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Biomedical subjects

Michael R Landauer

Publications and source records attributed to Michael R Landauer.

9 recordsLinked to original sources
PubMed2006

Antibacterial activity of the soy isoflavone genistein.

Genistein, a radioprotective soy isoflavone and protein kinase inhibitor, blocks the invasion of pathogenic bacteria in mammalian epithelial cells. The purpose of this study was to evaluate the direct effect of genistein on the survival and growth of the probiotic Lactobacillus reuteri and selected opportunistic bacteria in vitro as a prelude to in vivo use for managing postirradiation sepsis. We evaluated the opportunistic bacterial enteropathogens Escherichia coli, Shigella sonnei, and Staphylococcus aureus as well as Klebsiella pneumoniae and the non-pathogenic organism, Bacillus anthracis (Sterne). The latter two bacteria are found in the environment and may be of concern in irradiated individuals. A standard in vitro test was employed to evaluate the direct effect of genistein on the bacteria. This test involved determining bacterial colony forming unit (CFU) counts at a single concentration of genistein. In the CFU assays, significant reductions in CFUs were found for S. aureus and B. anthracis when cultured in the presence of 100 muM genistein. However, L. reuteri, E. coli, S. sonnei, and K. pneumoniae were not altered by in vitro culturing in the presence of 100 muM genistein. These results demonstrate the in vitro antimicrobial activity of genistein. Furthermore, the use of genistein in combination with probiotics may augment the effectiveness of antimicrobial therapies currently used in the management of infections, including those induced by ionizing irradiation.

Anti-Bacterial Agents↗
PubMed2003

Protection against ionizing radiation by antioxidant nutrients and phytochemicals.

The potential of antioxidants to reduce the cellular damage induced by ionizing radiation has been studied in animal models for more than 50 years. The application of antioxidant radioprotectors to various human exposure situations has not been extensive although it is generally accepted that endogenous antioxidants, such as cellular non-protein thiols and antioxidant enzymes, provide some degree of protection. This review focuses on the radioprotective efficacy of naturally occurring antioxidants, specifically antioxidant nutrients and phytochemicals, and how they might influence various endpoints of radiation damage. Results from animal experiments indicate that antioxidant nutrients, such as vitamin E and selenium compounds, are protective against lethality and other radiation effects but to a lesser degree than most synthetic protectors. Some antioxidant nutrients and phytochemicals have the advantage of low toxicity although they are generally protective when administered at pharmacological doses. Naturally occurring antioxidants also may provide an extended window of protection against low-dose, low-dose-rate irradiation, including therapeutic potential when administered after irradiation. A number of phytochemicals, including caffeine, genistein, and melatonin, have multiple physiological effects, as well as antioxidant activity, which result in radioprotection in vivo. Many antioxidant nutrients and phytochemicals have antimutagenic properties, and their modulation of long-term radiation effects, such as cancer, needs further examination. In addition, further studies are required to determine the potential value of specific antioxidant nutrients and phytochemicals during radiotherapy for cancer.

Animals↗
PubMed2002

Health effects of embedded depleted uranium.

The health effects of embedded fragments of depleted uranium (DU) are being investigated to determine whether current surgical fragment-removal policies are appropriate for this metal. The authors studied rodents implanted with DU pellets as well as cultured human cells exposed to DU compounds. Results indicate that uranium from implanted DU fragments distributes to tissues distant from implantation sites, including bone, kidney, muscle, and liver. Despite levels of uranium in kidney that would be nephrotoxic after acute exposure, no histological or functional kidney toxicity was observed with embedded DU, indicating that the kidney adapts when exposed chronically. Nonetheless, further studies of the long-term health impact are needed. DU is mutagenic and transforms human osteoblastic cells into a tumorigenic phenotype. It alters neurophysiological parameters in rat hippocampus, crosses the placental barrier, and enters fetal tissue. Preliminary data also indicate decreased rodent litter size when animals are bred 6 months or longer after DU implantation.

Animals↗
PubMed2002

Radiation-induced performance decrement.

This article is a brief review of performance decrement expected after low-level radiation doses (0.70 Gy or less) and after higher radiation doses. Examples are presented from both animal and human data. The data indicate that low-level radiation doses in humans are not expected to degrade performance on the battlefield. Doses higher than 1.25 Gy are likely to degrade performance. Transient performance deficits known as early transient incapacitation observed in animals and humans after large, rapidly delivered doses of ionizing radiation are discussed.

Animals↗
PubMed2002

Psychological consequences of military operations in low-level radiation environments.

Military operations have produced neuropsychiatric (NP) casualties throughout history. The same is true for radiation accidents. Although we have not carried out military operations in nuclear environments, related experience suggests that operations performed under low-level radiation conditions could serve to compound the factors that are known to produce NP casualties. Historically, military NP casualty rates have varied widely depending on a complex array of factors, ranging from the actual conditions of the operation and experiences of the soldiers to the perception of the conflict by both the soldiers and the people back home. History has also shown that lack of preparation contributes to NP casualties. The number and severity of NP casualties can be minimized by ensuring that the equipment, training, and leadership are in place to instill in our soldiers the confidence that they can cope with the types of threats that are part of modern-day missions.

Humans↗
PubMed2002

Protection against gamma-irradiation with 5-androstenediol.

We showed previously that treatment of gamma-irradiated female B6D2F1 mice with 5-androstenediol (AED) enhanced survival, stimulated myelopoiesis, and ameliorated radiation-induced decreases in circulating neutrophils and platelets. We have now tested survival in male CD2F1 mice, and we have investigated molecular and functional effects on neutrophils and bone marrow stromal cells and screened for toxicity in female B6D2F1 mice. AED (160 mg/kg, subcutaneously, 24 hours before irradiation) enhanced survival in male CD2F1 mice with a dose-reduction factor of 1.23, similar to the dose-reduction factor of 1.26 found previously for female B6D2F1 mice. Expression of CD11b, a developmental marker, was reduced on circulating neutrophils after either in vivo AED administration or whole-body gamma-irradiation (3 Gy), but neutrophil peroxidase activity was unchanged. Stromal cell progenitors (fibroblastoid colony-forming units) were reduced in marrow 5 days after AED injection in nonirradiated mice. Clinical chemistry, histopathology, and behavioral assays showed no evidence of toxicity. We conclude that AED and related steroids are attractive candidates to explore as countermeasures to high- and low-level ionizing radiation.

Androstenediol↗
PubMed2002

Nuclear, biological, and chemical combined injuries and countermeasures on the battlefield.

The Armed Forces Radiobiological Research Institute (AFRRI) has developed a research program to determine the major health risks from exposure to ionizing radiation in combination with biological and chemical warfare agents and to assess the extent to which exposure to ionizing radiation compromises the effectiveness of protective drugs, vaccines, and other biological and chemical warfare prophylactic and treatment strategies. AFRRI's Defense Technology Objective MD22 supports the development of treatment modalities and studies to assess the mortality rates for combined injuries from exposure to ionizing radiation and Bacillus anthracis, and research to provide data for casualty prediction models that assess the health consequences of combined exposures. In conjunction with the Defense Threat Reduction Agency, our research data are contributing to the development of casualty prediction models that estimate mortality and incapacitation in an environment of radiation exposure plus other weapons of mass destruction. Specifically, the AFFRI research program assesses the effects of ionizing radiation exposure in combination with B. anthracis, Venezuelan equine encephalomyelitis virus, Shigella sonnei, nerve agents, and mustard as well as their associated treatments and vaccines. In addition, the long-term psychological effects of radiation combined with nuclear, biological, and chemical (NBC) injuries are being evaluated. We are also assessing the effectiveness of gamma photons and high-speed neutrons and electrons for neutralizing biological and chemical warfare agents. New protocols based on our NBC bioeffects experiments will enable U.S. armed forces to accomplish military operations in NBC environments while optimizing both survival and military performance. Preserving combatants' health in an NBC environment will improve warfighting operations and mission capabilities.

Biological Warfare↗
PubMedDate not supplied

Genistein treatment protects mice from ionizing radiation injury.

The radioprotective and behavioral effects of an acute administration of the isoflavone genistein (4',5,7-trihydroxyflavone) were investigated in adult CD2F1 male mice. Mice were administered a single subcutaneous (s.c.) dose of genistein either 24 h or 1 h before a lethal dose of gamma radiation (9.5-Gy of cobalt-60 at 0.6 Gy min(-1)). Mice received saline, PEG-400 vehicle or genistein at 3.125, 6.25, 12.5, 25, 50, 100, 200, or 400 mg kg(-1) body weight. For mice treated 24 h before irradiation there was a significant increase in 30-day survival for animals receiving genistein doses of 25 to 400 mg kg(-1) (p<0.001). In contrast, the 30-day survival rates of mice treated with genistein 1 h before irradiation were not significantly different from those of the vehicle control group. Additionally, the acute toxicity of genistein was evaluated in non-irradiated male mice administered a single s.c. injection of saline, vehicle, or genistein at 100, 200 or 400 mg kg(-1). At these genistein doses there were no adverse effects, compared with controls, on locomotor activity, grip strength, motor coordination, body weight, testes weight, or histopathology. These results demonstrate that a single s.c. administration of the flavonoid genistein at non-toxic doses provides protection against acute radiation injury.

Animals↗