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Biomedical subjects

J A Knight

Publications and source records attributed to J A Knight.

134 records · Page 8Linked to original sources

Lipid peroxidation in platelet concentrates: effects of leukocyte removal by filtration.

Increased lipid peroxidation (LP) occurs in the presence of various transition, metal ions, including copper and iron, as well as various heme moieties. In addition, irradiation significantly increases LP. The degree of LP, as determined by the liquid chromatographic measurement of plasma malondialdehyde (MDA), can be significantly reduced by the addition of various metal chelating agents and other antioxidants to both stored red blood cells and platelet concentrates. They are also effective in reducing the degree of LP following irradiation. In the current study, leukocytes were effectively removed by filtration from platelet concentrates prepared by standard methods (mean +/- SD before filtration, 460 +/- 286 per microL vs 0.3 +/- 0.2 per microL after filtration). The removal of the white blood cells significantly reduced the plasma MDA levels in the leukocyte-free platelet concentrates compared with concentrates containing leukocytes after storage for 4, 7, and 11 days (P < 0.001; P < 0.02; P < 0.05, respectively). In addition, plasma potassium levels were also significantly reduced in the leukocyte-free platelet concentrates (P < 0.001). Our results suggest that the early removal of leukocytes from platelet concentrates may be helpful in prolonging platelet viability and longevity.

Blood Platelets↗

Lipid peroxidation in platelet concentrates: effects of irradiation and metal chelators.

Increased red cell lipid peroxidation (LP) occurs in the presence of ionized iron, as well as with various heme moieties and other transition metal ions. In stored erythrocytes, the degree of LP, as determined by plasma malondialdehyde measurements, can be significantly reduced by the addition of various metal chelating agents. The current study also showed significant reductions in LP in platelet concentrates, compared with controls, following the addition of the metal chelators ethylenediaminetetraacetic acid (EDTA; P < 0.001), diethylenetriaminepentaacetic acid (DTPA; P < 0.001), and deferoxamine mesylate (DM; P < 0.01). In addition, compared with non-irradiated controls, increased LP was noted following the irradiation of platelet concentrates (P < 0.05). These results suggest that the addition of various metal binding chelators may be effective in increasing the viability and longevity of stored platelet concentrates.

Blood Platelets↗

Lipid peroxidation compared in stored whole blood with various nutrient-anticoagulant solutions.

Since the introduction of acid-citrate-dextrose (ACD) in 1947 to anticoagulate and preserve whole blood for transfusion, various improved formulas, such as citrate-phosphate-dextrose-adenine (CPDA-1), have been successfully introduced, extending the current acceptable blood storage time to 35 days. Additional nutrient-anticoagulant solutions, including CPDA-2, CPDA-3, AS-1, and AS-5, among others, have more recently been studied with comparable results. In this study, lipid peroxidation (LP) was compared, as determined by the measurement of plasma malondialdehyde (MDA) by liquid chromatography, in stored blood preserved with various nutrient solutions with blood treated with CPDA-1. Although minor but inconsistent differences were noted with most of these solutions compared with CPDA-1, AS-1 gave consistently lower MDA levels (P < 0.01). Further improvements in red cell storage and viability may require approaches other than nutrient formula variations, such as the addition of metal chelating agents or other selected antioxidants to the nutrient-anticoagulant solutions, donor supplementation with vitamin free radical scavengers, or other as yet undetermined conditions.

Adenine↗

The effect of vitamins C and E on lipid peroxidation in stored erythrocytes.

Vitamins C and E are both naturally occurring free radical scavengers; as such, their presence assists various other mechanisms in decreasing numerous disruptive free radical processes from taking place, including lipid peroxidation (LP). Vitamin C, being water soluble, is an excellent antioxidant in plasma, while lipid soluble vitamin E is effective in cell membranes. In this communication, our study is reported of the effects of oral vitamin C and E supplementation in human volunteers on stored red cell LP. It was found that supplementation with these vitamins for 10 days prior to blood donation significantly decreased LP in stored red cells in both irradiated and non-irradiated samples in comparison to pre-vitamin red cell LP. Plasma potassium levels were also decreased on days 7 and 14 after storage at 4 degrees C, but not after four additional days (day 18) at 37 degrees C. In agreement with prior studies, in which various metal chelators and other antioxidants were shown to decrease LP, this study further supports the suggestion that, in addition to adding various important nutrient solutions to donor blood, as well as the possible in vitro addition of various metal chelators and other antioxidants, the oral supplementation with vitamin free radical scavengers may further improve the longevity and viability of stored red cells.

Ascorbic Acid↗

The effect of desferrioxamine on stored erythrocytes: lipid peroxidation, deformability, and morphology.

Acid-citrate-dextrose (ACD) was introduced in 1947 as a nutrient-anticoagulant solution to preserve stored whole blood. A decade later, the introduction of citrate-phosphate-dextrose (CPD) resulted in the successful preservation of whole blood for 21 days. In 1978, added adenine and increased glucose concentration (CPDA-1) increased storage to 35 days. More recently, other solutions such as AS-1, further increased the acceptable storage time of packed cells, but cost and inconvenience have limited their use. Several recent studies have investigated the possibility of increasing the shelf-life of whole blood by the addition of various antioxidants. In the current study a comparison was made of the effects of the metal chelator desferrioxamine on several parameters of stored red cells. Thus, measurement was made of plasma malondialdehyde levels, a measure of lipid peroxidation, red cell filtration times, a measure of red cell deformability, and red cell morphology by electron microscopy. Our results showed that adding desferrioxamine significantly decreased levels of plasma malondialdehyde (MDA) and slowed the loss of erythrocyte deformability. Although red cell morphology suggested that the treated cells maintained their normal appearance longer than untreated cells, the differences were not statistically significant. These results suggest that the addition of desferrioxamine to CPDA-1 anticoagulated blood might be effective in prolonging the viability of stored erythrocytes.

Antioxidants↗

Reactive oxygen species and the neurodegenerative disorders.

The major neurodegenerative disorders include Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis. Although their etiology and pathogenesis are unknown, numerous recent studies suggest that oxygen-derived free radicals play an important role. Furthermore, these reactive oxygen species are probably important in brain ischemia and reperfusion, Down's syndrome, and the mitochondrial encephalopathies. In this review, evidence for oxygen-derived free radicals in the pathogenesis of these disorders is discussed.

Aging↗

Advances in the analysis of cerebrospinal fluid.

The laboratory examination of cerebrospinal fluid (CSF) continues to play an important role in the clinical diagnosis and treatment of various disorders of the central nervous system (CNS). The major conditions currently include, as they have in the past, infectious diseases, neoplastic processes, multiple sclerosis, other demyelinating disorders, and intracerebral hemorrhage. Recent publications suggest a variety of new laboratory tests that may be useful in the evaluation of patients with both primary and metastatic malignancies, Alzheimer's disease, Creutzfeld-Jacob disease, global ischemia, various psychiatric disorders, CSF otorrhea and rhinorrhea, and in the differential diagnosis of cortical vs lacunar stroke, among others. Examples of these recent developments and their possible clinical usefulness are discussed.

Amines↗

Free radicals: their history and current status in aging and disease.

Oxygen toxicity was first described in laboratory animals in 1878 and was further established in 1899. The first experiment regarding a free radical reaction was reported in 1894. However, it was not until the late 1940s to early 1950s that retrolental fibroplasia in premature newborns was recognized as being due to oxygen toxicity and not until the late 1960s to early 1970s that newborn bronchopulmonary dysplasia and adult respiratory distress syndrome were appreciated by the medical community. Moreover, the presence of free radicals in biological systems was not generally considered likely until the discovery of superoxide dismutase in 1969, although in the 1950s the basis of oxygen toxicity and X-irradiation was proposed to be by a common free radical mechanism and the radical theory of aging was hypothesized. Oxyradicals are now widely accepted as being very important, not only in the aging process but also in numerous human diseases/disorders where they have either a primary or secondary role. Currently, there are extensive global basic research efforts to define more clearly the role of free radicals and oxidative stress in these conditions. Continuing clinical research will lead to more reliable treatment and preventive measures for many of them. In this review, a short history is presented and the current status of free radicals and oxidative stress in aging and various diseases is discussed.

Aging↗