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Article ; Online: Endoplasmic Reticulum Stress, a Driver or an Innocent Bystander in Endothelial Dysfunction Associated with Hypertension?

Cunard, Robyn

2017 Volume 19, Issue 8, Page(s) 64

Abstract: Purpose of review: Hypertension (htn) is a polygenic disorder that effects up to one third of the US population. The endoplasmic reticulum (ER) stress response is a homeostatic pathway that regulates membrane structure, protein folding, and secretory ... ...

Abstract	Purpose of review: Hypertension (htn) is a polygenic disorder that effects up to one third of the US population. The endoplasmic reticulum (ER) stress response is a homeostatic pathway that regulates membrane structure, protein folding, and secretory function. Emerging evidence suggests that ER stress may induce endothelial dysfunction; however, it is unclear whether ER stress-associated endothelial dysfunction modulates htn. Recent findings: Exogenous and endogenous molecules activate ER stress in the endothelium, and ER stress mediates some forms of neurogenic htn, such as angiotensin II-dependent htn. Human studies suggest that ER stress induces endothelial dysfunction, though direct evidence that ER stress augments blood pressure in humans is lacking. However, animal and cellular models demonstrate direct evidence that ER stress influences htn. ER stress is likely one of many players in a complex interplay among molecular pathways that influence the expression of htn. Targeted activation of specific ER stress pathways may provide novel therapeutic opportunities.
Language	English
Publishing date	2017-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-017-0762-x
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Zs.A 5522: Show issues

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Article ; Online: Therapeutic plasma exchange in the intensive care unit: Rationale, special considerations, and techniques for combined circuits.

Sanchez, Amber P / Ward, David M / Cunard, Robyn

Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy

2022

Abstract: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique with proven efficacy in a variety of conditions, including in the intensive care setting. It is not uncommon for a critically ill patient to require more than one ... ...

Abstract	Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique with proven efficacy in a variety of conditions, including in the intensive care setting. It is not uncommon for a critically ill patient to require more than one extracorporeal procedure in addition to TPE. This review focuses on the combination of TPE with other extracorporeal circuits in a critical care setting via a single vascular access (either in-series, parallel, or a hybrid mode) which is often referred to as performing procedures "in tandem." Authors performed literature review via pubmed.gov using search terms: plasma exchange, plasmapheresis, apheresis, tandem circuits, combined circuits, critical care, ICU, CRRT, hemodialysis, and ECMO. Thirty-eight English-language, peer-reviewed papers were appraised that satisfied the content of this review on techniques for combining circuits with plasma exchange, as well as describing the advantages of tandem procedures and potential complications that can arise. Performing these procedures simultaneously can be advantageous in reducing total procedure and staffing time, avoiding placement of additional central lines, reducing overall need for anticoagulation, and limiting multiple blood primes in certain populations. However, the described combined circuits are complex, associated with higher complications, and require a skilled team to understand and mitigate the potential complications associated with these combined procedures.
Language	English
Publishing date	2022-12-05
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2119809-3
ISSN	1744-9987 ; 1091-6660 ; 1744-9979
ISSN (online)	1744-9987
ISSN	1091-6660 ; 1744-9979
DOI	10.1111/1744-9987.13814
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Zs.A 5208: Show issues

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Article: Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.

Cunard, Robyn

Journal of clinical medicine

2015 Volume 4, Issue 4, Page(s) 715–740

Abstract: Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed ...

Abstract	Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy.
Language	English
Publishing date	2015-04-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm4040715
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Article: Mammalian tribbles homologs at the crossroads of endoplasmic reticulum stress and Mammalian target of rapamycin pathways.

Cunard, Robyn

Scientifica

2013 Volume 2013, Page(s) 750871

Abstract: In 2000, investigators discovered Tribbles, a Drosophila protein that coordinates morphogenesis by inhibiting mitosis. Further work has delineated Xenopus (Xtrb2), Nematode (Nipi-3), and mammalian homologs of Drosophila tribbles, which include TRB1, TRB2, ...

Abstract	In 2000, investigators discovered Tribbles, a Drosophila protein that coordinates morphogenesis by inhibiting mitosis. Further work has delineated Xenopus (Xtrb2), Nematode (Nipi-3), and mammalian homologs of Drosophila tribbles, which include TRB1, TRB2, and TRB3. The sequences of tribbles homologs are highly conserved, and despite their protein kinase structure, to date they have not been shown to have kinase activity. TRB family members play a role in the differentiation of macrophages, lymphocytes, muscle cells, adipocytes, and osteoblasts. TRB isoforms also coordinate a number of critical cellular processes including glucose and lipid metabolism, inflammation, cellular stress, survival, apoptosis, and tumorigenesis. TRB family members modulate multiple complex signaling networks including mitogen activated protein kinase cascades, protein kinase B/AKT signaling, mammalian target of rapamycin, and inflammatory pathways. The following review will discuss metazoan homologs of Drosophila tribbles, their structure, expression patterns, and functions. In particular, we will focus on TRB3 function in the kidney in podocytes. This review will also discuss the key signaling pathways with which tribbles proteins interact and provide a rationale for developing novel therapeutics that exploit these interactions to provide better treatment options for both acute and chronic kidney disease.
Language	English
Publishing date	2013-12-30
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2672321-9
ISSN	2090-908X
ISSN	2090-908X
DOI	10.1155/2013/750871
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Article ; Online: Anaphylaxis From Ethylene Oxide-Sterilized Dialysis Tubing and Needles: A Case Report.

Crane, Clarkson / Cunard, Robyn A / Sweiss, Natalie / Scanlon, Nicholas / Doherty, Taylor A / Potok, O Alison

American journal of kidney diseases : the official journal of the National Kidney Foundation

2023 Volume 82, Issue 2, Page(s) 243–246

Abstract: Hypersensitivity reactions to ethylene oxide-sterilized dialyzers have been well described. Although ethylene oxide is no longer used to sterilize most dialyzers, it is used on other pieces of dialysis equipment. We present a case of a 78-year-old man ... ...

Abstract	Hypersensitivity reactions to ethylene oxide-sterilized dialyzers have been well described. Although ethylene oxide is no longer used to sterilize most dialyzers, it is used on other pieces of dialysis equipment. We present a case of a 78-year-old man who experienced dialysis-related anaphylaxis attributed to an IgE-mediated allergy to dialysis tubing and needles sterilized with ethylene oxide. Shortly after transitioning from a tunneled catheter to an arteriovenous fistula, he developed multiple episodes of intradialytic hypotension and syncope within minutes of starting dialysis. Laboratory evaluation revealed marked leukocytosis, eosinophilia, and elevated anti-ethylene oxide IgE antibody. After pretreatment with corticosteroids and antihistamines, the rinsing of dialysis tubing, and transition of access back to a tunneled catheter, he tolerated subsequent dialysis treatments. Review of his history revealed chronic eosinophilia since the time of hemodialysis initiation. We hypothesize his eosinophilia and mast cell degranulation began upon initial exposure to ethylene oxide and hemodialysis equipment. When use of the arteriovenous fistula was resumed, he was exposed to a higher "dose" of ethylene oxide due to the use of needles. The higher antigenic stimuli triggered a memory immune response, leading to mast cell degranulation and repeated anaphylactic episodes that were overcome by minimization of ethylene oxide-sterilized equipment, corticosteroid pretreatment, and the anti-IgE Fc monoclonal omalizumab.
MeSH term(s)	Male ; Humans ; Aged ; Renal Dialysis/adverse effects ; Anaphylaxis/etiology ; Needles/adverse effects ; Ethylene Oxide/adverse effects ; Immunoglobulin E ; Eosinophilia/complications ; Oxides
Chemical Substances	Ethylene Oxide (JJH7GNN18P) ; Immunoglobulin E (37341-29-0) ; Oxides
Language	English
Publishing date	2023-01-21
Publishing country	United States
Document type	Case Reports ; Research Support, N.I.H., Extramural
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2022.12.004
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Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 468: Show issues

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Article ; Online: Comprehensive guide to managing a chronic automated red cell exchange program in sickle cell disease.

Cunard, Robyn / Gopal, Srila / Kopko, Patricia M / Dang, Minh-Uyen / Hazle, Kathryn M / Sanchez, Amber P

Journal of clinical apheresis

2022 Volume 37, Issue 5, Page(s) 497–506

Abstract: Sickle cell disease (SCD) is associated with significant morbidity and mortality, and limits both the quality and quantity of life. Transfusion therapy, specifically automated red cell exchange (aRCE), plays a key role in management of SCD and is ... ...

Abstract	Sickle cell disease (SCD) is associated with significant morbidity and mortality, and limits both the quality and quantity of life. Transfusion therapy, specifically automated red cell exchange (aRCE), plays a key role in management of SCD and is beneficial for certain indications in the chronic, outpatient setting. The approach to maintain a successful chronic aRCE program for SCD is multifaceted. This review will highlight important considerations including indications for aRCE, patient selection, transfusion medicine pearls, vascular access needs, complications of therapy, aRCE prescription, and therapy optimization. Moreover, the importance of a multidisciplinary approach with frequent communication between the services involved cannot be overstated. Ultimately, the underlying goal of a chronic RCE program is to improve the quality of life and longevity of patients with SCD.
MeSH term(s)	Anemia, Sickle Cell/therapy ; Erythrocyte Transfusion ; Graft vs Host Disease ; Humans ; Quality of Life
Language	English
Publishing date	2022-09-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604912-6
ISSN	1098-1101 ; 0733-2459
ISSN (online)	1098-1101
ISSN	0733-2459
DOI	10.1002/jca.22014
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Zs.A 1831: Show issues

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Article: The potential use of PPARalpha agonists as immunosuppressive agents.

Cunard, Robyn

Current opinion in investigational drugs (London, England : 2000)

2005 Volume 6, Issue 5, Page(s) 467–472

Abstract: Fibrates are peroxisome proliferator-activated receptor (PPAR)alpha ligands that have been used to treat hyperlipidemia and atherosclerosis for many years, and research has demonstrated that these agents have immunosuppressive effects. PPARalpha is ... ...

Abstract	Fibrates are peroxisome proliferator-activated receptor (PPAR)alpha ligands that have been used to treat hyperlipidemia and atherosclerosis for many years, and research has demonstrated that these agents have immunosuppressive effects. PPARalpha is expressed in multiple inflammatory cell types, and its ligands abrogate expression of inflammatory diseases. This review focuses on the use of fibrates in inflammatory disease models. It also describes proposed mechanisms of action of PPARalpha ligands and discusses the potential use of these medications as immunosuppressive agents.
MeSH term(s)	Animals ; Clofibric Acid/immunology ; Clofibric Acid/pharmacology ; Clofibric Acid/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; PPAR alpha/agonists ; PPAR alpha/immunology ; PPAR alpha/therapeutic use
Chemical Substances	Immunosuppressive Agents ; PPAR alpha ; Clofibric Acid (53PF01Q249)
Language	English
Publishing date	2005-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2027913-9
ISSN	2040-3429 ; 1472-4472 ; 0967-8298
ISSN (online)	2040-3429
ISSN	1472-4472 ; 0967-8298
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Zs.A 5305: Show issues

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Article ; Online: The endoplasmic reticulum stress response and diabetic kidney disease.

Cunard, Robyn / Sharma, Kumar

American journal of physiology. Renal physiology

2011 Volume 300, Issue 5, Page(s) F1054–61

Abstract: The endoplasmic reticulum (ER) folds and modifies proteins; however, during conditions of cellular stress, unfolded proteins accumulate in the ER and activate the unfolded protein response (UPR). The UPR, also referred to as the ER stress response, ... ...

Abstract	The endoplasmic reticulum (ER) folds and modifies proteins; however, during conditions of cellular stress, unfolded proteins accumulate in the ER and activate the unfolded protein response (UPR). The UPR, also referred to as the ER stress response, activates three distinct signaling cascades that are designed to globally reduce transcription and translation. The three major arms of the mammalian UPR include 1) protein kinase RNA (PKR)-like ER kinase (PERK), 2) inositol-requiring protein-1 (IRE1α), and 3) activating transcription factor-6 (ATF6) pathways. The PERK pathway rapidly attenuates protein translation, whereas the ATF6 and IRE1α cascades transcriptionally upregulate ER chaperone genes that promote proper folding and ER-associated degradation (ERAD) of proteins. This integrated response in turn allows the folding machinery of the ER to catch up with the backlog of unfolded proteins. The ER stress response plays a role in a number of pathophysiological processes, including pancreatic β-cell failure and apoptosis. The goals of the current review are to familiarize investigators with cellular and tissue activation of this response in the rodent and human diabetic kidney. Additionally, we will review therapeutic modulators of the ER stress response and discuss their efficacy in models of diabetic kidney disease. The ER stress response has both protective and deleterious features. A better understanding of the molecular pathways regulated during this process in a cell- and disease-specific manner could reveal novel therapeutic strategies in chronic renal diseases, including diabetic kidney disease.
MeSH term(s)	Animals ; Cytoprotection ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/physiopathology ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; Humans ; Kidney/drug effects ; Kidney/metabolism ; Kidney/physiopathology ; Signal Transduction ; Stress, Physiological ; Unfolded Protein Response
Language	English
Publishing date	2011-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00021.2011
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Article ; Online: Extracorporeal photopheresis for the treatment of chronic graft versus host disease.

Kansu, Emin / Ward, David / Sanchez, Amber P / Cunard, Robyn / Hayran, Mutlu / Huseyin, Beril / Vaughan, Majella / Ku, Grace / Curtin, Peter / Mulroney, Carolyn / Costello, Caitlin / Castro, Januario E / Wieduwilt, Matthew / Corringham, Sue / Ihasz-Davis, Anita / Nelson, Connie / Ball, Edward D

Hematology (Amsterdam, Netherlands)

2022 Volume 27, Issue 1, Page(s) 785–794

Abstract: Objectives: Chronic graft versus host disease (chronic GVHD) still remains the leading cause of late morbidity and mortality for allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. In this retrospective study, 53 consecutive allo-HSCT ... ...

Abstract	Objectives: Chronic graft versus host disease (chronic GVHD) still remains the leading cause of late morbidity and mortality for allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. In this retrospective study, 53 consecutive allo-HSCT patients with chronic GVHD refractory to corticosteroids were treated with extracorporeal photopheresis (ECP). Methods: This study was performed as a retrospective single-center study. Medical records of a total of 59 patients treated with ECP for chronic GVHD were reviewed. Results: Best organ responses to ECP were observed in skin, mouth mucosa, eyes and liver. Overall response rate (ORR) to ECP was 81.2% (CR 17% and PR 64.2%). Overall survival (OS) was 84.9% and 36.7%, at 1 and 3 years, respectively. Female sex appears to have an advantage on ORR. Patients achieving ORR were able to maintain their responses with a prolonged continuation of treatments for +6 and +12 months indicating the benefits of longer ECP treatment. Discussion: We found that patients with chronic GVHD who were treated with ECP for 12 months or longer had a higher response rate. Our findings in line with the data reported previously suggest that patients responding to ECP should continue longer therapy schedules to achieve a better and sustained response. In our cohort, long-term ECP therapy was safe and well-tolerated with no significant adverse effects. Best responses were observed in the patients with skin, eye, liver and oral involvement. The ECP procedure offers the advantage relative to the problems with typical immunosuppressive agents. The female sex appeared to have an advantage based on the cumulative probability of the OR after ECP for chronic GVHD.
MeSH term(s)	Chronic Disease ; Female ; Graft vs Host Disease/etiology ; Graft vs Host Disease/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Photopheresis/adverse effects ; Photopheresis/methods ; Retrospective Studies ; Transplantation, Homologous/adverse effects
Language	English
Publishing date	2022-07-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1341428-8
ISSN	1607-8454 ; 1024-5332 ; 1024-5340
ISSN (online)	1607-8454
ISSN	1024-5332 ; 1024-5340
DOI	10.1080/16078454.2022.2095884
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Zs.A 4538: Show issues

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Article ; Online: The selective therapeutic apheresis procedures.

Sanchez, Amber P / Cunard, Robyn / Ward, David M

Journal of clinical apheresis

2013 Volume 28, Issue 1, Page(s) 20–29

Abstract: Selective apheresis procedures have been developed to target specific molecules, antibodies, or cellular elements in a variety of diseases. The advantage of the selective apheresis procedures over conventional therapeutic plasmapheresis is preservation ... ...

Abstract	Selective apheresis procedures have been developed to target specific molecules, antibodies, or cellular elements in a variety of diseases. The advantage of the selective apheresis procedures over conventional therapeutic plasmapheresis is preservation of other essential plasma components such as albumin, immunoglobulins, and clotting factors. These procedures are more commonly employed in Europe and Japan, and few are available in the USA. Apheresis procedures discussed in this review include the various technologies available for low-density lipoprotein (LDL) apheresis, double filtration plasmapheresis (DFPP), cryofiltration, immunoadsorption procedures, adsorption resins that process plasma, extracorporeal photopheresis, and leukocyte apheresis.
MeSH term(s)	Autoantibodies/blood ; Blood Cells ; Blood Component Removal/instrumentation ; Blood Component Removal/methods ; Cryoglobulins ; Filtration/instrumentation ; Filtration/methods ; Humans ; Immobilized Proteins ; Immunoglobulins/blood ; Immunosorbent Techniques/instrumentation ; Lipids/blood ; Lipoproteins/blood ; Photopheresis/instrumentation ; Photopheresis/methods ; Resins, Synthetic ; Staphylococcal Protein A ; United States
Chemical Substances	Autoantibodies ; Cryoglobulins ; Immobilized Proteins ; Immunoglobulins ; Lipids ; Lipoproteins ; Resins, Synthetic ; Staphylococcal Protein A
Language	English
Publishing date	2013-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604912-6
ISSN	1098-1101 ; 0733-2459
ISSN (online)	1098-1101
ISSN	0733-2459
DOI	10.1002/jca.21265
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