scholarly journals Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Martin Sauer ◽  
Jens Altrichter ◽  
Cristof Haubner ◽  
Annette Pertschy ◽  
Thomas Wild ◽  
...  

Purpose.Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies.Methods and Patients.Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity.Results.The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors.Conclusion.The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip Newsholme

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.


2020 ◽  
Vol 401 (8) ◽  
pp. 933-943 ◽  
Author(s):  
Stephen L. Nutt ◽  
Christine Keenan ◽  
Michaël Chopin ◽  
Rhys S. Allan

AbstractThe polycomb repressive complex 2 (PRC2) consists of three core components EZH2, SUZ12 and EED. EZH2 catalyzes the methylation of lysine 27 of histone H3, a modification associated with gene silencing. Through gene duplication higher vertebrate genomes also encode a second partially redundant methyltransferase, EZH1. Within the mammalian immune system most research has concentrated on EZH2 which is expressed predominantly in proliferating cells. EZH2 and other PRC2 components are required for hematopoietic stem cell function and lymphocyte development, at least in part by repressing cell cycle inhibitors. At later stages of immune cell differentiation, EZH2 plays essential roles in humoral and cell-mediated adaptive immunity, as well as the maintenance of immune homeostasis. EZH2 is often overactive in cancers, through both gain-of-function mutations and over-expression, an observation that has led to the development and clinical testing of specific EZH2 inhibitors. Such inhibitors may also be of use in inflammatory and autoimmune settings, as EZH2 inhibition dampens the immune response. Here, we will review the current state of understanding of the roles for EZH2, and PRC2 more generally, in the development and function of the immune system.


1984 ◽  
Vol 246 (5) ◽  
pp. E405-E411 ◽  
Author(s):  
W. K. Ward ◽  
J. B. Halter ◽  
J. C. Beard ◽  
D. Porte

States of insulin resistance are characterized by hyperinsulinemia that often appears to be out of proportion to the minimal degree of hyperglycemia. One possible explanation for these findings is that mild hyperglycemia per se can cause an adaptive increase in islet sensitivity to glucose, leading to increased insulin output at a given glucose level. To test this hypothesis, we compared acute insulin responses (AIR) and acute glucagon responses (AGR) to 5-g arginine injections before and after 20-h glucose infusions (200 mg X m-2 X min-1) in 11 healthy men of varying age and degree of adiposity. The 20-h glucose infusion caused an increase in fasting plasma glucose (PG) in all subjects (95 +/- 2 vs. 130 +/- 3 mg/dl). PG was clamped at three levels (approximately 95, 165, and 235 mg/dl) before and after the 20-h glucose infusion. Despite matching of PG levels, consistent increases of AIR were observed after the 20-h glucose infusion: 86 +/- 10 vs. 57 +/- 8 at PG = 95 (P = 0.002); 241 +/- 20 vs. 192 +/- 22 at PG = 165 (P = 0.02); and 508 +/- 59 vs. 380 +/- 50 microU/ml at PG = 235 mg/dl (P = 0.009). In addition, the slope of the relationship between AIR and PG level (potentiation slope), a measure of B cell sensitivity to glucose, increased consistently from 2.28 +/- 0.35 (control) to 3.07 +/- 0.45 (P = 0.004) after the 20-h infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


2006 ◽  
Vol 85 (12) ◽  
pp. 1061-1073 ◽  
Author(s):  
A. Jewett ◽  
C. Head ◽  
N.A. Cacalano

Mounting effective anti-tumor immune responses against tumors by both the innate and adaptive immune effectors is important for the clearance of tumors. However, accumulated evidence indicates that immune responses that should otherwise suppress or eliminate transformed cells are themselves suppressed by the function of tumor cells in a variety of cancer patients, including those with oral cancers. Signaling abnormalities, spontaneous apoptosis, and reduced proliferation and function of circulating natural killer cells (NK), T-cells, dendritic cells (DC), and tumor-infiltrating lymphocytes (TILs) have been documented previously in oral cancer patients. Several mechanisms have been proposed for the functional deficiencies of tumor-associated immune cells in oral cancer patients. Both soluble factors and contact-mediated immunosuppression by the tumor cells have been implicated in the inhibition of immune cell function and the progression of tumors. More recently, elevated levels and function of key transcription factors in tumor cells, particularly NFκB and STAT3, have been shown to mediate immune suppression in the tumor microenvironment. This review will focus on these emerging mechanisms of immunosuppression in oral cancers.


PEDIATRICS ◽  
1960 ◽  
Vol 26 (3) ◽  
pp. 452-453
Author(s):  
Mitchell I. Rubin

It May be appropriate to a pediatric audience in a consideration of cellular structure and function to quote from an old nursery rhyme, familiar to most of us: Little girls are made of Sugar and spice and all that's nice— And little boys are made of Frogs and snails and puppy dog tails. Actually, we know that this is not the case, and that little boys and girls are made of cells—millions and millions of them. The human infant at birth is said to contain 10 trillion cells. It, therefore, seems reasonable that prior to a discussion of the numerous diseases which affect children ("bundles of cells"), their nutritional and other requirements, that we consider a basic unit of life—the cell. To the medical student of a quarter of a century ago, and for many years thereafter, the study of the cell held little fascination. Structurally, it was recognized that there was a cell membrane which enclosed a cytoplasmic mass and nucleus, and there were structural substances such as mitochondria within the cytoplasm. The cell as a "chemical factory" was known to biologists, biochemists and geneticists for many years, but this knowledge had very limited influence on medical practice. Physicians thought more in terms of organ function, rather than cell function. This attitude has undergone striking change with the widespread therapeutic usage of vitamins, hormones (particularly the steroid hormones), antibiotics and antimetabolites in clinical medicine. With the recognition of the unity of nature, the biologic similarity between human cells and single-cell organisms and the biologic information gained in the study of single-cell organisms, there has been kindled a widespread and excited inquiry into the functions of the cells of humans.


Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1398
Author(s):  
Yanyu Huang ◽  
Hsiao-Chi Wang ◽  
Junwei Zhao ◽  
Ming-Heng Wu ◽  
Tsung-Chieh Shih

Evasion of immune surveillance is an accepted hallmark of tumor progression. The production of immune suppressive mediators by tumor cells is one of the major mechanisms of tumor immune escape. Galectin-1 (Gal-1), a pivotal immunosuppressive molecule, is expressed by many types of cancer. Tumor-secreted Gal-1 can bind to glycosylated receptors on immune cells and trigger the suppression of immune cell function in the tumor microenvironment, contributing to the immune evasion of tumors. The aim of this review is to summarize the current literature on the expression and function of Gal-1 in the human tumor microenvironment, as well as therapeutics targeting Gal-1.


2007 ◽  
Vol 26 (10) ◽  
pp. 817-821 ◽  
Author(s):  
Orlando Cesar de Oliveira Barretto ◽  
Karina Soeiro Prestes ◽  
Lorena Kessia Figueiredo Fonseca ◽  
Paulo Augusto Achucarro Silveira

Loxoscelism is the syndrome caused by the brown spider Loxosceles gaucho bite in humans. Its effect on erythrocytes has been studied in humans, rabbits, pigs and guinea pigs. In this study, the damage that the L gaucho spider venom causes to the structure and function of erythrocytes in vivo was investigated in rabbits. Before and after the rabbits were envenomed, membrane proteins were studied through polyacrylamide gel electrophoresis and membrane function was ascertained using the osmotic fragility test, together with the highly sensitive technique of ektacytometry. Six New Zealand rabbits were inoculated by intradermal injection into the dorsal region (10 μg of venom/kg of body weight in 0.2 mL of saline). Blood was collected at 24, 48, 72 and 120 h after inoculation. The membrane protein study did not reveal any alteration in their relative band concentrations, but the osmotic fragility test showed increased hemolysis in slightly hypotonic sodium chloride solutions (at 0.6 and 0.55%). In addition, the ektacytometer study revealed greater deformability to increasing shear stress on the order of 3—30 Pascals when compared with controls, showing that the L gaucho venom does in fact alter red cell function. Human & Experimental Toxicology (2007) 26 , 817— 821


Author(s):  
Jianying Li ◽  
Chelsea Bolyard ◽  
Gang Xin ◽  
Zihai Li

Tumor-infiltrating myeloid cells are a prominent pro-tumorigenic immune cell population that limit host anti-tumor immunity and present a significant obstacle for many cancer immunotherapies. Targeting the mechanisms regulating myeloid cell function within the tumor microenvironment may overcome immunotherapy resistance in some cancers. Recent discoveries in the emerging field of immunometabolism reveal that the metabolic profiles of intratumoral myeloid cells are rewired to adapt to the nutrition-limited tumor microenvironment, and this shapes their pro-tumor phenotypes. Interestingly, metabolic modulation can shift these myeloid cells toward the immune-stimulating anti-tumor phenotype. In this review, we will highlight the roles of specific metabolic pathways in the activation and function of myeloid cells, and discuss the therapeutic value of metabolically reprogramming myeloid cells to augment and improve outcomes with cancer immunotherapy.


Author(s):  
Philip Newsholme

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.


2019 ◽  
Vol 20 (8) ◽  
pp. 823-828 ◽  
Author(s):  
Songjie Cai ◽  
Jing Zhao ◽  
Takuya Ueno ◽  
Anil Chandraker

Siglecs are mammalian sialic acid (Sia) recognizing immuno-globulin-like receptors expressed across the major leukocyte lineages, and function to recognize ubiquitous Sia epitopes on the cell surface. Many Siglecs are inhibitory receptors expressed on innate immune cells, they also have a role in maintaining B cell tolerance as well as modulating the activation of conventional and plasmocytic dendritic cells. Through these and other roles they contribute directly and indirectly to the regulation of T cell function. Siglecs have been identified to play key roles in several forms of blood cancers, autoimmune and infection deceases. So far as we know, there’s no Siglecs related research works on solid organ transplantation. In this review, we describe our understanding of the potential roles of Siglecs in the regulation of immune cell function, which may be crosslinked to allo-rejection and ischemia-reperfusion injury.


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