Results 1 - 10 of 2374
Results 1 - 10 of 2374. Search took: 0.029 seconds
|Sort by: date | relevance|
[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] 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] As part of their studies into the feasibility of using radiation in the pharmaceutical industry for the purpose of sterilization or lowering the level of microbiological contamination, the author have conducted experiments with 50 kinds of pharmacological products including 40 types of raw materials and 10 types of preparations (mainly ointments) and model formulae. The samples studied may be grouped as follows: effective substances (glucocorticoids, antibiotics, etcor); biochemical products; auxiliary materials used in ointments, tablets, etc.; ointments, primarily those used in ophthalmology. Physical, chemical, and, in some cases, biochemical factors were considered in relation to radiation tolerance. Most of the samples were also subjected to detailed microbiological study. It is concluded that radiosterilization is a promising method as regards the products investigated. (auth.)
[en] Objective: To evaluate the efficacy of intravenous dexamethasone for preventing postoperative nausea and vomiting in women undergoing gynecological laparoscopic surgery. Design: Double blind trial. Place and duration of Study: December 2001 to June 2002 at Hayatabad Medical Complex, Peshawar. Patients and Methods: A 100 admitted female patients of ASA-1-II scheduled for diagnostic gynecological laparoscopic surgery were included in this study. Patients with severe systemic or endocrine disease who had predisposing factors for delayed gastric emptying, such as diabetes, chronic choleystills neuromuscular disorders were excluded. In addition patients who suffered from postoperative nausea and vomiting (PONV) or had received and antiemetic agent or narcotic medications within last 24 hours were also excluded. Patients were divided into two equal groups, patients in one group were given dexamethasone while saline was injected to patients in the second group. Nausea and vomiting were assessed immediately after operation, at 1 hour interval for 4 hours in the recovery and from 410 hours in the Ward. Result was compared in two groups by chi-square test. Results: During patient's stay in the Post anesthesia Care Unit (4 hours postoperatively) 26% patients in the dexamethasone group in comparison with 54% of patients in the saline group reported PONV (P<0.01). Sixteen percent of patients in the dexamethasone group, in comparison with 28% of patients in the saline group needed rescue antiemtic (P 0.05), postoperative nausea vomiting (P<0.01). During the postoperative observation period of 10 hours, 42% of the patients in the dexamethasone group in comparison with 82% of patients in the saline group reported postoperative nausea and vomiting (P<0.01). Conclusion: Dexamethasone significantly reduced the incidence of postoperative nausea and vomiting in women undergoing laparoscopic surgery. Furthermore, it is freely available, is less costly and has few side-effects. So, it should be more frequently used as prophylactic antiemetic in women undergoing gynecological laparoscopic surgery. (author)
[en] Glucocorticoid hormones are involved in regulation of cell processes and coordinate physiological response to diverse signals. These hormones, through interaction with specific intracellular receptors, coordinate components of physiological repertoires by activating the expression of gene networks. Thus hormone-receptor complexes may function as key constituent in regulation of specific cell functions as well as in provoking differentiation in already determined cells. Analysis of steroid receptors are important for understanding of molecular details of transcriptional control as well as providing the insight as to how an individual transcriptional factor such as glucocorticoid receptor, contributes to cell identity and function. The purpose of this review is to establish the general molecular mechanism of glucocorticoid action and mechanism associated hormone-receptor complexes with the control of differential patterns (i.e. "positive" and "negative") of gene expression. One of the examples of two signal pathways regulating opposite gene expression are NF-kB and GR-mediated signal pathways. These pathways have important and opposite roles in the immune function. NF-kB is transcription factor which induces the expression of many genes that participate in immune and inflamatory response, while GR is transcription factor that serves as antiinflammatory agent and immune suppressor. Their interactions within the cell, although not yet completely understood, appear to be an important, possibly even the primary mechanism of immune homeostasis. It has not been established that glucocorticoid sensitivity can be caused by mechanisms other than changes of GR number and properties, although recent studies have indicated that receptor isoforms and transcriptional factors may modulate glucocorticoid responsiveness by interacting with receptor protein or directly at the site of DNA binding. The aim of this review is also to describe the role of glucocorticoid receptors in mechanism of glucocorticoid action on cell functions, including immune responses, as well as to present emerging issues on clinical aspects of molecular mechanisms of glucocorticoid action.
[en] It is reported that 10-7M cortisol has a significant suppressive effect on radiation-induced transformation in vitro in C3H10T 1/2 cells. Previously reported data showed a significant enhancing effect for similar experiments performed with cortisone. Thus, these two structurally similar glucocorticoid hormones have opposite effects on transformation induced by ionizing radiation. (author)
[en] We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.
[en] The monitoring of salivary cortisol as a key biomarker of an individual’s stress response has been increasingly focused on. This paper describes the development of a novel cortisol immuno-assay method based on an indirect competitive method using a commercially available surface plasmon resonance instrument. The surface of an Au chip was modified with PEG6-COOH aromatic dialkanethiol self-assembled monolayers and hydrocortisone 3-(O-carboxymethyl) oxime (hydrocortisone 3-CMO) as a cortisol analog. A detection limit of 38 ppt range with a measurement range of 10 ppt–100 ppb was accomplished without the incubation of a mixing solution consisting of standard cortisol and an anti-cortisol antibody, and the time for quantification of cortisol concentration was 8 min from the sample injection. We experimentally compared our immuno-assay with a commercialized salivary cortisol enzyme-linked immunosorbent assay (ELISA) kit using human saliva samples. It was found that the results obtained by the cortisol immuno-assay had a good correlation with those obtained by ELISA assay (R = 0.96). Our findings indicate the potential utility of the cortisol immuno-assay for measurements of human salivary cortisol levels.
[en] We have studied the interactions of glucocorticoid hormones with radiation in the induction of transformation in vitro in C3AH10T1/2 cells. We have observed that cortisone has its primary enhancing effect on radiation transformation when present after the radiation exposure during the ''expression period'', or the time after carcinogen exposure during which promoting agents have been shown to enhance radiation transformation in vitro, and that two different glucocorticoid hormones, dexamethasone and cortisone, have a suppressive effect on the 12-O-tetradecanoylphorbol-13-acetate (TPA) enhancement of radiation transformation in vitro
[en] Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias—a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81–2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose–response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death.