Selective red blood cell depletion by apheresis in sheep causes severe normovolemic anemia.

Background: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4-6 g dL using apheresis in sheep.

Oxygen carriers affect kidney immunogenicity during machine perfusion.

Normothermic machine perfusion provides a powerful tool to improve donor kidney preservation and a route for the delivery of pharmacological or gene therapeutic interventions prior to transplantation. However, perfusion at normothermic temperatures requires adequate tissue oxygenation to meet the physiological metabolic demand. For this purpose, the addition of appropriate oxygen carriers (OCs) to the perfusion solution is essential to ensure a sufficient oxygen supply and reduce the risk for tissue injury due to hypoxia.

Cross-linked Triblock Peptide Capsules as Potential Oxygen Carriers.

Perfluorodecalin (PFD)-filled capsules have been studied for over 15 years as artificial oxygen carriers. However, none of these capsules combines good biocompatibility, good mechanical stability and dispersion stability. Here we propose to use synthetic triblock peptides containing a central block of cysteine units as a cross-linking shell material for capsules with both good biocompatibility and stability.

Triglyceride-filled albumin-based nanocapsules: A promising new system to avoid discarding poorly water-soluble drug candidates.

Even though current drug discovery provides a variety of potential drug candidates, many of those substances are difficult to formulate due to their poor water-solubility. To overcome this obstacle a technological formulation is crucial. Albumin-based nanocarriers are a possible intravenous delivery system which is already approved and commercially available.

Introduction of machine perfusion of donor hearts in a single center in Germany.

Introduction: Organ shortage, subsequent use of extended donor criteria organs and high-risk recipients needing redo-surgery are increasing the complexity of heart transplantation. Donor organ machine perfusion (MP) is an emerging technology allowing reduction of ischemia time as well as standardized evaluation of the organ. The aim of this study was to review the introduction of MP and analyze the results of heart transplantation after MP in our center.

Deciphering the Emulsification Process to Create an Albumin-Perfluorocarbon-(o/w) Nanoemulsion with High Shelf Life and Bioresistivity.

This work aimed at the development of a stable albumin-perfluorocarbon (o/w) emulsion as an artificial oxygen carrier suitable for clinical application. So far, albumin-perfluorocarbon-(o/w) emulsions have been successfully applied in preclinical trials. Cross-linking a variety of different physical and chemical methods for the characterization of an albumin-perfluorocarbon (PFC)-(o/w) emulsion was necessary to gain a deep understanding of its specific emulsification processes during high-pressure homogenization.

Artificial oxygen carriers in organ preservation: Dose dependency in a rat model of ex-vivo normothermic kidney perfusion.

Introduction: Organ preservation through ex-vivo normothermic perfusion (EVNP) with albumin-derived perfluorocarbon-based artificial oxygen carriers (A-AOCs) consisting of albumin-derived perfluorodecalin-filled nanocapsules prior to transplantation would be a promising approach to avoid hypoxic tissue injury during organ storage.

Methods: The kidneys of 16 rats underwent EVNP for 2 h with plasma-like solution (5% bovine serum albumin, Ringer-Saline, inulin) with or without A-AOCs in different volume fractions (0%, 2%, 4%, or 8%). Cell death was determined using TdT-mediated dUTP-biotin nick end labeling (TUNEL).

Development of a Lyophilization Process for Long-Term Storage of Albumin-Based Perfluorodecalin-Filled Artificial Oxygen Carriers.

Every day, thousands of patients receive erythrocyte concentrates (ECs). They are indispensable for modern medicine, despite their limited resource. Artificial oxygen carriers (AOCs) represent a promising approach to reduce the need for ECs.

Perfluorocarbon-based oxygen carriers: from physics to physiology.

Developing biocompatible, synthetic oxygen carriers is a consistently challenging task that researchers have been pursuing for decades. Perfluorocarbons (PFC) are fascinating compounds with a huge capacity to dissolve gases, where the respiratory gases are of special interest for current investigations. Although largely chemically and biologically inert, pure PFCs are not suitable for injection into the vascular system.

Albumin-derived perfluorocarbon-based artificial oxygen carriers can avoid hypoxic tissue damage in massive hemodilution.

Artificial blood for clinical use is not yet available therefore, we previously developed artificial oxygen carriers (capsules) and showed their functionality in vitro and biocompatibility in vivo. Herein, we assessed the functionality of the capsules in vivo in a normovolemic hemodilution rat-model. We stepwise exchanged the blood of male Wistar-rats with medium either in the presence of capsules (treatment) or in their absence (control).

Prevention of Decompression Sickness by Novel Artificial Oxygen Carriers.

Unlabelled: For three decades, studies have demonstrated the therapeutic efficacy of perfluorocarbon (PFC) in reducing the onset of decompression trauma. However, none of these emulsion-based preparations are accepted for therapeutic use in the western world, mainly because of severe side effects and a long organ retention time. A new development to guarantee a stable dispersion without these disadvantages is the encapsulation of PFC in nanocapsules with an albumin shell.

Synthesis and characterisation of aqueous haemoglobin-based microcapsules coated by genipin-cross-linked albumin.

Bovine serum albumin (BSA)-coated haemoglobin (Hb)-microcapsules prepared by co-precipitation of Hb and MnCO may present an alternative type of artificial blood substitute. Prepared microcapsules were analysed by Scanning electron microscopy (SEM) and Respirometry, cytotoxicity was evaluated by addition of microcapsules to murine fibroblast-derived cell line L929 (American Type Culture Collection, NCTC clone 929 of strain L). The capsules come along with a mean diameter of approximately 0.

When the Brain Yearns for Oxygen.

Nearly 30 years ago hypoxia-inducible factor (HIF) was described as a protein complex bound to regulatory DNA sequences termed hypoxia response elements because HIF binding induced transcription of the erythropoietin gene under hypoxia. However, it soon became clear that HIF is part of a ubiquitous cellular oxygen sensing system, which ensures finely tuned control of HIF abundance and activity in dependence of the cellular oxygen tension. For their discoveries of how cells sense and adapt to oxygen availability Gregg L.

Perfluorocarbons for the treatment of decompression illness: how to bridge the gap between theory and practice.

Decompression illness (DCI) is a complex clinical syndrome caused by supersaturation of respiratory gases in blood and tissues after abrupt reduction in ambient pressure. The resulting formation of gas bubbles combined with pulmonary barotrauma leads to venous and arterial gas embolism. Severity of DCI depends on the degree of direct tissue damage caused by growing bubbles or indirect cell injury by impaired oxygen transport, coagulopathy, endothelial dysfunction, and subsequent inflammatory processes.

Artificial Oxygen Carriers-Past, Present, and Future-a Review of the Most Innovative and Clinically Relevant Concepts.

Blood transfusions are a daily practice in hospitals. Since these products are limited in availability and have various, harmful side effects, researchers have pursued the goal to develop artificial blood components for about 40 years. Development of oxygen therapeutics and stem cells are more recent goals.

Albumin-derived perfluorocarbon-based artificial oxygen carriers: A physico-chemical characterization and first in vivo evaluation of biocompatibility.

Until today, artificial oxygen carriers have not been reached satisfactory quality for routine clinical treatments. To bridge this gap, we designed albumin-derived perfluorocarbon-based nanoparticles as novel artificial oxygen carriers and evaluated their physico-chemical and pharmacological performance. Our albumin-derived perfluorocarbon-based nanoparticles (capsules), composed of an albumin shell and a perfluorodecalin core, were synthesized using ultrasonics.

Perfluorodecalin-Filled Poly(n-butyl-cyanoacrylate) Nanocapsules as Potential Artificial Oxygen Carriers: Preclinical Safety and Biocompatibility.

With regard to the development of artificial blood substitutes, perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules are already discussed for the use as artificial oxygen carriers. The aim of the present study was to thoroughly investigate the preclinical safety and biocompatibility of the perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules prepared by interfacial polymerization. Nanocapsules were assessed for physical and microbial stability.

Safety of poly (ethylene glycol)-coated perfluorodecalin-filled poly (lactide-co-glycolide) microcapsules following intravenous administration of high amounts in rats.

The host response against foreign materials designates the biocompatibility of intravenously administered microcapsules and thus, widely affects their potential for subsequent clinical use as artificial oxygen/drug carriers. Therefore, body distribution and systemic parameters, as well as markers of inflammation and indicators of organ damage were carefully evaluated after administration of short-chained poly (vinyl alcohol, (PVA)) solution or poly (ethylene glycol (PEG))-shielded perfluorodecalin-filled poly (d,l-lactide-co-glycolide, PFD-filled PLGA) microcapsules into Wistar rats. Whereas PVA infusion was well tolerated, all animals survived the selected dose of 1247 mg microcapsules/kg body weight but showed marked toxicity (increased enzyme activities, rising pro-inflammatory cytokines and complement factors) and developed a mild metabolic acidosis.

Artificial oxygen carriers based on perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules.

Poly(n-butyl-cyanoacrylate)-nanocapsules filled by perfluorodecalin (PFD) are proposed as potential oxygen carriers for blood substitute. The capsule dispersion is prepared via interfacial polymerisation from a PFD emulsion in water which in turn is generated by spontaneous phase separation. The resulting dispersion is capable of carrying approximately 10% of its own volume of gaseous oxygen, which is approximately half of the capacity of human blood.

Acid-base and electrolyte status during normovolemic hemodilution with succinylated gelatin or HES-containing volume replacement solutions in rats.

Background: In the past, several studies have compared different colloidal replacement solutions, whereby the focus was usually on the respective colloid. We therefore systematically studied the influence of the carrier solution's composition of five approved colloidal volume replacement solutions (Gelafundin, Gelafusal, Geloplasma, Voluven and Volulyte) on acid-base as well as electrolyte status during and following acute severe normovolemic hemodilution. The solutions differed in the colloid used (succinylated gelatin vs.

Long-circulating poly(ethylene glycol)-coated poly(lactid-co-glycolid) microcapsules as potential carriers for intravenously administered drugs.

The intrinsic advantages of microcapsules with regard to nanocapsules as intravenous drug carrier systems are still not fully exploited. Especially, in clinical situations where a long-term drug release within the vascular system is desired, if large amounts of drug have to be administered or if capillary leakage occurs, long-circulating microparticles may display a superior alternative to nanoparticles. Here, microcapsules were synthesised and parameters such as in vitro tendency of agglomeration, protein adsorption and in vivo performance were investigated.

Nerve growth factor and brain-derived neurotrophic factor but not granulocyte colony-stimulating factor, nimodipine and dizocilpine, require ATP for neuroprotective activity after oxygen-glucose deprivation of primary neurons.

In previous work, we have demonstrated by radiolabeling, mass spectrometry and site-directed mutagenesis that nerve growth factor (NGF) as well as brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) are capable of ATP-binding and that this binding appears to be essential for their neuroprotective activity. In this study, we attempted to shed some light on the question whether ATP is a general prerequisite for neuroprotection. Therefore, we used the non-ATP-binding granulocyte colony-stimulating factor (GCSF), the calcium antagonist nimodipine and the NMDA antagonist dizocilpine to find out whether they need ATP for neuroprotection comparable to NGF and BDNF.

ATP-NGF-complex, but not NGF, is the neuroprotective ligand.

We have shown previously that nerve growth factor (NGF) requires only low nanomolar ATP concentrations in the cell culture medium to protect cortical rat neurons (CRN) from cellular damage induced by staurosporine (STS). We have also demonstrated before that NGF and other growth factors form stable non-covalent complexes with ATP. Here we demonstrated that 8N(1)ATP-NGF, but not NGF, protected CRN against damage.