More precise localization of nasal tumors associated with chronic exposure of F-344 rats to formaldehyde gas

Considerable interest and research have resulted from the finding that squamous cell carcinomas, polypoid adenomas, and a small number of other nasal neoplasms occurred in F-344 rats following chronic inhalation exposure to formaldehyde. These tumors were reported to originate in the anterior portion of the nasal cavity but their precise location in the nose was not determined. Histologic sections from the nasal passages of these rats have been reexamined and the location of each tumor has been recorded. The majority of squamous cell carcinomas occurred on the anterior portion of the lateral aspect of the nasoturbinate and adjacent lateral wall (57%) or the midventral nasal septum (26%). Polypoid adenomas were confined to a small region of the anterior nasal cavity and were restricted to the free margins of the naso-and maxilloturbinates and lateral wall adjacent to these margins. One neoplasm, considered to be the malignant counterpart of the polypoid adenoma, originated on the dorsal margin of the maxilloturbinate in the same region of the nose. Remaining neoplasms were generally too large or too poorly preserved for assessment of their site of origin. Mechanistic studies directed toward a better understanding of the nasal carcinogenicity of formaldehyde, or other nasal carcinogens, should take into account the anatomic sites of origin of the neoplasms whenever this can be determined.     

Level of work stress and factors associated with bruxism in the military crew of the Peruvian Air Force

BackgroundMilitary life leads to a great personal sacrifice and labor in the aircrew because they are constantly subjected to innumerable activities which have a great work pressure; therefore, the aim of this study was to determine the level of work stress associated with bruxism in the aircrew of the Peruvian Air Force.MethodsThis was a cross-sectional study. A total of 204 crew members of the Peruvian Air Force from the Air Group were surveyed, and the stomatological clinical inspection was carried out. Each crew member was evaluated using the validated International Labor Organization-World Health Organization (ILO-WHO) Work Stress Scale, and clinical records were used to diagnose bruxism using the Smith and Knight wear index.ResultsIt was found that 93.7% (n = 191) of the crew members were men and 6.3% (n = 13) were women; and the percentage of intermediate-level stress was found to be high in the grade of non-commissioned officers, whereas in the officer grade, the level of stress was low. There was also a statistically significant association between the variables military grade, sex, and age group. The sub-officers presented a higher percentage in the category "with bruxism", while in the rank of officers the category of "non-bruxism" was the most prevalent.ConclusionsThis study showed a statistically significant association between the variable bruxism and the level of work stress between the military aviators of the Peruvian Air Force (p<0.001).     

Biomarkers for monitoring transfluthrin exposure: Urinary excretion kinetics of transfluthrin metabolites in rats

The urinary excretion kinetics of a fluorine-containing pyrethroid transfluthrin [(2,3,5,6-tetrafluorophenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate], which is widely used recently as mosquito repellents, was examined in rats to search for urinary metabolites suitable as biomarkers for monitoring transfluthrin exposure of the general population. After a single dose of 26, 64, 160 or 400 mg/kg body weight of transfluthrin had been administered intraperitoneally to male Sprague-Dawley rats, their urine was collected periodically for one week. Three major urinary transfluthrin metabolites were measured: 2,3,5,6-tetrafluorobenzyl alcohol, 2,3,5,6-tetrafluorobenzoic acid and 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid. The kinetics was evaluated by moment analysis of the urinary excretion rate of the metabolites versus time curves.The urinary excretion amounts of these three metabolites were estimated to be proportional to the absorption amounts of transfluthrin over a wide exposure range. Urinary 2,3,5,6-tetrafluorobenzoic acid was considered to be an optimal biomarker for monitoring transfluthrin exposure.     

Differential effects of cadmium administration on peripheral blood granulocytes in rats

Infiltration of circulatory inflammatory cells is a common histopathological finding in target organs following cadmium administration, but there is paucity of data concerning their activity. In this study, the effects of sublethal (1 mg/kg) cadmium on peripheral blood polymorphonuclear (PMN) cells were examined 48 h following administration in rats, when tissue (liver and lung) infiltration of these cells was observed. Cadmium administration resulted in systemic inflammatory cytokine and acute phase response with an increase in circulatory neutrophil numbers and cells that express CD11b molecules. Rise in basic aspects of oxidative activity including intracellular myeloperoxidase (MPO), reactive oxygen (nitroblue tetrazolium/NBT cytochemical assay) and nitrogen (Griess assay) species production was observed in PMNs from cadmium-administered rats. A decrease in levels of mRNA for IL-1β, TNF-α and IL-6 was noted, but production of these cytokines was affected differentially. Described effects of cadmium on PMNs add further to the understanding of inflammatory potential of this environmental contaminant.     

Environmental exposure to organophosphorus nerve agents

Exposure to organophosphorus nerve agents, the most deadly chemical warfare agents, is possible in a variety of situations, such as destruction of chemical warfare agents, terrorist attacks, armed conflicts or accidents in research laboratories and storage facilities. Hundreds of thousands of tons of chemical munitions were disposed of at the sea in the post World War II period, with European, Russian, Japanese and US coasts being the most affected. Sulfur mustard, Lewisite and nerve agents appear to be the most frequently chemical warfare agents disposed of at the sea. Addressing the overall environmental risk, it has been one of the priorities of the world community since that time. Aside from confirming exposure to nerve agents in the alleged use for forensic purposes, the detection and identification of biological markers of exposure are also needed for the diagnosis and treatment of poisoning, in addition to occupational health monitoring for specific profiles of workers. When estimating detrimental effects of acute or potential chronic sub-lethal doses of organophosphorus nerve agents, released accidentally or intentionally into the environment, it is necessary to understand the wide spectra of physical, chemical and toxicological properties of these agents, and predict their ultimate fate in environmental systems.     

A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier for paclitaxel

A novel polyethylene glycol 400 (PEG400) mediated lipid nanoemulsion as drug-delivery carrier for paclitaxel (PTX) was successfully developed. The formulation comprised a PEG400 solution of the drug (25 mg/mL) that would be mixed with commercially 20% lipid emulsion to form PTX-loaded nanoemulsion (1 mg/mL) prior to use. This two-vial formulation of PTX-loaded lipid nanoemulsion (TPLE) could significantly reduce extraction of reticuloendothelial system (RES) organs and increase tumor uptake, and exhibited more potent antitumor efficacy on bearing A2780 or Bcap-37 tumor nude mice compared to conventional PTX-loaded lipid nanoemulsion (CPLE). TPLE did not cause haematolysis and intravenous irritation response yet, and showed the same cytotoxicity against HeLa cells as Taxol®, and its LD₅₀ was 2.7-fold higher than that of Taxol®, suggesting its good safety and druggability. In addition, TPLE displayed distinctly faster release of PTX, a greater proportion of PTX in phospholipids layer and a smaller share in oil phase than CPLE. From the Clinical Editor: This study demonstrates the feasibility and potential advantage of a novel PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in clinical application for the cancer therapy.From the Clinical EditorThis team of investigators convincingly demonstrates the feasibility and potential advantage of a PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in cancer therapy, documenting superior safety and faster release of PTX compared to commercially available formulations.     

Pain and the pharmacogenetics at the fuzzy border between pain physiopathology and pain treatment

Nociceptive pain is time limited and severe nociceptive pain normally responds well to treatment with opioids, On the contrary, neuropatic pain is frequently chronic, and tends to have a less robust response to treatment with opioids. The unsolved problem of insufficient pain treatment at clinical level, including both wanted analgesic effects and unwanted side effects, is a stimulus to expand the knowledge on the physiophatology of pain and on the involved molecular mechanisms. In particular, it is important not only to better understand the molecular mechanisms associated to drugs effects but also to characterize the genetic traits underlying pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms related to drugs. Literature analysis reveals that there are interesting genetic polymorphisms that are associated either to the sensitivity to pain and to PD response to drugs, or to the metabolic and excretion pathways. Pharmacogenetics/pharmacogenomics holds the promise that drugs might in the next future be tailor-made for individuals and adapted to each person's own genetic background. Collected information, allowing to design combined therapies and to dissect analgesic from addictive properties of opioids within a given patient, will also contribute to contrast the persisting opiophobia in medical practice.