Anabolic-androgenic steroid administration causes hypertrophy of immobilized and nonimmobilized skeletal muscle in a sedentary rabbit model.

Although the use of anabolic agents in athletics has generated extensive publicity and controversy, the potential therapeutic benefits of these drugs have not been fully investigated. This randomized, blinded experimental study investigated whether short-term administration of an anabolic-androgenic steroid can limit immobilization-induced muscle atrophy in a rabbit model. We casted one hindlimb each in 48 New Zealand White rabbits and randomly assigned the rabbits to two groups.

U.S. Army soldiers' perceptions of arthropod pests and their effects on military missions.

A survey was conducted to determine the effects of biting and stinging arthropods on military personnel, operations, and training. Nearly 70% of respondents reported experiencing problems attributable to arthropods. Arthropods obstructed movement and field position, prevented concealment and cover, disrupted maneuvers, and caused panic.

Ultrastructure of excitotoxic neuronal death in murine cortical culture.

Ischemic and traumatic brain injury are likely to involve neuronal injury triggered by glutamate receptor overactivation. Although excitotoxic neuronal injury has been widely studied in the setting of primary culture, the extent to which these in vitro injury paradigms resemble in vivo ischemic injury morphologically has not previously been well studied. We studied glutamate receptor mediated neuronal death by transmission electron microscopy and light microscopy.

Autogenous replacement of the meniscus cartilage: analysis of results and mechanisms of failure.

Autogenous replantation of meniscal cartilage (resection of 80% of the meniscus cartilage followed by immediate replantation) was performed in 14 dogs as a control arm of a meniscal replacement study. The purpose was to assess the ability of the excised tissue to heal to the intact rim and function as a meniscus cartilage. This procedure is an idealized model of allografting meniscus cartilage in that the tissue is fresh, autogenous, and perfectly sized.

Efficacy of a fibrin hemostatic bandage in controlling hemorrhage from experimental arterial injuries.

Objective: To determine if a pressure dressing containing fibrinogen and thrombin could provide more effective control of arterial hemorrhage than a pressure dressing alone in an animal model of arterial injury.

Design: Randomized acute (nonsurvival) experiment in swine.

Setting: Federal biomedical research institute.

Dose response effects of hypertonic saline and dextran on cardiovascular responses and plasma volume expansion in sheep.

Despite the established efficacy of 7.5% NaCl/6% dextran-70 in the treatment of hypovolemia, the optimal formulation of a hyperosmotic/hyperoncotic small volume resuscitation solution has yet to be defined. The present study investigates the cardiovascular effects of hypertonic saline ranging from 3.

Overt vitamin B-6 deficiency affects rat pancreatic digestive enzyme and glutathione reductase activities.

Previous reports suggest that vitamin B-6 deficiency contributes to pancreatic insufficiency. However, the susceptibility of pancreatic function to marginal vitamin B-6 intake has not been defined. The present study examines digestive enzyme activity and steady-state mRNA levels, as well as antioxidant enzyme status from rats fed different vitamin B-6 diets.

Review of modified hemoglobin research at Letterman: attempts to delineate the toxicity of cell-free tetrameric hemoglobin.

In the final two years, June 1991 to June 1993, of the Letterman Army Institute of Research, a variety of cell, tissue, organ, and animal systems were used to explore the toxicities of model hemoglobin (Hb) solutions produced in the sterile Hb production facility. Human mononuclear cells release TNF alpha and Il-8 when exposed to chromatographically purified human Hb (HbA0). Mixed cultures of fetal mouse neurons and glial cells exhibit neuronal death with exposure to HbA0 in a dose and time dependent manner while the glial cells are not injured.

Hemoglobin stimulates mononuclear leukocytes to release interleukin-8 and tumor necrosis factor alpha.

Incubation of human mononuclear leukocytes (MNL) with human stroma-free hemolysate (SFH), purified adult hemoglobin Ao (HbAo), and oxidized HbAo (METHb) caused MNL to release compounds into the supernate that mediated neutrophil (polymorphonuclear leukocytes, PMN) chemotaxis and PMN adherence to human umbilical vein endothelial cells (HUVEC). Chemotaxis and PMN adherence to HUVEC were reduced significantly when supernates were preincubated with neutralizing antibodies to interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha), respectively, suggesting that IL-8 and TNF-alpha played significant roles in mediating these activities. Greatest chemotactic activity was observed in supernates of MNL treated with HbAo; while greatest PMN/endothelial cell (EC) adherence activity was observed in supernates of MNL treated with METHb.

Diaspirin cross-linked hemoglobin: tissue distribution and long-term excretion after exchange transfusion.

This report describes the tissue distribution and long-term (14-day) excretion of hemoglobin cross-linked between the alpha-chains (alpha alpha Hb) with carbon 14-labeled bis(3,5-dibromosalicyl)fumarate. Fully conscious, chronically cannulated rats (n = 40) were treated with a 50% isovolemic exchange transfusion (ET) with solutions of 14C-labeled alpha alpha Hb (8.0 gm/dl) and were then monitored for as long as 14 days.

Studies on the inheritance of repellent tolerances in Aedes aegypti.

Two laboratory strains and 6 inbred strains of Aedes aegypti were tested against deet, ethyl hexanediol, dimethyl phthalate, and Indalone. Reciprocal crosses and backcrosses of 2 inbred strains were tested against deet only. Results obtained were compatible with a quantitative genetic model in which the effects of the factors involved were multiplicative.

A review of the efficacy and safety of 7.5% NaCl/6% dextran 70 in experimental animals and in humans.

Recent years have seen a renewed interest in the use of hypertonic-hyperoncotic solutions as plasma volume expanders for the treatment of hemorrhagic hypotension. In particular, a number of studies in experimental animals have addressed the efficacy and safety of small-volume infusions of 7.5% NaCl/6% dextran 70 (HSD).

Trauma and military applications of blood substitutes.

Purpose: To review potential clinical uses of erythrocyte substitutes in treating military battlefield casualties, with specific emphasis on combat injury rates and wounding patterns, resuscitation doctrine and logistic requirements.

Methods: Review of published medical literature and of unclassified documents from the U.S.

Denatured hemoglobin increases human blood mononuclear cell procoagulant effect.

Purpose: To study the effects of the common contaminants of hemoglobin solutions, red cell stroma, bacterial endotoxin, and denatured hemoglobin on the causes of the thrombotic lesions which have been reported in animal experiments after hemoglobin administration.

Protocol: Human blood mononuclear cells were isolated on Ficoll-Hypaque gradients and incubated with hemoglobin from the LAIR production facility, red cell stroma, bacterial endotoxin (E. coli, Wittaker Bioproducts), and hemoglobin denatured by boiling.

Vasoconstrictor effects in isolated rabbit heart perfused with bis(3,5-dibromosalicyl)fumarate cross-linked hemoglobin (alpha alpha Hb).

To study the mechanism by which cell-free hemoglobin preparations may alter coronary vascular reactivity, we investigated the effect of human hemoglobin cross-linked between alpha chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) on the vasomotor response to acetylcholine (ACh) in isolated perfused rabbit hearts. Dose-response curves were generated by monitoring the increase in coronary pressure during serial addition of 0.2-10 microM ACh before, during and after 20 min infusion of three test solutions: a) 0.

A comparison of rates of heme exchange: site-specifically cross-linked versus polymerized human hemoglobins.

The stability of the heme-globin interaction of chemically modified human hemoglobin (Hb) was tested by measuring rates of heme loss from methemoglobin. Heme transfer from methemoglobin to human serum albumin was measured by rapid-scanning spectrophotometry, and the resulting absorption matrices were analyzed by singular value decomposition. Unmodified human HbA0, hemoglobin cross-linked between beta subunits with either 2-nor-2-formylpyridoxal 5'-phosphate or 3,5-(dibromosalicyl)fumarate (DBBF), hemoglobin cross-linked between alpha subunits with DBBF, and pyridoxalated hemoglobin polymerized with either glycolaldehyde or glutaraldehyde were tested.

Assessment of hemoglobin-dependent neurotoxicity: alpha-alpha crosslinked hemoglobin.

Adult human hemoglobin A0 (HbA0) has been shown to be neurotoxic, and we wish to report on similar studies conducted using a modified hemoglobin, which has been crosslinked between the alpha subunits (alpha-alpha Hb). Cortical cell cultures were prepared from fetal Swiss-Webster mice at 15-16 days gestation. Mature cultures (days in vitro, 12-16) were exposed to alpha-alpha Hb in a defined medium for 24-48 hours at 37 degrees C.

Increased vascular resistance with hemoglobin-based oxygen carriers.

Purpose: To compare the effects of resuscitation with hemoglobin-based oxygen-carriers and conventional resuscitation fluids on hemodynamics, oxygen transport, and oxygen consumption in an animal model of the use of these fluids in the treatment of hemorrhagic shock.

Protocol: Twenty-eight immature swine were surgically prepared, allowed to recover five days, water deprived for 48 hours, hemorrhaged of 25 ml/kg over one hour, resuscitated promptly with 1) Ringer's lactate, 75 ml/kg, 2) 7% albumin in Ringer's acetate, 25 ml/kg, 3) 9% unmodified hemoglobin in Ringer's acetate, 25 ml/kg, or 4) 9% alpha alpha-crosslinked hemoglobin in Ringer's acetate, 25 ml/kg, and observed with three hours of hemodynamic and oxygen transport measurements.

Results: Systemic and pulmonary vascular resistance were increased in hemoglobin-treated animals to more than twice the levels seen in crystalloid- or colloid-treated controls.

Resuscitation from hypovolemia in swine with intraosseous infusion of a saturated salt-dextran solution.

Prehospital fluid resuscitation of traumatic injury is limited by difficulty in delivering large volumes of fluid in the field and time delays associated with gaining vascular access. We addressed these limitations in 14 anesthetized swine by evaluating a highly efficient volume expander, a near-saturated salt-dextran solution (SSD) administered through a new device, which gains vascular access via intraosseous (IO) infusion into the sternal bone marrow. After a steady-state baseline was achieved, all animals were hemorrhaged to 45 mm Hg for one hour.

In vivo viability studies of two additive solutions in the postthaw preservation of red cells held for 3 weeks at 4 degrees C.

An optimized additive solution was developed for the postthaw preservation of red cells that contained adenine, glucose, disodium phosphate, and citrate buffer. This solution, called AS-17, was compared to AS-3 solution in a clinical trial using 40 subjects (20 in each arm). Fresh-frozen red cells were thawed and deglycerolized after 1 to 18 months and subjected to a second period of storage in either solution for up to 3 weeks at refrigerator temperatures.

Acute changes in systemic blood pressure and urine output of conscious rats following exchange transfusion with diaspirin-crosslinked hemoglobin solution.

This report describes acute changes in systemic blood pressure and urine output observed after a 50-percent isovolemic exchange transfusion (ET) with diaspirin-crosslinked hemoglobin (alpha alpha Hb). Stroma-free Hb was crosslinked between the alpha chains by using a 14C-labeled diaspirin, bis(3,5-dibromosalicyl)fumarate. Forty conscious, chronically cannulated rats underwent ET with 14C-labeled alpha alpha Hb solution (8.

Mutagenic potential of nitroguanidine and nitrosoguanidine in the Drosophila melanogaster sex-linked recessive lethal assay.

Nitroguanidine (NG) and its degradation product nitrosoguanidine (NSG) were evaluated for their mutagenic potential by using Drosophila melanogaster sex-linked recessive lethal (SLRL) assay. Following 72 h of feeding exposure, NG and NSG at concentrations of 4-8 micrograms ml-1 and 15-20 mg ml-1, respectively, were not mutagenic in the test system. The frequencies of mutations for NG and the negative control were 0.

Further evaluation of the effects of 7.5% sodium chloride/6% Dextran-70 (HSD) administration on coagulation and platelet aggregation in hemorrhaged and euvolemic swine.

In previous studies, we determined that incubation of high concentrations of the 7.5% saline (HS) component of HSD with human blood, in vitro, significantly prolonged prothrombin time (PT), and reduced platelet aggregation. Considering the rapid plasma volume expansion following HSD infusion, the present study tested the hypothesis that any HS-induced effects on coagulation would have no clinical significance when HSD was infused for the treatment of hemorrhagic hypotension.

Resuscitation of hypovolemia in pigs using near saturated sodium chloride solution in dextran.

A 7.5% sodium chloride/6% Dextran solution (HSD) is effective for restoration of cardiovascular function after hemorrhagic shock. In the present experiments, we tested the usefulness and side effects of a 25% NaCl/24% Dextran solution (SSD), compared to HSD and 0.

Bombesin-induced changes in expression of pancreatic enzymes in young and old rats.

Bombesin is known to induce pancreatic growth. In aged animals, reduced responsiveness of tissues of the gastrointestinal tract to a number of hormones/peptides, including bombesin, has been demonstrated, yet the effects of chronic bombesin administration on the aging pancreas is poorly understood. In the present study, groups of 4- and 20- to 22-month-old male Fischer 344 rats were infused by osmotic minipump with saline (control) or bombesin (300 ng/kg/h) for 14 days.