Two-dimensional chromatography for enantiomeric analysis of mitotane and its metabolite o,p'-DDA in patients with adrenocortical carcinoma indicates enantioselective metabolism.

Mitotane is a chiral drug used to treat adrenocortical carcinoma, being metabolized to the o,p'-dichlorodiphenyl acetic acid (o,p'-DDA), also a chiral compound. Despite of its therapeutic significance, the overall ratios and enantiomers have not been known. In this study, we analyzed the enantiomers of mitotane and o,p'-DDA in the plasma of patients by a newly developed chiral-phase method employed in two-dimensional chromatography. Important differences were observed in the ratio of (S)/(R)-mitotane, which varied substantially from 1:1.2 to 1:10 whereas the (S)/(R)-o,p'-DDA ratio was relatively conserved, at approximately 2:1. These findings provide evidence for the enantioselective metabolism and provide a method for further analyses of mitotane and metabolites, which can explain the variation in the therapeutic response.

Can high- and low-temperature thermal stress modulate the antioxidant defense response of Astyanax lacustris brain?

Change in temperature of aquatic environment have impacts on the physiology of fish, especially in the brain, which is a vital organ and prone to oxidative damage. Astyanax lacustris is a freshwater fish that play an important role in the food market and has been increasingly used in fish farms, besides environmental monitoring studies. Therefore, this study aimed to evaluate the responses of antioxidant biomarkers and products of the oxidative process in the brains A. lacustris subjected to thermal shock. The specimens were obtained from artificial farming lakes and subjected to shock induced by exposure to high (31 °C ± 0.5) and low (15 °C ± 0.5) temperature for 2, 6, 12, 24, 48, 72 and 96 h; control group were maintained at 23 °C ± 0.5. At 31 °C, glutathione-related enzymes were more responsive, suggested by the change activity of GPx and G6PDH enzymes, in addition to GSH levels. At 15 °C, enzymes of the first line of defense were more active, evidenced by the change CAT activity. No significant changes were detected in the levels of ROS, LPO and PCO. These results indicate that the brains of A. lacustris have an efficient antioxidant defense system with the ability to acclimatize to the temperatures tested.

Tissue Proteases and Immune Responses: Influencing Factors of COVID-19 Severity and Mortality.

The coronavirus disease 19 (COVID-19) is caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected the global population despite socioeconomic status and amazed surveillance agencies for its incidence, mortality, and recovery rates. COVID-19 affects all age groups; however, it is suggested to progress into severe disease and cause mortality in over 10% of the confirmed cases, depending on the individual characteristics of the affected population. One of the biggest unanswered questions it is why only some individuals develop into the severe stages of the disease. Current data indicate that most of the critically ill are the elderly or those with comorbidities such as hypertension, diabetes, and asthma. However, it has been noted that, in some populations, severe disease is mostly observed in much younger individuals (<60-years old) with no reported underlying medical conditions. Certainly, many factors may contribute to disease severity including intrinsic host factors such as genetic variants, the expression levels of tissue proteins, among others. Considering all these aspects, this review aims to discuss how the expression levels of tissue proteases and the different profiles of immune responses influence the susceptibility to COVID-19 as well as disease severity and outcome.