Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients’ quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment

Interfacial Structure Dependent Spin Mixing Conductance in Cobalt Thin Films

Enhancement of Gilbert damping in polycrystalline cobalt thin-film multilayers of various thicknesses, overlayered with copper or iridium, was studied in order to understand the role of local interface structure in spin pumping. X-ray diffraction indicates that cobalt films less than 6 nm thick have strong fcc(111) texture while thicker films are dominated by hcp(0001) structure. The intrinsic damping for cobalt thicknesses above 6 nm is weakly dependent on cobalt thickness for both overlayer materials, and below 6 nm the iridium overlayers show higher damping enhancement compared to copper overlayers, as expected due to spin pumping. The interfacial spin mixing conductance is significantly enhanced in structures where both cobalt and iridium have fcc(111) structure in comparison to those where the cobalt layer has subtly different hcp(0001) texture at the interface

Measuring magnetic hysteresis curves with polarized soft X‐ray resonant reflectivity

Calculations and measurements of polarization‐dependent soft X‐ray scattering intensity are presented during a magnetic hysteresis cycle. It is confirmed that the dependence of the intensity on the magnetic moment can be linear, quadratic or a combination of both, depending on the polarization of the incident X‐ray beam and the direction of the magnetic moment. With a linearly polarized beam, the scattered intensity will have a purely quadratic dependence on the magnetic moment when the magnetic moment is parallel to the scattering plane. However, with the magnetic moment perpendicular to the scattering plane, there is also a linear component. This means that, when measuring the hysteresis with linear polarization during a hysteresis cycle, the intensity will be an even function of the applied field when the change in the magnetic moment (and field) is confined within the scattering plane but becomes more complicated when the magnetic moment is out of the scattering plane. Furthermore, with circular polarization, the dependence of the scattered intensity on the moment is a combination of linear and quadratic. With the moment parallel to the scattering plane, the linear component changes with the helicity of the incident beam. Surprisingly, in stark contrast to absorption studies, even when the magnetic moment is perpendicular to the scattering plane there is still a dependence on the moment with a linear component. This linear component is completely independent of the helicity of the beam, meaning that the hysteresis loops will not be inverted with helicity

抗ヒスタミン薬ケトチフェンの連日投与による体内時計位相調節

富山大学・富生命博甲第90号・AHMAD ALSAWAF・2017/03/23Sleep and Biological Rhythms,2016.1,14(1),117-120,doi: 10.1007/s41105-015-0021-yに掲載。富山大学201

Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley rats

BACKGROUND: Catharanthus roseus L (C. roseus) has been used to treat a wide assortment of diseases including diabetes. The objective of our study was to evaluate the antimicrobial and wound healing activity of the flower extract of Catharanthus in rats. METHODS: Wound healing activity was determined in rats, after administration (100 mg kg(-1 )day(-1)) of the ethanol extract of C. roseus flower, using excision, incision and dead space wounds models. The animals were divided into two groups of 6 each in all the models. In the excision model, group 1 animals were topically treated with carboxymethyl cellulose as placebo control and group 2 received topical application of the ethanol extract of C. roseus at a dose of 100 mg/kg body weight/day. In an incision and dead space model group 1 animals were given normal saline and group 2 received the extract orally at a dose of 100 mg kg(-1 )day(-1). Healing was assessed by the rate of wound contraction, period of epithelization, tensile strength (skin breaking strength), granulation tissue weight, and hydoxyproline content. Antimicrobial activity of the flower extract against four microorganisms was also assessed RESULTS: The extract of C. roseus significantly increased the wound breaking strength in the incision wound model compared with controls (P < 0.001). The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly increased in comparison to control wounds (P < 0.001), Wet and dry granulation tissue weights, and hydroxyproline content in a dead space wound model increased significantly (p < 0.05). Pseudomonas aeruginosa and Staphylococcus aureus demonstrated sensitivity to C. roseus CONCLUSION: Increased wound contraction and tensile strength, augmented hydroxyproline content along with antimicrobial activity support the use of C. roseus in the topical management of wound healing

Drug Facilitated Sexual Assault: Detection and Stability of Benzodiazepines in Spiked Drinks Using Gas Chromatography-Mass Spectrometry

Benzodiazepines are detected in a significant number of drug facilitated sexual assaults (DFSA). Whilst blood and urine from the victim are routinely analysed, due to the delay in reporting DFSA cases and the short half lives of most of these drugs in blood and urine, drug detection in such samples is problematic. Consideration of the drinks involved and analysis for drugs may start to address this. Here we have reconstructed the ‘spiking’ of three benzodiazepines (diazepam, flunitrazepam and temazepam) into five drinks, an alcopop (flavoured alcoholic drink), a beer, a white wine, a spirit, and a fruit based non-alcoholic drink (J2O) chosen as representative of those drinks commonly used by women in 16–24 year old age group. Using a validated GC-MS method for the simultaneous detection of these drugs in the drinks we have studied the storage stability of the benzodiazepines under two different storage conditions, uncontrolled room temperature and refrigerator (4°C) over a 25 day period. All drugs could be detected in all beverages over this time period. Diazepam was found to be stable in all of the beverages, except the J2O, under both storage conditions. Flunitrazepam and temazepam were found not to be stable but were detectable (97% loss of temazepam and 39% loss of flunitrazepam from J2O). The recommendations from this study are that there should be a policy change and that drinks thought to be involved in DFSA cases should be collected and analysed wherever possible to support other evidence types

Sigma-1 receptor agonist fluvoxamine for postoperative delirium in older adults: report of three cases

<p>Abstract</p> <p>Background</p> <p>Postoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat this syndrome, these drugs are associated with a variety of adverse events, including sedation, extrapyramidal side effects, and cardiac arrhythmias. Drug treatment for postoperative delirium requires careful consideration of the balance between the effective management of symptoms and potential adverse effects.</p> <p>Methods</p> <p>We report on a Japanese woman (an 86-year-old (open reduction and internal fixation of the right femoral neck fracture), and two Japanese men (an 86-year-old (abdominal aortic aneurysm stent grafting), and a 77-year-old (right upper lobectomy due to lung tumour)) in which the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the postoperative delirium of these patients.</p> <p>Results</p> <p>Delirium Rating Scale scores in these patients dramatically decreased after treatment with fluvoxamine.</p> <p>Conclusions</p> <p>Doctors should consider fluvoxamine as an alternative approach to treating postoperative delirium in older patients in order to avoid the risk of side effects and increased mortality by antipsychotic drugs.</p