Protective effects of diets supplemented with omega-3 polyunsaturated fatty acids and calcium against colorectal tumor formation.

This study is to evaluate the effect of dietary omega-3 polyunsaturated fatty acid (omega-3 PUFA) and/or calcium supplementation on colon tissue of the carcinogenic N-methyl-N-nitrosurea (NMU)-injected rats and to investigate this effect by the assessment of the oxidative stress. The rats were divided into four groups: those fed with a standard diet, with a diet supplemented by omega-3 PUFA, those fed with a diet with calcium, and those fed with a standard diet with the combination of omega-3 PUFA and calcium. Rats were injected with an intrarectal NMU. After 32 weeks, colon tissue specimens and plasma were taken to histopathologically investigate and analyze tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities and erythrocyte MDA levels. The tumor incidences in supplemented-diet groups II and IV were found to be significantly lower when compared with those of the controls (P < 0.05). Superoxide dismutase and glutathione peroxidase antioxidative enzyme activities in colorectal tissue were increased in the study groups when compared with control rats (P < 0.001) and MDA levels were significantly lower than in the controls (P < 0.001) while the levels in group IV were rather decreased than those in group III (P = 0.011). These results suggest that the dietary supplementation of PUFA and/or calcium may be useful in the prevention of colorectal tumor formation.

Comparison of real-time polymerase chain reaction and conventional polymerase chain reaction methods for the rapid identification of Bacillus anthracis.

Bacillus anthracis spores have been shown to be one of the most effective biological weapons. For the rapid detection of B. anthracis spores, several genetic markers, including chromosomal and plasmid-based sequences, were studied with polymerase chain reaction (PCR) methods. In the present study, a method using a primer/probe set based on the pXO1-encoded pag gene for the detection of B. anthracis was tested in addition to culture. Eight pathological samples (four blood-immersed cotton specimens, two spleen tissue specimens, and two blood smears) with confirmed positive results for anthrax were used. All samples were suspended in saline solution and fixed with Gram and Giemsa stains for examination of colony and capsule formation. Amplicons were analyzed on 2% agarose gels with the classic PCR method. For real-time PCR, a fluorescently labeled TaqMan probe was used with a Smartcycler. Positive smear and cotton samples were confirmed with the standard culture and real-time PCR methods, but the same samples were found to be negative with the classic PCR method. A spleen sample known to be positive for B. anthracis was found to be negative with the culture method because of possible contamination with Proteus-type bacteria.

Comparative sporicidal effects of disinfectants after release of a biological agent.

Because of spore formation, Bacillus anthracis is considered the most resistant biological warfare agent known. The present study aimed to assess and compare well-known decontamination routes to inactivate the spores on daily-use environmental tools contaminated previously. To simulate the agent, Bacillus atrophaeus was used. Various environmental samples (such as tile, fabric clothing, wood, protective suit, glass, paper, soil, water, plastic, and metal) that may be contaminated after a biological incident were used as test carriers and inoculated with B. atrophaeus. Sodium hypochlorite, free chlorine, autoclaving, ethylene oxide, hydrogen peroxide, ultraviolet irradiation, and boiling decontaminated the samples. Glutaraldehyde (2%) and free chlorine solution (10,000 mg/L) were also found to be effective in decontaminating the samples and are recommended as alternatives to the use of sodium hypochlorite solution. Soil, tile, paper, and metal were determined to be the most difficult materials to decontaminate. It was concluded that 5% hypochlorite adjusted with acetic acid might also be used for decontamination. Decontamination strategies to reduce contamination of the environment by biological warfare agents need to be applied to mitigate the number of victims, in terms of prominent characteristics like cost-effectiveness and user-friendliness.

Lung toxicity of nitrogen mustard may be mediated by nitric oxide and peroxynitrite in rats.

Nitric oxide (NO) has previously been shown to be responsible for nitrogen mustard (NM)-induced tissue toxicity. Excessive amounts of NO are known to be able to produce peroxynitrite, an important reactive nitrogen compound, by reacting with superoxide. Previous studies reported that NO synthase inhibitors are able to prevent NM toxicity. The aim of this study was to evaluate whether peroxynitrite is also responsible for NM-induced lung tissue damage in rats. Wistar rats were divided into four groups. NM was injected intratracheally and was treated with the selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) (intraperitoneal) or the peroxynitrite scavenger ebselen (intragastric). Control animals were exposed to saline only. NM injection caused both oxidative and nitrosative stress, reflected by dramatically increased levels of the lipid peroxidation end product malondialdehyde (MDA), iNOS activation and urine nitrite-nitrate (NOx) values. Histopathological evaluation demonstrated lung damage with NM exposure. AG blocked iNOS activation and decreased urine NOx levels, and resulted in less histopathological changes in the lung. Although the histopathological outcome was found to be similar to AG, ebselen did not change urinary NOx or lung iNOS levels. Furthermore, ebselen was more able than AG to protect against MDA accumulation. In conclusion, the ability of ebselen to prevent against lung damage without blocking NO synthesis suggests that peroxynitrites may have an important role in the pathogenesis of NM toxicity in addition to NO.

Chemical release at the airport and lessons learned from the medical perspective.

The risk of massive exposure to toxic chemical substances including chemical weapons or industrial chemicals has increased especially during the last century due to the development in industry and chemistry science. This paper aims to describe a real chemical release event and further exposures to personnel working at the Esenboga Airport, Ankara, Turkey, and to give lessons learned. This chemical release was noticed firstly by airport staff giving symptoms including nausea, vomiting, irritation of eyes, itching and rinorrhea. First responders from civil defense unit and a group of health staff including NBC First-aid and Rescue Team gave response to the incident. The increasing number of exposed or suspected cases transferred to hospital were isolated in Emergency Department (ED) following the decontamination at the airport. Due to the characteristic odour and the growing number of the victims, the releasing agent was considered to be likely cyanide or sulfur mustard. Because of the panic amongst the workers, the number of the exposed (real or suspected) people increased up to about 40 and were kept under observation in ED of the hospital. The chromotographic analysis revealed that the agent contained diallyl disulfide, an organo-sulfur compound present at very high concentrations in pure garlic oil. Blood results showed no cyanide and the isolation were terminated. Along with the lessons learned, incident showed that the health facilities should be prepared against such deliberate or accidental mass casualties.

Medical preparedness against chemical and biological incidents for the NATO Summit in Istanbul and lessons learned.

INTRODUCTION: During the 2004 North Atlantic Treaty Organization (NATO) Summit, essential counter-measures, including medical preparedness, were taken to cope with any suspected terrorist case or events including the use of chemical or biological (CB) weapons. The Summit was held in Istanbul, a city that bridges two continents, and involved the participation of many Heads of State, Prime Ministers, and Defense Ministers from 26 NATO countries. METHODS: First responders, including medical Chemical, Biological, Radiological, and Nuclear (CBRN) teams, received special training. Essential equipment, including drugs, antidotes, detectors, etc., was provided and stock-piled. Medical authorities augmented the capacity for identifying and controlling the injuries and any emerging CB incident through the set-up of decontamination units and the procurement of medical devices, antidotes, drugs, and personal protective suits. Additionally, a small part of the recently established NATO-CBRN battalion was welcomed to the Summit and was prepared to perform detection and identification of the agent found in suspicious appearing samples. RESULTS: Although no CB incident was reported during the Summit, extensive experience was gained with respect to medical preparedness against CB terrorism. Sampling, detection, and analysis of toxic materials were taken into account in the medical management. Much laboratory-related work was conducted in the following time period. The laboratory work involved the standardization of sampling and transportation procedures, development of both mobile and reference laboratories, and performing research activities aimed to make the CB analysis more efficient. Although the training of the medical staff was advanced, training should be continuous and supported with educational programs, conferences, meetings, and tabletop and hospital medical exercises throughout the country. CONCLUSION: Multidisciplinary cooperation, training, and preparedness should be provided to basic medical care units and centers as part of the medical planning aimed at perfect detection and surveillance, laboratory analysis, and emergency response.

Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism.

BACKGROUND: The vesicant agents sulfur and nitrogen mustards, which contain chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth, likely changing the utilization of anaerobic glycolysis for energy generation. METHODS: To investigate the effect of nitrogen mustard on cellular energy metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a nitrogen mustard and an analogue of sulfur mustard, were incubated with radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then determined. RESULTS: Glycogen consumption was significantly higher in cells treated with HN2 in a dose-dependent manner compared to untreated cells. Similarly, the amount of end-product lactate was increased, but CO2 was reduced in HN2-treated cells. CONCLUSIONS: Lymphocytes normally use aerobic glycolysis under aerobic conditions, but energy metabolism predominantly involved anaerobic glycolysis after severe intoxication with mustard agent.

Evaluation of protective ointments used against dermal effects of nitrogen mustard, a vesicant warfare agent.

Mustard, a vesicant warfare agent, has cytotoxic, mutagenic, and cytostatic effects via alkylation of DNA and inhibition of DNA replication. Since symptoms appear following a latent period, it can cause some subacute and chronic effects to occur and delay in the treatment. Therefore, the main approach should be the use of protective preparation to reduce the skin toxicity. Thus, this study was conducted in guinea pigs (350-400 g) shaved in areas of 10 x 10 cm. Mechlorethamine HCl (100 mg), a nitrogen mustard derivative, in ethanol was applied by spraying on hairless regions where previously prepared pharmaceutical topical formulations were medicated before. The experimental regions of the animals were kept preserved from environmental factors. Forty-eight hours after the application of the protective ointments and mechlorethamine consecutively, skin-damaging effects were macroscopically evaluated in terms of erythema formation, ulceration, necrosis, and inflammation occurrences. Then, punch biopsy was performed from these damaged sites for histopathological evaluation. Although numerous topical formulations were prepared and tested for protection, according to microscopic examination of the pathologic sections, tissue specimen treated with the ointment containing the mixture of zinc oxide, zinc chloride, dimethylpolysiloxane in a base of petroleum jelly was determined as being the most effective protective against skin injury caused by the vesicant agent.

A proposal for regional chemical and biological defense among the Balkan countries.

In terms of preventing or reducing the mass disaster caused by chemical and biological warfare agents (CBWs), establishing an efficient chemical and biological defense (CBD) system is vital. Balkan countries including Turkey, Greece, Romania, and Bulgaria are located in the "hot region," where some of the neighboring countries have had a CBW production program or do not comply with the international treaties related to the prohibition of CBWs. On the other hand, setting up the CBD is difficult and requires excessive expenditure, which causes a large economical hardship. According to the point of view of Turkish nuclear, biological, and chemical scientists, who are well experienced with CBD, the formation of a CBD system in the Balkan countries would prevent the CBW threat in this region, and in addition, would be able to make a contribution to global security.

A Turkish medical rescue team against nuclear, biological, and chemical weapons.

Medical aid is one of the primary responses given in the deliberate release of weapons of mass destruction for both military and terrorist purposes. From this point of view, a nuclear, biological, and chemical (NBC) Medical Rescue Team was established in the structure of Gulhane Military Medical Academy. The staff in the team is composed of physicians, nurses, and paramedics who are assigned in Medical Intervention Units, Medical Nursing Units, and Decontamination Units, respectively. The main aim of this team is to give a medical response including first aid, airway, breathing, and circulation resuscitation, decontamination, and triage under any NBC attack. For this purpose, the communication and coordination between the team members were standardized. Moreover, the team was equipped with the required protective clothing, masks, antidotes, and other drugs and agents used for victims exposed to NBC weapons. Within this concept, the personnel in the team were trained with respect to first aid and treatment of NBC casualties in both theoretical and practical scenario. All of this background information was used in a practical operation held in Gulhane Military Medical Academy under a chemical attack scenario given.

Morphological and immunohistochemical changes on rat skin exposed to nitrogen mustard.

OBJECTIVE: The aim of this study was to understand the mechanism of nitrogen mustard on skin. METHODS: Nitrogen mustard was applied on ventral skin of 30 rats. Sequential biopsies were taken during the postexposure period. Slides were stained with hematoxylin-eosin and keratin PAN and high molecular weight cytokeratin and keratin 5. RESULTS: The earliest findings are minimal polymorphonuclear leukocytes extravasation and edema. Heavy inflammation with formation of vesicles and bulla were present at 24 hours. At 6 hours, the upper epidermal cells showed weak staining with high molecular weight cytokeratin and keratin PAN. At 24 and 48 hours, only patchy areas of staining with high molecular weight cytokeratin and keratin 5 were present. CONCLUSION: One of the major mechanisms of injury by nitrogen mustard may be the disruption of cytoskeletal filament network.

Evaluations over the medical emergency responding to chemical terrorist attack.

The use of chemical warfare agents intentionally has become a great concern in the arena of the cold war. On the other hand, there has always been a threat on civilian population due to their mass destruction effects, including psychological damage and a great deal of discussion how to respond to it in terms of medical management. It is very important to provide the best lifesaving medical care and triage in a chemical-contaminated area. Mass casualties exposed to chemical agents require immediate medical intervention to save their lives and should be classified in accordance to medical care priorities and available medical sources, including antidotes and sophisticated health facilities. Establishing the decontamination area for chemical casualties where it is located at the suitable place with respect to the wind direction is necessary. To overcome the mass destruction effects of chemical warfare agents following the terrorist attack, we must have the emergency medical response plan involving experienced triage officers and medical care providers to be able to perform medical management in the chemical-contaminated area and health facilities.

The protective and therapeutic effects of zinc chloride and desferrioxamine on skin exposed to nitrogen mustard.

The nitrogen mustard (HN2), which contains chloroethyl groups, is a potent inhibitor of DNA synthesis and cell growth. It also has vesicant properties. Due to these damaging effects of HN2 on the skin, zinc chloride (ZnCl2) and desferrioxamine were used in the form of ointment for treatment and prevention of the histopathological destruction of skin of guinea pigs. According to results of the histopathological study, both ZnCl2 and desferrioxamine had therapeutic and protective effects for HN2-induced skin damage at moderate levels. Taking into consideration the alkylating effect of HN2 on the skin, our results suggest that ZnCl2 and desferrioxamine may be used in the prevention of nuclear damage and for handling the burns caused by the HN2.

Laboratory conditions and safety in a chemical warfare agent analysis and research laboratory.

Toxic chemicals have been used as weapons of war and also as means of terrorist attacks on civilian populations. Research focusing on chemical warfare agents (CWAs) may be associated with an increased risk of exposure to and contamination by these agents. This article summarizes some of the regulations concerning designation and safety in a CWA analysis and research laboratory and medical countermeasures in case of an accidental exposure. The design of such a laboratory, coupled with a set of safety guidelines, provides for the safe conduct of research and studies involving CWAs. Thus, a discussion of decontamination and protection means against CWAs is also presented.