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Selected AbstractsInhibition of the histamine-induced weal and flare response: a valid surrogate measure for antihistamine clinical efficacy?CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2007P. Devillier Summary Histamine plays a central role in allergic responses. Inhibition of the weal and flare response to histamine is a traditional pharmacodynamic tool to measure the activity of H1 -receptor antagonists. The time course and duration of cutaneous weal and flare inhibition are often used as surrogate measures of clinical efficacy. Pharmacodynamic differences among antihistamines are often interpreted to indicate differences in clinical efficacy. A systematic review of literature from 1980 to 2006 regarding the histamine induced weal and flare was undertaken. Search terms included ,histamine', ,skin test', ,weal', ,flare', and ,antihistamine'; retrieved articles were searched for relevant studies not identified initially. Data from human studies on the inhibition of the weal and flare by second-generation antihistamines were extracted and assessed. A literature search from 1980 to 2006 was undertaken for comparative studies of second-generation antihistamines in the clinical settings of allergic rhinitis (AR) and chronic idiopathic urticaria; data extracted from these studies underwent systematic review. Differences were noted among second-generation antihistamines in terms of their ability to inhibit the histamine-induced weal and flare. Corresponding differences in terms of clinical efficacy in AR and chronic urticaria were not identified following a systematic review. The reasons for the disconnect between pharmacodynamic effects and clinical efficacy may include differences between the route and concentration of histamine, the involvement of mediators other than histamine in the allergic response, and the short time course of pharmacodynamic studies. The histamine-induced weal and flare response is a pharmacodynamic test that should not be used to compare the clinical efficacy of different antihistamines, and is not an adequate alternative to clinical end-point assessments in AR or chronic idiopathic urticaria. [source] Response of the charophyte Nitellopsis obtusa to heavy metals at the cellular, cell membrane, and enzyme levelsENVIRONMENTAL TOXICOLOGY, Issue 3 2002Levonas Manusad, ianas Abstract The responses of the freshwater macroalga Nitellopsis obtusa to heavy metal (HM) salts of Hg, Cd, Co, Cu, Cr, and Ni were assessed at different levels: whole-cell mortality (96-h LC50), in vivo cell membrane (45-min depolarization of resting potential, EC50), and enzyme in plasma membrane preparations (K+, Mg2+ -specific H+ -ATPase inhibition, IC50). To measure ATPase activity, a novel procedure for isolation of plasma membrane,enriched vesicles from charophyte cells was developed. The short-term ATPase inhibition assay (IC50 from 6.0 × 10,7 to 4.6 × 10,4 M) was slightly more sensitive than the cell mortality test (LC50 from 1.1 × 10,6 to 2.6 × 10,3 M), and the electrophysiological test with the end point of 45-min depolarization of resting potential was characterized by less sensitivity for HMs (EC50 from 1.1 × 10,4 to 2.2 × 10,2 M). The variability of IC50 values assessed for HMs in the ATPase assays was close to that of LC50 values in the mortality tests (CVs from 33.5 to 83.5 and from 12.4% to 57.7%, respectively), whereas the EC50 values in the electrophysiological tests were characterized by CVs generally below 30%. All three end points identified two separate HM groups according to their toxicity to N. obtusa: Co, Ni, and Cr comprised a group of less toxic metals, whereas Hg, Cu, and Cd comprised a group of more toxic metals. However, the adverse effects within each group were discriminated differently. For example, the maximum difference between the highest and lowest LC50 for the group of less toxic metals in the long-term mortality test was approximately 60% of the response range, whereas the corresponding difference in IC50 values in the ATPase assay was 30%. In contrast, the LC50 values of the more toxic metals occupied only 10% of the response range, whereas the IC50 values were spread over 70%. Further investigation should be done of the underlying mechanism or mechanisms responsible for the observed differences in the dynamic range of a particular end point of the groups of toxicants of varying strength. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 275,283, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10058 [source] Effect on de novo plaque formation of rinsing with toothpaste slurries and water solutions with a high fluoride concentration (5,000 ppm)EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2009A. Nordström The aim of this study was to evaluate the effect, on de novo plaque formation, of rinsing with toothpaste slurries and water solutions containing a high concentration of fluoride (F). Sixteen subjects rinsed three times per day for 4 d with dentifrice slurries containing 5,000, 1,500, and 500 ppm F, while 12 subjects rinsed with water solutions containing 5,000, 1,500, 500, and 0 ppm F, and 1.5% sodium lauryl sulphate (SLS). Plaque was scored [using the Quigley & Hein index (QHI)] after each 4-d period. Plaque samples for F analysis were collected. Significantly less plaque was scored for the dentifrice slurry containing 5,000 ppm F (buccal and all surfaces) and for 1.5% SLS (buccal surfaces). The differences in plaque scores between dentifrice containing 5,000 and 1,500 ppm F were 19% for all surfaces and 33% for buccal surfaces. The difference between the water solutions containing 1.5% SLS and 1,500 ppm F for buccal surfaces was 23%; the corresponding difference for 5,000 ppm F was 17%. The dentifrice slurry containing 5,000 ppm F accumulated 56% more F in plaque. The combination of high levels of F and SLS in dentifrice reduces de novo plaque formation and increases the accumulation of F in plaque after 4 d. [source] Dark-rearing-induced reduction of GABA and GAD and prevention of the effect by BDNF in the mouse retinaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006Eun-Jin Lee Abstract Gamma-aminobutyric acid (GABA) is an important retinal neurotransmitter. We studied the expression of GABA, glutamate decarboxylase 65 (GAD65) and GAD67 by immunocytochemistry and Western blot, in the retinas of control and dark-reared C57BL/6J black mice. This study asked three questions. First, is visual input necessary for the normal expression of GABA, GAD65 and GAD67? Second, can the retina recover from the effects of dark-rearing if returned to a normal light,dark cycle? Third, does BDNF prevent the influence of dark-rearing on the expression of GABA and GAD? At postnatal day 10 (P10), before eye opening, GABA immunoreactivity was present in the ganglion cell layer (GCL), in the innermost rows of the inner nuclear layer (INL) and throughout the inner plexiform layer (IPL) of control and dark-reared retinas. In P30 control retinas, GABA immunoreactivity showed similar patterns to those at P10. However, in P30 dark-reared retinas, the density of GABA-immunoreactive cells was lower in both the INL and GCL than in control retinas. In addition, visual deprivation retarded GABA immunoreactivity in the IPL. Western blot analysis showed corresponding differences in the levels of GAD65 but not of GAD67 expression between control and dark-rearing conditions. In our study, dark-rearing effects were reversed when the mice were put in normal cyclic light,dark conditions for 2 weeks. Moreover, dark-reared retinas treated with BDNF showed normal expression of both GABA and GAD65. Our data indicate that normal expression of GABA and GAD65 is dependent on visual input. Furthermore, the data suggest that BDNF controls this dependence. [source] General organization of the perinatal and adult accessory olfactory bulb in miceTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 9 2006Ignacio Salazar Abstract The vomeronasal system is currently a topical issue since the dual functional specificity, vomeronasal system-pheromones, has recently been questioned. Irrespective of the tools used to put such specificity in doubt, the diversity of the anatomy of the system itself in the animal kingdom is probably of more importance than has previously been considered. It has to be pointed out that a true vomeronasal system is integrated by the vomeronasal organ, the accessory olfactory bulb, and the so-called vomeronasal amygdala. Therefore, it seems reasonable to establish the corresponding differences between a well-developed vomeronasal system and other areas of the nasal cavity in which putative olfactory receptors, perhaps present in other kinds of mammals, may be able to detect pheromones and to process them. In consequence, a solid pattern for one such system in one particular species needs to be chosen. Here we report on an analysis of the general morphological characteristics of the accessory olfactory bulb in mice, a species commonly used in the study of the vomeronasal system, during growth and in adults. Our results indicate that the critical period for the formation of this structure comprises the stages between the first and the fifth day after birth, when the stratification of the bulb, the peculiarities of each type of cell, and the final building of glomeruli are completed. In addition, our data suggest that the conventional plexiform layers of the main olfactory bulb are not present in the accessory bulb. Anat Rec Part A, 288A:1009,1025, 2006. © 2006 Wiley-Liss, Inc. [source] |