Chemical stability of reactive skin decontamination lotion (RSDL®).

Reactive Skin Decontamination Lotion (RSDL®) is used for the decontamination of Chemical Warfare Agents and Toxic Industrial Compounds after dermal exposure. It has to be stockpiled over a long period and is handled in all climatic zones. Therefore stability is an essential matter of concern. In this work we describe a study to the chemical stability of RSDL® as basis for an estimation of shelf life. We analysed RSDL® for the active ingredient 2,3-butandione monoxime (diacetylmonooxime, DAM), the putative degradation product dimethylglyoxime (DMG) and unknown degradation products by means of a reversed phase high pressure liquid chromatography (HPLC). Calculations were done according to the Arrhenius equation. Based on the temperature dependent rate constants, the time span was calculated, until defined threshold values for DAM and DMG subject to specification and valid regulations were exceeded. The calculated data were compared to the ones gathered from stockpiled samples and samples exposed during foreign mission. The decline of DAM followed first order kinetics, while formation of DMG could be described by zero order kinetics. The rate constants were distinctively temperature dependent. Calculated data were in good accordance to the measured ones from stockpile and mission. Based on a specified acceptable DAM-content of 90% and a valid threshold value of 0.1% (w/w) for the degradation product DMG, RSDL® proved to be stable for at least four years if stored at the recommended conditions of 15°C-30°C. If continuously stored at higher temperatures shelf life will decrease markedly. Therefore RSDL® is an object for risk orientated quality monitoring during storage.

Analysis of microarray data from the macaque corpus luteum; the search for common themes in primate luteal regression.

The factors and processes involved in regression of the primate corpus luteum (CL) are complex and not fully understood. Systemic identification of those genes that are differentially expressed utilizing macaque model systems of luteal regression could help clarify some of the important molecular events involved in loss of primate luteal structure and function during luteolysis. In addition, examining gene pathways involved in luteal regression may help elucidate novel approaches for overcoming infertility or designing ovary-based contraceptives. This review provides an overview of the current published microarray experiments evaluating the transcriptome of the macaque CL, and compares and contrasts the data from spontaneous, GnRH antagonist and prostaglandin F2α-induced luteal regression. In addition, further uses of these databases are discussed, as well as limitations of both array technology and the rhesus macaque genome array.

Excessive sleepiness: under-recognized and essential marker for sleep/wake disorder management.

BACKGROUND: Research during the past few decades has provided substantial evidence indicating that excessive sleepiness (ES) and associated sleep/wake disorders can result in significant morbidity and mortality. However, symptomatology (e.g., ES) and the relationships among common morbidities (e.g., cardiovascular disease, metabolic disorders, mood impairment) and sleep/wake disorders remain under-recognized in clinical practice, particularly in primary care. Yet assessment of sleep/wakefulness and associated symptoms can often be easily conducted in the primary care setting, providing valuable information to facilitate the diagnosis and management of sleep/wake disorders. OBJECTIVE: To provide a conceptual and educational framework that helps primary care physicians comprehensively assess, differentially diagnosis, and appropriately manage patients presenting with ES or ES-related sleep/wake disorders. METHODS: Comprised of six sleep specialists and six primary care physicians, the Sleep/Wake Disorders Working Group (SWG) used a modified, two-round Delphi approach to create and harmonize consensus recommendations for the assessment, diagnosis, treatment, and ongoing management of patients with common sleep/wake disorders related to ES. RESULTS: After a review of the relevant literature, the SWG arrived at consensus on a number of clinical recommendations for the assessment and management ES and some of the most commonly associated sleep/wake disorders. Ten consensus statements ­ five each for assessment/diagnosis and treatment/ongoing care ­ were created for ES, insomnia, obstructive sleep apnea, circadian rhythm disorders, restless legs syndrome, and narcolepsy. CONCLUSION: ES and ES-related sleep/wake disorders are commonly encountered in the primary care setting. By providing an educational framework for primary care physicians, the SWG hopes to improve patient outcomes by emphasizing recognition, prompt diagnosis, and appropriate ongoing management of ES and associated sleep/wake disorders.

Judge, jury and executioner: the auto-regulation of luteal function.

Experiments were conducted to further our understanding of the cellular and molecular mechanisms that regulate luteal function in ewes. Inhibition of protein kinase A (PKA) reduced (P < 0.05) secretion of progesterone from both small and large steroidogenic luteal cells. In addition, the relative phosphorylation state of steriodogenic acute regulatory protein (StAR) was more than twice as high (P < 0.05) in large vs small luteal cells. Large steroidogenic luteal cells appear to contain constitutively active PKA and increased concentrations of phosphorylated StAR which play a role in the increased basal rate of secretion of progesterone. To determine if intraluteal secretion of prostaglandin (PG) F2alpha was required for luteolysis, ewes on day 10 of the estrous cycle received intraluteal implants of a biodegradable polymer containing 0, 1 or 10 mg of indomethacin, to prevent intraluteal synthesis of PGF2alpha. On day 18, luteal weights in ewes receiving 1 mg of indomethacin were greater (P < 0.05) than controls and those receiving 10 mg were greater (P < 0.05) than either of the other two groups. Concentrations of progesterone in serum were also increased (P < 0.05) from days 13 to 16 of the estrous cycle in ewes receiving 10 mg of indomethacin. Although not required for decreased production of progesterone at the end of the cycle, intraluteal secretion of PGF2alpha appears to be required for normal luteolysis. To ascertain if oxytocin mediates the indirect effects of PGF2alpha on small luteal cells, the effects of 0, 0.1, 1 or 10 mM oxytocin on intracellular concentrations of calcium were quantified. There was a dose-dependent increase (P < 0.05) in the number of small luteal cells responding to oxytocin. Thus, oxytocin induces increased calcium levels and perhaps apoptotic cell death in small luteal cells. Concentrations of progesterone, similar to those present in corpora lutea (approximately 30 microg/g), prevented the increased intracellular concentrations of calcium (P < 0.05) stimulated by oxytocin in small cells. In large luteal cells the response to progesterone was variable. There was no consistent effect of high quantities of estradiol, testosterone or cortisol in either cell type. It was concluded that normal luteal concentrations of progesterone prevent the oxytocin and perhaps the PGF2alpha-induced increase in the number of small and large luteal cells which respond to these hormones with increased intracellular concentrations of calcium. In summary, large ovine luteal cells produce high basal levels of progesterone, at least in part, due to a constituitively active form of PKA and an enhanced phosphorylation state of StAR. During luteolysis PGF2alpha of uterine origin reduces the secretion of progesterone from the corpus luteum, but intraluteal production of PGF2alpha is required for normal luteolysis. Binding of PGF2alpha to receptors on large luteal cells stimulates the secretion of oxytocin which appears to activate PKC and may also inhibit steroidogenesis in small luteal cells. PGF2alpha also activates COX-2 in large luteal cells which leads to secretion of PGF2alpha. Once intraluteal concentrations of progesterone have decreased, oxytocin binding to its receptors on small luteal cells also results in increased levels of intracellular calcium and presumably apoptosis. Increased secretion of PGF2alpha from large luteal cells activates calcium channels which likely results in apoptotic death of this cell type.

Biomonitoring of human exposure to carcinogenic nitroaromatic compounds: a pilot study on DNA adduct formation by 1,6-dinitropyrene in rats.

DNA adduct formation by 1,6-dinitropyrene (DNP) was examined in various rat tissues. Intraperitoneal administration of 0.2, 1.0 or 5.0 mg DNP/kg b.w. caused the formation of one major and, at the higher doses, two minor DNA adducts. The highest level of about 300 adducts/10(9) nucleotides was found in urinary bladder DNA. 5-10-fold lower adduct levels were found in the DNA of white blood cells (WBC), liver, lung and small intestinal mucosa. DNA adduct levels in the bladder were highest in Sprague-Dawley males followed by Sprague-Dawley females and Wistar males. Administration by gavage was less effective than intraperitoneal injection. Intratracheal instillation of microcrystalline DNA suspensions did not lead to any detectable adduct formation. The results indicate that WBC DNA may not be a reliable DNA source for biomonitoring human exposure to nitroarenes and that nitroarene-DNA adducts may only be detectable at high levels of exposure.

A flashing-light method for recording centric relation.

A flashing-light system has been described which provides a simple method for ensuring equalized pressure in recording the relationship of the mandible to the maxillae. The wires that protrude from the mouth do not appear to create any discomfort or distraction during the procedures. This method tends to be more comfortable than extraoral or intraoral tracing techniques. The method may create patient fear because an electrical device is used in the oral cavity. In addition, if the metal surfaces (pins and cups) are not fully coated with wax, there may be contact with adjacent soft tissue, which creates an electric sensation.