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1.
Ann Biol Clin (Paris) ; 77(4): 439-445, 2019 08 01.
Article in French | MEDLINE | ID: mdl-31418706

ABSTRACT

A 67 years old woman with a Waldenström disease was admitted in the intensive care unit for dyspnea and fever. During hospitalization, episodes of undetectable glycemia were observed without any hypoglycemia symptoms. Plasma glucose was determined with the hexokinase method (recommended). From this observation, a literature review on PubMed was performed to investigate similar cases. In patients with protides in excess (e.g. immunoproliferative syndrome), absorption measurements could be disrupted by the precipitation of excess protein (IgM in most cases). Other parameters could be affected: bilirubin, phosphate, HDL cholesterol, GGT, CRP and calcemia. In our case, the main difficulty was to identify the cause of the interference and then correct it. Using a series of dilution, we prevented protide precipitation allowing correct glucose determination. Those interferences are rare, but present a real analytical difficulty. Biologists should be aware of those interferences because of dramatics consequences.


Subject(s)
Blood Chemical Analysis/methods , Blood Glucose/analysis , Hexokinase/metabolism , Hypoglycemia/diagnosis , Paraproteins/adverse effects , Waldenstrom Macroglobulinemia/blood , Aged , Artifacts , Blood Chemical Analysis/standards , Blood Glucose/metabolism , Diagnosis, Differential , Dyspnea/blood , Dyspnea/diagnosis , Dyspnea/etiology , False Positive Reactions , Female , Fever/blood , Fever/diagnosis , Fever/etiology , Hexokinase/chemistry , Humans , Hypoglycemia/blood , Paraproteins/metabolism , Retinal Hemorrhage/blood , Retinal Hemorrhage/diagnosis , Retinal Hemorrhage/etiology , Waldenstrom Macroglobulinemia/complications , Waldenstrom Macroglobulinemia/diagnosis
2.
Expert Opin Investig Drugs ; 28(7): 643-657, 2019 07.
Article in English | MEDLINE | ID: mdl-31165652

ABSTRACT

INTRODUCTION: Delayed graft function (DGF) has a significant impact on kidney transplantation outcome. One of the underlying pivotal mechanisms is organ preservation and associated hypothermia and biochemical alteration. AREAS COVERED: This paper focuses on organ preservation and its clinical consequences and describes 1. A comprehensive presentation of the pathophysiological mechanism involved in delayed graft function development; 2. The impact on endothelial cells and microvasculature integrity and the consequences on transplanted organ outcome; 3. The reassessment of dynamic organ preservation motivated by the growing use of extended criteria donors and the interest in the potential of normothermia; 4. The role of oxygenation during dynamic preservation; and 5. Novel oxygen carriers and their proof of concept in transplantation, among which M101 (HEMO2life®) is currently the most extensively investigated. EXPERT OPINION: Metabolic disturbances and imbalance of oxygen supply during preservation highlight the importance of providing oxygen. Normothermia, permitted by recent advances in machine perfusion technology, appears to be the leading edge of preservation technology. Several oxygen transporters are compatible with normothermia; however, only M101 also demonstrates compatibility with standard hypothermic preservation.


Subject(s)
Acute Kidney Injury/prevention & control , Kidney Transplantation/methods , Oxygen/metabolism , Animals , Delayed Graft Function/physiopathology , Endothelial Cells/metabolism , Humans , Hypothermia, Induced/methods , Organ Preservation/methods , Tissue Donors/supply & distribution
3.
Int J Mol Sci ; 20(9)2019 May 08.
Article in English | MEDLINE | ID: mdl-31071925

ABSTRACT

Current organ shortages have led centers to extend the acceptance criteria for organs, increasing the risk for adverse outcomes. Current preservation protocols have not been adapted so as to efficiently protect these organs. Herein, we target oxidative stress, the key mechanism of ischemia reperfusion injury. Vectisol® is a novel antioxidant strategy based on the encapsulation of resveratrol into a cyclodextrin, increasing its bioavailability. We tested this compound as an additive to the most popular static preservation solutions and machine perfusion (LifePort) in a preclinical pig model of kidney autotransplantation. In regard to static preservation, supplementation improved glomerular filtration and proximal tubular function early recovery. Extended follow-up confirmed the higher level of protection, slowing chronic loss of function (creatininemia and proteinuria) and the onset of histological lesions. Regarding machine perfusion, the use of Vectisol® decreased oxidative stress and apoptosis at the onset of reperfusion (30 min post declamping). Improved quality was confirmed with decreased early levels of circulating SOD (Superoxide Dismutase) and ASAT (asparagine amino transferase). Supplementation slowed the onset of chronic loss of function, as well as interstitial fibrosis and tubular atrophy. The simple addition of Vectisol® to the preservation solution significantly improved the performance of organ preservation, with long-term effects on the outcome. This strategy is thus a key player for future multi-drug therapy aimed at ischemia reperfusion in transplantation.


Subject(s)
Antioxidants/administration & dosage , Kidney Transplantation/adverse effects , Kidney/physiopathology , Resveratrol/chemistry , Transplantation, Autologous , Animals , Antioxidants/chemistry , Cyclodextrins/administration & dosage , Cyclodextrins/chemistry , Disease Models, Animal , Drug Compounding , Humans , Kidney/drug effects , Organ Preservation/methods , Oxidative Stress/drug effects , Reperfusion Injury/drug therapy , Reperfusion Injury/physiopathology , Resveratrol/administration & dosage , Solubility , Swine
4.
Expert Opin Ther Targets ; 23(6): 495-509, 2019 06.
Article in English | MEDLINE | ID: mdl-31022355

ABSTRACT

INTRODUCTION: Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians in a broad variety of clinical settings such as perioperative and intensive care. Renal IRI induced acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs. Areas covered: This paper focuses on the pathophysiology of transplantation-related AKI and recent findings on cellular stress responses at the intersection of 1. The Unfolded protein response; 2. Mitochondrial dysfunction; 3. The benefits of mineralocorticoid receptor antagonists. Lastly, perspectives are offered to the readers. Expert opinion: Renal IRI is caused by a sudden and temporary impairment of blood flow to the organ. Defining the underlying cellular cascades involved in IRI will assist us in the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer several advantages compared to targeting downstream inflammatory and fibrosis processes. An improved understanding of the cellular pathophysiological mechanisms leading to kidney injury will hopefully offer improved targeted therapies to prevent and treat the injury in the future.


Subject(s)
Acute Kidney Injury/drug therapy , Kidney Transplantation/adverse effects , Reperfusion Injury/drug therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/physiopathology , Animals , Humans , Mineralocorticoid Receptor Antagonists/pharmacology , Mitochondria/pathology , Molecular Targeted Therapy , Reperfusion Injury/etiology , Reperfusion Injury/physiopathology
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