Neurotoxicity of hemoglobin in cortical cell culture.

Hemoglobin (Hb) has been demonstrated to be neurotoxic when injected into the cerebral cortex in vivo. However, associated systemic factors such as ischemia and epileptogenesis have limited investigations of Hb toxicity in the intact central nervous system (CNS). In this study, the neurotoxicity of human Hb was assessed in mixed neuronal and glial neocortical cell cultures derived from fetal mice.

NMDA neurotoxicity in murine cortical cell cultures is not attenuated by hemoglobin or inhibition of nitric oxide synthesis.

The role of nitric oxide in N-methyl-D-aspartate (NMDA) neurotoxicity was investigated in murine cortical cell cultures. Exposure of cultures to 300 microM NMDA for 5 min resulted in death of 50-80% of neurons over the subsequent 24 h. This injury was not attenuated by hemoglobin, the nitric oxide synthase (NOS) inhibitors NG monomethyl-L-arginine (MMA) or N omega-nitro-L-arginine (NA), or L-arginine depletion.

Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin.

Human hemoglobin (Hb) and Hb cross-linked between the alpha subunits with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) were used to treat hemorrhagic shock in water-deprived swine. Water was withheld for 48 h to induce a 10% loss of body mass, and 25 ml/kg of blood were removed in 1 h to produce circulatory shock. Swine were resuscitated with 1) Hb, 2) alpha alpha Hb, 3) human serum albumin, or 4) Ringer lactate.

Compatibility of army face paint and insect repellent formulation.

The compatibility studies of a new controlled-release repellent formulation (NSN 6840-01-284-3982, insect repellent personal application) and a new camouflage face paint (NSN 6850-01-262-0635) indicated that the repellent did not interfere with the use of face paints when repellent was applied first, and the face paints did not reduce the effectiveness of the repellent against mosquitoes.

Lactated Ringer's solution alleviates brain trauma-precipitated lactic acidosis in hemorrhagic shock.

To determine the influence of brain trauma on blood acid-base and lactate-pyruvate responses to hemorrhage, and the effect of lactated Ringer's solution on these responses, 30 anesthetized rats were assigned to four groups: hemorrhage (n = 7), hemorrhage following fluid percussion brain trauma (trauma-hemorrhage group) (n = 7), hemorrhage treated with lactated Ringer's solution (hemorrhage-resuscitation group) (n = 8), and hemorrhage following brain trauma treated with lactated Ringer's solution (trauma-hemorrhage-resuscitation group) (n = 8). The hemorrhage group showed no significant changes in pH, HCO3, and base excess after hemorrhage. Base excess and pH were significantly reduced after the hemorrhage in the trauma-hemorrhage group but were raised after resuscitation in the hemorrhage-resuscitation group.

Acute and subacute toxicity of 7.5% hypertonic saline-6% dextran-70 (HSD) in dogs. 2. Biochemical and behavioral responses.

7.5% Hypertonic saline-6% Dextran-70 (HSD) is currently being evaluated in our laboratory as a resuscitation solution for the treatment of hypovolemia at a dose of 4 ml kg-1 body weight. A few reports of dextran toxicity, particularly of the kidney, have been cited in the literature, so the present study evaluated the acute and subacute toxicity of HSD administered i.

Regeneration of functional hemoglobin from iron(III) hemoglobin by reduction with hydrogen and a heterogeneous catalyst.

Functional hemoglobin was regenerated from partially autoxidized hemoglobin by reduction with molecular hydrogen in the presence of a heterogeneous catalyst consisting of elemental platinum embedded in an electroactive polymer. The visible spectrum of the regenerated hemoglobin was identical to that of native iron(II) hemoglobin. The regenerated hemoglobin displayed highly cooperative oxygen-binding characteristics.

Evaluation of methemoglobin formation during the storage of various hemoglobin solutions.

Many researchers are trying to develop a blood substitute based on chemically modified human hemoglobin. In the process of making such solutions, we were faced with the problem of determining the best storage conditions to minimize oxidation of the solutions between the time of manufacture and use. Samples of stroma-free hemoglobin, purified A0 hemoglobin, and various cross-linked hemoglobins were stored for 8-12 months at +4 degrees C -20 degrees C, and -80 degrees C and were analyzed periodically for formation of methemoglobin (MetHb).

Use of hypertonic saline/dextran versus lactated Ringer's solution as a resuscitation fluid after uncontrolled aortic hemorrhage in anesthetized swine.

Study Objective: We tested the hypothesis that following aortotomy, administration of hypertonic saline/dextran increases hemorrhage and mortality. We also compared hypertonic saline/dextran with the standard therapy of attempting to replace three times the amount of lost blood with lactated Ringer's solution.

Design: In this model of uncontrolled arterial hemorrhage resulting from aortotomy, 24 anesthetized Yorkshire swine underwent splenectomy, stainless steel wire placement in the infrarenal aorta, and instrumentation with Swan-Ganz and carotid artery catheters.

Acute and subacute toxicity of 7.5% hypertonic saline/6% dextran-70 (HSD) in dogs. 1. Serum immunoglobulin and complement responses.

Clinical use of modern dextran solutions has been limited by concerns of anaphylactoid reactions. To assess the short-term antigenic response to 7.5% hypertonic saline in 6% Dextran-70 (HSD), sera were obtained from dogs involved in the acute and subacute toxicology testing of HSD and its individual components, and analyzed for IgG, IgM and C3 complement.

Effect of the repellent deet on the antennal chemoreceptors for oviposition in Aedes aegypti (Diptera: Culicidae).

The insect repellent, N,N-diethyl-m-toluamide (deet), interferes with detection of the host attractant, lactic acid (LA), by LA-excited neurons on the antennae of female Aedes aegypti (L.) mosquitoes. In the current laboratory behavioral experiment, the attraction of gravid female mosquitoes to a source of ethyl propionate, an oviposition attractant, was reduced by a factor of two when deet was present.

Comparison of intraosseous and intravenous delivery of hypertonic saline/dextran in anesthetized, euvolemic pigs.

Study Objectives: With renewed interest in intraosseous (IO) infusion, the present study examined if sternal IO infusion provided vascular entry of 7.5% NaCl/6% dextran-70 (HSD) as efficiently as IV infusion. DESIGN, SETTING, TYPE OF PARTICIPANTS, INTERVENTIONS: Twelve anesthetized pigs were catheterized for measurement of cardiovascular parameters.

Traumatic brain injury attenuates the effectiveness of lactated Ringer's solution resuscitation of hemorrhagic shock in rats.

Traumatic brain injury suppresses spontaneous cardiovascular compensation for hemorrhage, prompting us to examine the possibility that trauma to the brain modifies hemodynamic response to therapy in hemorrhage. Thirty rats that were anesthetized were randomly assigned to four groups--hemorrhagic shock (H), hemorrhagic shock after brain trauma (TH), hemorrhagic shock treated with lactated Ringer's (LR) solution (HR), and hemorrhagic shock after brain trauma treated with LR (THR). After hemorrhage, group TH had significantly lower mean arterial pressure (MAP), cardiac index (CI) and stroke volume index (SVI) than group H.

Pretreatment with NMDA antagonists limits release of excitatory amino acids following traumatic brain injury.

After central nervous system (CNS) trauma, there are marked elevations in the extracellular levels of excitatory amino acids (EAA), which are believed to contribute to delayed tissue damage. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists reduces injury severity after brain or spinal cord trauma, presumably by blocking the postsynaptic NMDA receptor. In the present studies, levels of extracellular amino acids were monitored by microdialysis during, and after, a moderately severe fluid-percussion brain injury to rats.

Meniscal regeneration with copolymeric collagen scaffolds. In vitro and in vivo studies evaluated clinically, histologically, and biochemically.

We sought to create a regeneration template for the meniscal cartilage of the knee to induce complete meniscal regeneration, and to develop the technique for implanting the prosthetic appliance in vivo. We designed a resorbable collagen-based scaffold and conducted in vitro and in vivo studies. In vivo, the scaffold was implanted in the knees of immature swine and mature canines and evaluated clinically, histologically, and biochemically.

Laboratory observations on mating and leklike aggregations in Lutzomyia longipalpis (Diptera: Psychodidae).

The mating behavior of the sand fly, Lutzomyia longipalpis, was studied under laboratory conditions. Male sand flies landed on the bodies of anesthetized mice, where they exhibited leklike displays such as wing fanning, parading, and aggression. Lek behavior was more frequent in older males, and dominance hierarchies were established.

Effects of extraerythrocytic hemoglobin and its components on mononuclear cell procoagulant activity.

Earlier studies performed in rabbits in this laboratory showed that human hemoglobin causes leukocyte infiltration into heart and lung tissues and coagulation abnormalities including thrombosis. Since stimulation of peripheral blood mononuclear cells induces procoagulant activity, we investigated the possibility that isolated peripheral blood mononuclear cells from humans and rabbits were stimulated by hemoglobin to produce a procoagulant activity response. Stroma-free hemoglobin and its purified components were assayed for their stimulatory effect on peripheral blood mononuclear cells.

Oxygen delivery and myocardial function in rabbit hearts perfused with cell-free hemoglobin.

Isolated rabbit hearts were perfused with Krebs-Henseleit buffer that contained 1.5 g/dl hemoglobin Ao [HbAo; PO2 at which half-saturation of hemoglobin occurs = 12 Torr], human hemoglobin cross-linked between alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha-Hb; PO2 at which half-saturation of hemoglobin occurs = 30 Torr), or fatty acid-free bovine serum albumin (BSA). Myocardial performance and oxygen uptake were determined at different aortic PO2's [arterial PO2 (PaO2)] by use of an isovolumic Langendorff preparation.

Effect of dehydration on cardiovascular responses and electrolytes after hypertonic saline/dextran treatment for moderate hemorrhage.

Study Objective: To determine if hypertonic saline/dextran (HSD) is effective in treating hemorrhage in the presence of dehydration.

Design: After surgical preparation, swine were euhydrated or dehydrated for 24 or 48 hours. Animals were bled 25 mL/kg over 60 minutes and treated with HSD.

Resuscitation of intraoperative hypovolemia: a comparison of normal saline and hyperosmotic/hyperoncotic solutions in swine.

Background And Methods: We compared a hypertonic saline-dextran solution (7.5% NaCl/6% dextran-70) with 0.9% NaCl (normal saline) for treatment of intraoperative hypovolemia.

Free radical-mediated lung response to the monofunctional sulfur mustard butyl 2-chloroethyl sulfide after subcutaneous injection.

Vesicant-induced pathogenesis is initiated by rapid alkylation and cross-linking of DNA purine bases causing strand breaks leading subsequently to NAD depletion and cell death. We postulated that vesicants may also be associated with free radical-mediated oxidative stress distal to the site of exposure. To test this postulate in the lung, we injected 3 groups (n = 8) of 5-month-old, male, athymic, nude mice, weighing 30-35 g with a single subcutaneous (s.

Retinal cell and photoreceptor transplantation between adult New Zealand red rabbit retinas.

Adult New Zealand Red (NZR) rabbits were used to determine if the techniques developed in the rat to transplant sheets of photoreceptors could be adapted to larger eyes of the rabbit. Adult donor NZR rabbit retina was cut into small strips, oriented, and drawn up in a small and flat polyethylene tube. By transscleral approach, donor retina was correctly oriented and gently placed into the subretinal space of host retinas that were previously ablated of photoreceptors by intravitreal injection of hemoglobin.

The role of the kidneys in the excretion of chemically modified hemoglobins.

Stroma-free hemoglobin (SFHb) can be chemically modified to prolong the intravascular retention (prevent renal filtration), and to improve oxygen delivering capability for use as a red cell substitute. Hb derivatives radioactively tagged with tritium [3H] or 14C were used to study their metabolic fate following clearance from the circulation. Fully conscious, chronically cannulated rats were treated by exchange transfusion (ET).

Effects of X-linked hemoglobin on in-vitro platelet function.

The in-vitro function of platelets in 1:1 mixtures of fresh whole blood and 10% DBBF alpha-alpha cross-linked hemoglobin in Ringer's acetate buffer was assessed by quantitative aggregation after challenge with common agonists and compared to the function of platelets in similar dilutions of whole blood in saline. Whole blood aggregometry was performed after addition of ADP, collagen, and ristocetin. Aggregation was quantified by measuring the change in impedance as drawn on the chart recording.