Evaluation of the Neuroprotective Efficacy of Newly Developed Oximes (K206, K269) and Currently Available Oximes (Obidoxime,HI‐6) in Cyclosarin‐Poisoned Rats

Abstract: The neuroprotective effects of newly developed oximes (K206, K269) and currently available oximes (obidoxime, HI‐6) in combination with atropine in rats poisoned with cyclosarin were studied. The cyclosarin‐induced neurotoxicity was monitored using a functional observational battery at 24 hr following cyclosarin challenge. The results indicate that a newly developed oxime K206 is able to counteract cyclosarin‐induced neurotoxicity while the neuroprotective potency of another newly developed oxime (K269) is negligible. The neuroprotective efficacy of K206 is markedly higher than commonly used obidoxime; nevertheless, its potency to eliminate cyclosarin‐induced neurotoxicity is slightly lower compared to the oxime HI‐6. Thus, a newly developed oxime K206 seems to be a better oxime for the antidotal treatment of cyclosarin poisonings than obidoxime due to higher neuroprotective potency although the oxime HI‐6 is still the most suitable oxime for the antidotal treatment of acute poisonings with cyclosarin.     

MR imaging of the bowel: pediatric applications

Magnetic resonance enterography with oral contrast administration using fast T2-weighted and fat saturated, contrast-enhanced T1-weighted sequences is the most common technique for bowel evaluation. The main indication for bowel MR imaging in children has been evaluation of inflammatory bowel diseases. A less common application is appendicitis. Other potential applications include evaluation of vascular malformations and transplanted bowel.     

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

Background  

To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ) in subjects with moderate to severe sleep disorders.     

Voiding urosonography with US contrast agent for the diagnosis of vesicoureteric reflux in children: an update

Voiding urosonography (VUS) entails the intravesical administration of US contrast agent (USCA) for the diagnosis of vesicoureteric reflux (VUR). VUS is now recognized as a practical, safe, radiation-free modality with comparable or higher sensitivity than direct radionuclide cystography (DRNC) and voiding cystourethrography (VCUG), respectively. An extensive review of the literature regarding both the procedural aspects and comparative diagnostic values of VUS has been published (Darge Pediatr Radiol 38:40–63, 2008a, b). The aim of this review is to provide an update on various facets of VUS that have taken place since the publication of the above-mentioned two reviews.     

Ultrasound of the bowel in children: how we do it

Advances in US like high-resolution transducers, harmonic imaging and panoramic modality have overcome some of the obstacles for sonography of the small and large bowel that existed in the past. In a number of centers, bowel US is an established routine method both in adults in children. Bowel US has the distinct advantages of being widely available, relatively cheap, free of radiation and easy to perform. In addition, US of the bowel demonstrates both mural and extramural pathological changes. Patients with inflammatory bowel disease have frequent imaging studies due to disease recurrences and need of follow-up after treatment. Thus this group of pediatric patients benefits most from an optimized and standardized bowel US. This review provides a comprehensive step-by-step approach how to perform US of the bowel in children with emphasis on imaging inflammatory bowel changes. It is meant to serve like a recipe and facilitate the routine performance of US of the bowel in children.     

The influence of sarin on various physiological functions in rats following single or repeated low-level inhalation exposure

Long-term effects of low doses of highly toxic organophosphorus agent sarin on various hematological and biochemical markers and physiological functions were studied in rats exposed to sarin by inhalation. The results indicate that low-level sarin-exposed rats show long-term increase in studied markers of stress and decrease in synthesis of DNA de novo without the disturbance of the functions of cholinergic nervous system. Moreover, sarin at low doses is able to induce some neurotoxic effects including an increase in the excitability of central nervous system in rats at 3 mo following inhalation exposure. Relatively long-term spatial discrimination impairments in rats exposed to low-level sarin was demonstrated too. Therefore, nerve agents such as sarin seem to be harmful not only at high, clinically symptomatic doses but also at low doses without acute clinical manifestation of overstimulation of cholinergic nervous system because of long-term manifestation of alteration of neurophysiological and neurobehavioral functions in sarin-exposed rats.     

Should age influence the choice of quantitative bone assessment technique in elderly women? The EPIDOS study

In a prospective cohort of 7,598 women aged 75 and over, we analyzed the effect of age on the ability of femoral neck bone mineral density (BMD) and of ultrasound (BUA and SOS) of the calcaneus to predict hip fracture. Unadjusted regression analysis showed that the risk of hip fracture was increased 1.7 times for one standard deviation increase in age (3.7 years). Overall, for a decrease of one standard deviation in quantitative bone measures, the risk was significantly increased by 2.2 times for BMD (1.9–2.5), 1.8 for BUA (1.6–2.1), and 1.9 for SOS (1.6–2.2). However the average relative risk associated with a decrease in BMD tends to diminish with advancing age, meaning that a smaller part of the risk is explained by BMD in the very elderly. This is confirmed by the areas under the ROC curves (AUC) of BMD that are significantly better before 80 years (0.75 [0.73–0.76]) than after (0.65 [0.63–0.67] in group 80–84 years and 0.65 [0.61–0.68] in group 85). On the other hand, as the absolute risk increases exponentially with age, the number of hip fractures attributable to a low BMD is still important in the very elderly, the risk difference between the lowest and the highest quartile of BMD is 25 hip fractures / 1,000 woman-years in the group 85 compared with 16 in the two other groups. Thus, after 80, quantitative assessment of bone may still be of interest for clinical decisions. Compared with quantitative ultrasound parameters, the ability of BMD to predict hip fracture was significantly superior to that of BUA and SOS only before the age of 80 (AUC of BMD 0.75 [0.73–0.76], BUA 0.67 [0.66–0.69], SOS 0.67 [0.65–0.69]). For patients older than 80, we did not observe significant differences in AUC between DXA and QUS to predict hip fracture.The named authors wrote this article on behalf of the EPIDOS Study Group. Coordinators: G. Bréart and P. Dargent-Molina (epidemiology), P.J. Meunier and A.M. Schott (clinical aspects), D. Hans (DXA and ultrasound quality control), P.D. Delmas (biochemistry). Principal investigators: J.L. Sebert and C. Baudoin (Amiens), A.M. Schott and M.C. Chapuy (Lyon), C. Marcelli and F. Favier (Montpellier), C.J. Menkès, C. Cormier, and E. Hausherr (Paris), and H. Grandjean and C. Ribot (Toulouse).     

A comparison of the potency of newly developed oximes (K005, K027, K033, K048) and currently used oximes (pralidoxime, obidoxime, HI-6) to reactivate sarin-inhibited rat brain acetylcholinesterase by in vitro methods

The potency of newly developed and currently used oximes to reactivate sarin-inhibited acetylcholinesterase was evaluated using in vitro methods. A rat brain homogenate was used as a source of acetylcholinesterase. Significant differences in reactivation potency among all tested oximes were observed. Although the ability of newly developed oximes to reactivate sarin-inhibited acetylcholinesterase does not reach the reactivating potency of the oxime HI-6, the oxime K033 seems to be a more efficacious reactivator of sarin-inhibited acetylcholinesterase than other currently available oximes (pralidoxime, obidoxime) at concentrations (10(-5)-10(-4)M) corresponding to recommended doses in vivo. The results of our study also confirm that the reactivation potency of the tested reactivators depends on many factors, such as (1) the number of pyridinium rings, (2) the number of oxime groups and their position, and (3) the length and the shape of the linkage bridge between pyridinium rings.