Isoprostanes and asthma

Isoprostanes are prostaglandin (PG)-like compounds generated in vivo following oxidative stress by non-enzymatic peroxidation of polyunsaturated fatty acids, including arachidonic acid. They are named based on their prostane ring structure and by the localization of hydroxyl groups on the carbon side chain; these structural differences result in a broad array of isoprostane molecules with varying biological properties. Generation of specific isoprostanes is also regulated by host cell redox conditions; reducing conditions favor F₂-isoprostane production while under conditions with deficient antioxidant capacity, D₂- and E₂-isoprostanes are formed. F₂-isoprostanes (F₂-isoP) are considered reliable markers of oxidative stress in pulmonary diseases including asthma. Importantly, F₂-isoP and other isoprostanes function as ligands for PG receptors, and potentially other receptors that have not yet been identified. They have been reported to have important biological properties in many organs. In the lung, isoprostanes regulate cellular processes affecting airway smooth muscle tone, neural secretion, epithelial ion flux, endothelial cell adhesion and permeability, and macrophage adhesion and function. In this review, we will summarize the evidence that F₂-isoP functions as a marker of oxidative stress in asthma, and that F₂-isoP and other isoprostanes exert biological effects that contribute to the pathogenesis of asthma. This article is part of a Special Issue entitled Biochemistry of Asthma.     

Synthesis of novel arylpyrazolo corticosteroids as potential ligands for imaging brain glucocorticoid receptors

Corticosteroids regulate a variety of essential physiological functions, such as mineral balance and stress. The great interest in these steroids, especially the glucocorticoids, stems from roles they are thought to play in neuropsychiatric disorders, such as severe depression and anxiety.The development of glucocorticoid receptor (GR) ligands which are appropriately labeled with short-lived positron-emitting radioisotopes would allow the non-invasive in-vivo imaging and mapping of brain GRs by means of positron emission tomography (PET). In this context we have synthesized a series of novel arylpyrazolo steroids exhibiting different substitution patterns at the D-ring of the steroid skeleton, as ligands for brain GRs. Special attention was given to 4-fluorophenyl pyrazolo steroids, which are known to display high binding affinity toward the GR. The compounds were evaluated in a competitive radiometric receptor binding assay to determine their relative binding affinities (RBA) to the GR. Some compounds show good binding affinities of up to 56% in comparison to dexamethasone (100%). In initial experiments, selected candidates were labeled with the positron emitter fluorine-18 and in one case with the gamma-emitter iodine-131.     

TMT‐Based Proteomics Profiling of Bovine Liver Underscores Protein Markers of Anabolic Treatments

Illegal use of growth promoter compounds in food production exposes consumers to health risk. Surveillance of such practices is based on direct detection of drugs or related metabolites by HPLC‐MS/MS. Screening strategies focusing on indirect biological responses are considered promising tools to improve surveillance. In this study, an untargeted shotgun proteomics approach based on tandem mass tags (TMTs) is carried out to identify proteins altered in bovine liver after different anabolic treatments. Three controlled pharmacological treatments with dexamethasone, a combination of dexamethasone and clenbuterol, or a combination of sexual steroids (trenbolone and estradiol) are analyzed. Untargeted TMT analysis of liver digests by high resolution MS allowed for the relative quantification of proteins. Thanks to partial least squarediscriminant analysis, a set of proteins capable to classify animals treated with dexamethasone alone (11 proteins), or in combination with clenbuterol (13 proteins) are identified. No significant difference is found upon administration of sexual steroids. After relative quantification of candidate markers by parallel reaction monitoring (PRM), two predictive models are trained to validate protein markers. Finally, an independent animal set of control bulls and bulls treated with dexamethasone is analyzed by PRM to further validate a predictive model giving an accuracy of 100%.     

Activity Monitoring of the Inhabitants in Tauwema,a Traditional Melanesian Village: Rest/Activity Behaviour of Trobriand Islanders (Papua New Guinea)

The inhabitants of Tauwema village represent a traditionally living society. Altogether, 39 inhabitants belonging to seven families were included in this study. Families or people living in one household were preferentially chosen for monitoring particularly the effects of social zeitgebers and synchronization within families. They were observed continuously for 7 consecutive days using microelectronic actometers that register locomotor activity with a sampling period of 2 minutes and a resolution of 7 bit. The activity data obtained showed that in young infants circadian patterns develop out of ultradian components dominating in the first months of life. The rhythmicity of the adults was well-related to the natural light-dark cycle, combined with a strong social component which is reflected in a comparatively small intra- and inter-individual variability in the time of the end of the main sleep span in the morning, while the variability in the beginning of the main sleep period in the evening is much greater. The mean sleep duration of the younger infants (up to 11 months; n =4) varied between 9 and 12 h per day and that of the adults (n = 23) between 7 and 10 h. Gender-specific differences occurred in married couples with wives having a longer sleep duration in 7 out of 9 cases.     

Management of recurrent apthous ulcer using Corticosteroids,Local anesthetics and nutritional supplements

Recurrent Aphthous ulcers are the most common oral lesions among dental patients. The ulcers, which usually occur on the nonkeratinized oral mucosa, can cause considerable pain and may interfere with eating, speaking, and swallowing. Therefore, it is of interest to report data on the management of recurrent aphthous ulcer using corticosteroids, local anesthetics and nutritional supplements. Case sheets of 76 patients who underwent treatment for recurrent aphthous ulcer between June 2019 and March 2020 at the Saveetha Dental College, India were used in this analysis. Data was analyzed using Chi square test at a P value < 0.05 that is statistically significant. Results show that topical anaesthetics in population (49%) were more effective that corticosteroids. Thus, topical anaesthetics are recommended for recurrent aphthous ulcer.