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[en] Engagement of glucocorticoid-induced TNFR-related protein (GITR) enables the costimulation of both CD25-CD4+ effector (Teff) and CD25+CD4+ regulatory (Treg) cells; however, the effects of GITR-costimulation on Treg function remain controversial. In this study, we examined the effects of GITR ligand (GITRL) binding on the respective functions of CD4+ T cells. GITRL-P815 transfectants efficiently augmented anti-CD3-induced proliferation and cytokine production by Teff cells. Proliferation and IL-10 production in Treg were also enhanced by GITRL transfectants when exogenous IL-2 and stronger CD3 stimulation was provided. Concomitant GITRL-costimulation of Teff and Treg converted the anergic state of Treg into a proliferating state, maintaining and augmenting their function. Thus, GITRL-costimulation augments both effector and regulatory functions of CD4+ T cells. Our results suggest that highly activated and increased ratios of Treg reverse the immune-enhancing effects of GITRL-costimulation in Teff, which may be problematic for therapeutic applications using strong GITR agonists
[en] Corticosteroids have been often found to be added to a dietary supplement for the purpose of illegally improving the effect of their products. Thus, it is imperative to develop or improve a method that enables one to rapidly and reliably analyze corticosteroids in health or dietary supplements, for the safety management purpose. In the present study, results from liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) experiments for the selected 35 corticosteroid compounds are presented, which can be useful for the qualitative screening of corticosteroids in health or dietary supplements. Specifically, retention times, accurate mass data of the protonated steroids, m/z values of major fragment ions are given for the 35 corticosteroids. Further, fragmentation pathways for the selected steroids are also suggested. Based on the suggested fragmentation pathways, it was shown that an unknown steroid compound can be readily identified using the knowledge of a group of unique and specific common skeletal fragments. The high selectivity and sensitivity of the LC-Q-TOF-MS/MS results combined with the knowledge of the fragmentation pathways can offer a new opportunity for rapid and accurate screening of corticosteroids, thus preventing health-related incidents involving adulterated products and clamping down on illegally circulated health products.
[en] Various species of rodents are distinguished by their radiosensitivity (increasing): bank vole < Wistar rat < wild mouse < CC57Br mouse < golden hamster < BALB mouse < guinea pig. There is a positive correlation between radiosensitivity of these species and catecholamines content in the adrenals, urea and blood; and negative correlation between radiosensitivity and adrenaline and noradrenaline concentrations in liver and spleen cells. Presumable causes of this correlation, and the possibility of application of the index under study for predicting the organism radiosensitivity and forecasting the outcome of radiation damage are discussed
[en] Objective: To assess awareness (knowledge, attitude and practices) regarding protective measures for adverse events following long term use of corticosteroids Study design: Cross sectional Study duration and settings: Study was conducted at department of Medicine, Federal Government Service Hospital, Islamabad. Study duration was 6 months (January 2018 to June 2018) Material and methods: A sample size of 150 patients was calculated using WHO calculator. Non probability consecutive sampling was used. Ethical approval and consent forms were taken patients were assessed for awareness through asking structured questions on knowledge, attitude and practices regarding protective measures. Data was analyzed with SPSS version 23. Chi-square test was applied p value . 0.05 was considered significant. Results: Total 150 patients were included in study. Mean age of patients was 39 years}16.2 SD. There were 80(53 percent) male and 70(47 percent) female. Awareness was reported in 28(19 percent) patients while 122(81 percent) were not aware of protective measures. Awareness is significantly associated with occupation, attitude and practices (p<0.05) while insignificantly associated with age, gender and knowledge (p>0.05). Conclusion: Significantly lower awareness regarding protective measures against adverse events of long term corticosteroid usage was found. However, awareness can be improved through conduction of workshops/conferences related to corticosteroid use, adverse event and prevention of complications. (author)
[en] The development of the eye in vertebrates is dependent upon glucocorticoid signalling, however, specific components of the eye are sensitive to synthetic glucocorticoids. The presence of synthetic glucocorticoids within the aquatic environment may therefore have important consequences for fish, which are heavily reliant upon vision for mediating several key behaviours. The potential ethological impact of synthetic glucocorticoid oculotoxicity however has yet to be studied. Physiological and behavioural responses which are dependent upon vision were selected to investigate the possible toxicity of prednisolone, a commonly occurring synthetic glucocorticoid within the environment, during early life stages of zebrafish. Although exposure to prednisolone did not alter the morphology of the external eye, aggregation of melanin within the skin in response to increasing light levels was impeded and embryos exposed to prednisolone (10 μg/l) maintained a darkened phenotype. Exposure to prednisolone also increased the preference of embryos for a dark environment within a light dark box test in a concentration dependent manner. However the ability of embryos to detect motion appeared unaffected by prednisolone. Therefore, while significant effects were detected in several processes mediated by vision, changes occurred in a manner which suggest that vision was in itself unaffected by prednisolone. Neurological and endocrinological changes during early ontogeny are considered as likely candidates for future investigation. - Highlights: • The oculotoxicity of prednisolone was assessed during zebrafish embryogenesis. • Exposure to 10 μg/l resulted in a darkened phenotype during light adaptation. • Preference for a dark environment was differentially altered by prednisolone. • The detection of motion appeared unaffected by all concentrations of prednisolone. • Effects are hypothesised to be mediated via non-visually controlled pathways. - Exposure to prednisolone alters physiological and behavioural responses to visual stimuli during zebrafish embryogenesis via proposed non-ocular mechanisms.
[en] Introduction: The acromio-clavicular (AC) joint is very susceptible to degenerative processes that result in pain and functional impairment. One common modality of treatment has been local infiltration of the joint space. Although this procedure has produced notable positive results, needle misplacement occurs frequently. The aim of this investigation is to evaluate the effects of an intra articular infiltration by comparing precise needle placement into the joint space using high-resolution-ultrasound with the conventional palpation technique. Methods: This prospective and randomized pilot study analysed 20 patients who were assigned either to the 'ultrasound' or the 'palpation' group. Clinical examinations were performed before treatment and at 1 h, 1 week and 3 weeks after a single infiltration of local anaesthetic and corticoid carried out by one specialist. Results: In both groups significant improvement in pain and function was obtained up to one-week post injection. Function remained significantly improved until the last follow-up and did not differ between the two groups. The agent was administered in all patients into the joint space in the ultrasound group. Conclusion: Ultrasound guided infiltration of the AC joint is an easily achieved procedure without any complications. However, clinical follow-up did not differ between free-hand and ultrasound-guided AC joint space infiltration.
[en] The purpose of this work was to demonstrate the presence of α-adrenoceptors in a crude membrane preparation made from rabbit bladder base and urethra. This was achieved by radioligand binding studies, using 3H-dihydro-α-ergocryptine (3H-DHE) as the radioligand. The specific binding, i.e. the binding that could be inhibited by 10-5 M phentolamine, was saturable with 73 fmol 3H-DHE bound per mg membrane protein. Binding was at steady state after 60 min., and reversible. Rate constants for association and dissocation were 3x107 M-1 min.-1, and 2x10-2 min.-1, respectively. A number of compounds were tested for their abilities to complete with 3H-DHE for the binding sites. The relative affinity of some adrenoceptor agonists was (-)-adrenaline>(-)-noradrenaline much larger than (+-)-isoprenaline. Steroselectivity was shown, since (-)-noradrenaline had 42 times higher affinity than (+)-noradrenaline. Adrenoceptor antagonists inhibited 3H-DHE binding in the following order of potency: DHE>phentolamine much larger than (+-)-propranolol. The dissociation constant, Ksub(D), for DHE to the binding sites was estimated in three different ways. The constants were derived from saturation, competition, and kinetic studies, and gave Ksub(D) values of 1.1,1.4 and 0.7 nM, respectively. The results suggest that α-adrenoceptors were labelled by 3H-DHE in the tissue homogenates. (author)
[en] The high-pressure liquid chromatography (= HPLC) was used in simultaneous determinations of a few pg epinephrine and norepinephrine. This separation procedure improves the efficiency when compared with the conventional thin-layer chromatographic methods (TLC) and allows routine assays in plasma. (orig.)
[de]Die Hochdruckfluessigkeitschromatographie (HPLC) wurde zur radioenzymatischen Simultanbestimmung weniger pg Adrenalin und Noradrenalin eingesetzt. Dieses Drennverfahren steigert die Leistungsfaehigkeit im Vergleich zu den bisher ueblichen duennschichtchromatographischen (= TLC) Methoden. Es ermoeglicht routinemaessige Handhabung der Plasmaanalysen. (orig.)
[en] Background: Radio-contrast media (CM)-related adverse reactions are important clinical problems that may cause fatal anaphylaxis. Accordingly, it has been common practice to premedicate patients who have had previous reactions to CM with corticosteroids, antihistamines, and H2 blockers to prevent hypersensitive reactions. However, the effectiveness of premedication has not been properly demonstrated, especially in cases related to non-ionic CM. In this study, we evaluated the effectiveness of premedication at preventing of non-ionic CM immediate-type hypersensitivity reactions. Methods: A total of 30 patients who had been pretreated with corticosteroid and H1 antihistamines and/or H2 blockers in a 3-year period were enrolled. The results of premedication were evaluated in terms of clinical characteristics and the features of breakthrough reactions. Results: Hypersensitivity reactions were not prevented in 5 of the 30 patients who had experienced prior CM reactions (overall recurrence rate after premedication 16.7%; 4/17 patients with mild previous reactions, and 1/13 patients with severe previous reactions). The recurrence rate after premedication was significantly higher in patients with mild previous reactions than in those with severe reactions (23.5% vs. 7.7%; p < 0.001). The breakthrough reactions were similar to the prior reactions in terms of severity and clinical manifestations. Conclusion: Premedication with corticosteroid and H1 antihistamines and/or H2 blockers effectively prevent non-ionic CM-related adverse events in most patients who have had severe previous reactions to CM. However, physicians should be aware of the possibility of premedication failing and of breakthrough reactions, even in cases in which the previous reactions were mild.