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells

2021 ◽  
Vol 17 (2) ◽  
pp. e1009259
Author(s):  
Merryn Fraser ◽  
Weidong Jing ◽  
Stefan Bröer ◽  
Florian Kurth ◽  
Leif-Erik Sander ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Fluorescent Dyes ◽  
Host Immune System ◽  
Enzymatic Reactions ◽  
Membrane Asymmetry ◽  
Outer Leaflet ◽  
Rbc Membrane ◽  
Infected Rbcs ◽  
Underlying Causes

The human malaria parasite Plasmodium falciparum relies on lipids to survive; this makes its lipid metabolism an attractive drug target. The lipid phosphatidylserine (PS) is usually confined to the inner leaflet of the red blood cell membrane (RBC) bilayer; however, some studies suggest that infection with the intracellular parasite results in the presence of this lipid in the RBC membrane outer leaflet, where it could act as a recognition signal to phagocytes. Here, we used fluorescent lipid analogues and probes to investigate the enzymatic reactions responsible for maintaining asymmetry between membrane leaflets, and found that in parasitised RBCs the maintenance of membrane asymmetry was partly disrupted, and PS was increased in the outer leaflet. We examined the underlying causes for the differences between uninfected and infected RBCs using fluorescent dyes and probes, and found that calcium levels increased in the infected RBC cytoplasm, whereas membrane cholesterol was depleted from the erythrocyte plasma membrane. We explored the resulting effect of PS exposure on enhanced phagocytosis by monocytes, and show that infected RBCs must expend energy to limit phagocyte recognition, and provide experimental evidence that PS exposure contributes to phagocytic recognition of P. falciparum-infected RBCs. Together, these findings underscore the pivotal role for PS exposure on the surface of Plasmodium falciparum-infected erythrocytes for in vivo interactions with the host immune system, and provide a rationale for targeted antimalarial drug design.

scholarly journals Damages at the nanoscale on red blood cells promoted by fire corals

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana R. Díaz-Marrero ◽  
Miriam C. Rodríguez González ◽  
Alberto Hernández Creus ◽  
Adriana Rodríguez Hernández ◽  
José J. Fernández
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Structural Damage ◽  
Defense Mechanism ◽  
Force Microscopy ◽  
Outer Leaflet ◽  
Rbc Membrane ◽  
Protein Toxins ◽  
Secondary Mechanism ◽  
Pore Forming Proteins

Abstract The hydrocoral Millepora alcicornis, known as fire coral, biosynthesize protein toxins with phospholipase A2 (PLA2) activity as a main defense mechanism; proteins that rapidly catalyse the hydrolysis at the sn-2 position of phosphatidylcholine-type phospholipids of cellular membranes. This hydrolysis mechanism triggers a structural damage in the outer leaflet of the red blood cells (RBC) membrane, by generating pores in the lipid bilayer that leads to a depletion of the cellular content of the damaged cell. A secondary mechanism, tentatively caused by pore-forming proteins toxins (PFTs), has been observed. The use of atomic force microscopy (AFM) has allowed to visualize the evolution of damages produced on the surface of the cells at the nanoscale level along the time.

scholarly journals Pulmonary Effects Due to Physical Exercise in Polluted Air: Evidence from Studies Conducted on Healthy Humans

2021 ◽  
Vol 11 (7) ◽  
pp. 2890
Author(s):  
Oscar F. Araneda ◽  
Franz Kosche-Cárcamo ◽  
Humberto Verdugo-Marchese ◽  
Marcelo Tuesta
Keyword(s):  
Physical Activity ◽  
Air Quality ◽  
Health Risks ◽  
Physical Inactivity ◽  
Basic Research ◽  
Private Institutions ◽  
Healthy Humans ◽  
The Cost ◽  
Rational Practice

Physical inactivity has caused serious effects on the health of the population, having an impact on the quality of life and the cost of healthcare for many countries. This has motivated government and private institutions to promote regular physical activity, which, paradoxically, can involve health risks when it is carried out in areas with poor air quality. This review collects information from studies conducted on healthy humans related to the pulmonary effects caused by the practice of physical activity when there is poor air quality. In addition, several challenges related to the technological and educational areas, as well as to applied and basic research, have been identified to facilitate the rational practice of exercise in poor air quality conditions.

scholarly journals On the definition of the healthiest body weight for children and adults

2014 ◽  
pp. 103-112
Author(s):  
Antonello Lorenzini
Keyword(s):  
Body Weight ◽  
Life Span ◽  
Basic Research ◽  
Epidemiological Data ◽  
Laboratory Animals ◽  
Public Health Issue ◽  
Important Public Health ◽  
Increased Risk ◽  
Correct Weight ◽  
Definition Of

Ongoing changes in societies are driving an expanding fraction of the world’s population towards a sedentary and overfed lifestyle. An overwhelming amount of data has linked increased body weight with an increased risk of acquiring a number of major diseases. Gerontologists, in order to extend the life span of laboratory animals, have used caloric restriction successfully for decades. This basic research on animals along with epidemiological data taken from vast human cohorts is cumulatively indicating that reducing one’s body weight should be part of the strategy to increase health and life span while reducing pathologies. What is not a trivial matter is defining the correct weight for each individual. This mini review raises some discussion points regarding this important public health issue.

scholarly journals Effects of age-dependent membrane transport changes on the homeostasis of senescent human red blood cells

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1334-1342 ◽  
Author(s):  
Virgilio L. Lew ◽  
Nuala Daw ◽  
Zipora Etzion ◽  
Teresa Tiffert ◽  
Adaeze Muoma ◽  
...  
Keyword(s):  
Membrane Transport ◽  
Inverse Correlation ◽  
Low Density ◽  
Hb A1c ◽  
Human Red Blood Cells ◽  
Rbc Membrane ◽  
Age Related ◽  
Cation Permeability ◽  
Powerful Activator ◽  
Permeability Increase

Abstract Little is known about age-related changes in red blood cell (RBC) membrane transport and homeostasis. We investigated first whether the known large variation in plasma membrane Ca2+ (PMCA) pump activity was correlated with RBC age. Glycated hemoglobin, Hb A1c, was used as a reliable age marker for normal RBCs. We found an inverse correlation between PMCA strength and Hb A1c content, indicating that PMCA activity declines monotonically with RBC age. The previously described subpopulation of high-Na+, low-density RBCs had the highest Hb A1c levels, suggesting it represents a late homeostatic condition of senescent RBCs. Thus, the normal densification process of RBCs with age must undergo late reversal, requiring a membrane permeability increase with net NaCl gain exceeding KCl loss. Activation of a nonselective cation channel, Pcat, was considered the key link in this density reversal. Investigation of Pcat properties showed that its most powerful activator was increased intracellular Ca2+. Pcat was comparably selective to Na+, K+, choline, and N-methyl-D-glucamine, indicating a fairly large, poorly selective cation permeability pathway. Based on these observations, a working hypothesis is proposed to explain the mechanism of progressive RBC densification with age and of the late reversal to a low-density condition with altered ionic gradients.

scholarly journals Long-term culture and cloning of primary human bronchial basal cells that maintain multipotent differentiation capacity and CFTR channel function

2018 ◽  
Vol 315 (2) ◽  
pp. L313-L327 ◽  
Author(s):  
Jennifer R. Peters-Hall ◽  
Melissa L. Coquelin ◽  
Michael J. Torres ◽  
Ryan LaRanger ◽  
Busola R. Alabi ◽  
...  
Keyword(s):  
Life Span ◽  
Genome Editing ◽  
Basic Research ◽  
Bronchial Epithelial Cell ◽  
Basal Cells ◽  
Rock Inhibitor ◽  
Bronchial Epithelial ◽  
Differentiation Capacity ◽  
Multipotent Differentiation

While primary cystic fibrosis (CF) and non-CF human bronchial epithelial basal cells (HBECs) accurately represent in vivo phenotypes, one barrier to their wider use has been a limited ability to clone and expand cells in sufficient numbers to produce rare genotypes using genome-editing tools. Recently, conditional reprogramming of cells (CRC) with a Rho-associated protein kinase (ROCK) inhibitor and culture on an irradiated fibroblast feeder layer resulted in extension of the life span of HBECs, but differentiation capacity and CF transmembrane conductance regulator (CFTR) function decreased as a function of passage. This report details modifications to the standard HBEC CRC protocol (Mod CRC), including the use of bronchial epithelial cell growth medium, instead of F medium, and 2% O2, instead of 21% O2, that extend HBEC life span while preserving multipotent differentiation capacity and CFTR function. Critically, Mod CRC conditions support clonal growth of primary HBECs from a single cell, and the resulting clonal HBEC population maintains multipotent differentiation capacity, including CFTR function, permitting gene editing of these cells. As a proof-of-concept, CRISPR/Cas9 genome editing and cloning were used to introduce insertions/deletions in CFTR exon 11. Mod CRC conditions overcome many barriers to the expanded use of HBECs for basic research and drug screens. Importantly, Mod CRC conditions support the creation of isogenic cell lines in which CFTR is mutant or wild-type in the same genetic background with no history of CF to enable determination of the primary defects of mutant CFTR.

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