Artificial oxygen carrier with pharmacologic actions of adenosine-5'-triphosphate, adenosine, and reduced glutathione formulated to treat an array of medical conditions.

Effective artificial oxygen carriers may offer a solution to tackling current transfusion medicine challenges such as blood shortages, red blood cell storage lesions, and transmission of emerging pathogens. These products, could provide additional therapeutic benefits besides oxygen delivery for an array of medical conditions. To meet these needs, we developed a hemoglobin (Hb)-based oxygen carrier, HemoTech, which utilizes the concept of pharmacologic cross-linking.

Adenosine-5'-triphosphate-adenosine-glutathione cross-linked hemoglobin as erythropoiesis-stimulating agent.

An effective hemoglobin (Hb)-based blood substitute that acts as a physiological oxygen carrier and volume expander ought to stimulate erythropoiesis. A speedy replacement of blood loss with endogenous red blood cells should be an essential feature of any blood substitute product because of its relatively short circulatory retention time and high autoxidation rate. Erythropoiesis is a complex process controlled by oxygen and redox-regulated transcription factors and their target genes that can be affected by Hb physicochemical properties.

ATP-adenosine-glutathione cross-linked hemoglobin as clinically useful oxygen carrier.

To attenuate hemoglobin's (Hb) intrinsic toxicity, Texas Tech University scientists developed a novel concept of "pharmacologic cross-linking" to formulate an effective oxygen carrier, HemoTech, which consists of purified bovine Hb cross-linked intramolecularly with ATP and intermolecularly with adenosine, and conjugated with reduced glutathione (GSH). In this composition, while ATP prevents Hb dimerization, adenosine permits the formation of homogeneous polymers. ATP also serves as a regulator of blood vessel tone via activation of the P2Y receptor, whereas adenosine counteracts the vasoconstrictive and pro-inflammatory properties of Hb via stimulation of adenosine A2 and A3 receptors.

Effect of pioglitazone on platelet aggregation in a healthy cohort.

Background: Peroxisome proliferator-activated receptor (PPAR) agonists can favorably influence atheroma proliferation, lipoprotein metabolism and macrovascular complications. Pioglitazone, one of the thiazolidinedione compounds, is a PPAR ligand activator and a clinically important PPAR agonist. There is controversy in the literature about its potential antiplatelet effects.

Gender differences in platelet aggregation in healthy individuals.

This study evaluated gender variability in platelet aggregation in response to common agonists. Platelet aggregation was measured in 36 healthy men and women free of any antiplatelet medication, aged 22-36 years, of Caucasian (White not of Hispanic origin), Hispanic, and African-American not of Hispanic origin. In this ex-vivo study, we investigated platelet aggregation in response to adenosine-5'-diphosphate (ADP), epinephrine (EPI), arachidonic acid (AA) and collagen (COL), using a platelet ionized calcium aggregometer (Chrono-Log Co.

Control of oxidative reactions of hemoglobin in the design of blood substitutes: role of the ascorbate-glutathione antioxidant system.

Uncontrolled oxidative reactions of hemoglobin (Hb) are still the main unresolved problem for Hb-based blood substitute developers. Spontaneous oxidation of acellular ferrous Hb into a nonfunctional ferric Hb generates superoxide anion. Hydrogen peroxide, formed after superoxide anion dismutation, may react with ferrous/ferric Hb to produce toxic ferryl Hb, fluorescent heme degradation products, and/or protein-based free radicals.

Intrinsic toxicity of hemoglobin: how to counteract it.

The development of safe and effective blood substitutes is of great importance in both civilian and military medicine. The currently tested hemoglobin (Hb)-based oxygen carriers, however, have toxicity and efficacy problems. A number of unwanted effects have been observed in human trials, creating doubts about their clinical usefulness.

Evaluation of angiotensin converting enzyme (ACE)-like activity of acellular hemoglobin.

Despite the tremendous progress in research on hemoglobin (Hb) cellular and molecular responses, the current understanding of Hb's overall intrinsic toxicity is still limited. The complete mechanism of Hb-induced vasoconstriction has not yet been established, particularly the involvement of the renin-angiotensin system (RAS). Some studies emphasized that Hb may augment the vascular responsiveness to angiotensin (Ang)-II.

Role of free hemoglobin in 8-iso prostaglandin F2-alpha synthesis in chronic renal failure and its impact on CD163-Hb scavenger receptor and on coronary artery endothelium.

Free hemoglobin (Hb) during autoxidation increases 8-iso-prostaglandin-F2-alpha (8-isoprostane) formation in vitro. Because 8-isoprostane and plasma Hb are elevated in chronic renal failure (CRF), we evaluated the role of Hb in this isoprostane synthesis in vivo. By monitoring correlations between Hb, haptoglobin (Hp), CD163-Hb-scavenger receptor, and 8-isoprostane that is known to induce CD163 shedding, we examined whether 8-isoprostane blocks Hb catabolism in CRF.