Methazolamide

Reactive oxygen species (ROS) are generated as byproducts of oxygen metabolism and play multiple roles in biol. systems.In addition, these species can be generated in the eye as a result of the photosensitizing action of pigments that are naturally present in this organ, such as riboflavin.An imbalance between the production of ROS and the response of the antioxidant defense system results in oxidative stress.In humans, the oxidative stress can lead to the initiation or development of many ocular diseases and injuries (glaucoma, cataracts, macular degeneration).In this highly oxidative cellular environment, topically administered drugs for the treatment of various pathologies may be susceptible to be attacked by ROS and consequently degraded, losing their clin. efficacy or generating toxic products.In this contribution, the kinetics of ROS-mediated degradation of the antiglaucoma drugs, acetazolamide and methazolamide, was investigated.In order to analyze the effects that these drugs and their derivatives produce on the viability of normal human cells, this parameter was evaluated in the MRC-5 line.Results showed that acetazolamide and methazolamide interact with the electronic triplet state of riboflavin and with different photo-generated ROS from this state.Both drugs were chem. degraded by singlet oxygen, although methazolamide was more reactive than acetazolamide.The experiments demonstrated that neither the drugs nor their ROS-mediated oxidation products exhibited cytotoxicity in the MRC-5 cell line.On the other hand, under direct UV irradiation, AZ and MZ generated O₂(¹Δ_g) with considerable efficiency compared to other ophthalmic drugs and would be considered good sensitizers.

Sepsis is a non-discriminatory inflammatory reaction that can result in a diverse array of organ dysfunctions, which can be fatal. Pyroptosis is a programmed mechanism of cell death that is distinguishable from apoptosis and other forms of cellular demise. However, the role of pyroptosis in sepsis remains to be further explored. In this study, by employing a combination of the difference analysis, WGCNA, Friends' analysis, and machine learning, the central gene S100A12 was successfully identified. S100A12 demonstrated superb diagnostic capabilities in both the integrated and external validation datasets. Furthermore, significant disparities were observed in the levels of monocytes, eosinophils, and neutrophils between sepsis patients and the control group, as per the findings of immune infiltration analysis. The aforementioned immune infiltrating cells exhibited an increase in expression levels among patients diagnosed with sepsis and were found to be significantly and positively associated with S100A12 expression. The results of the single-cell analysis indicated a significant expression of S100A12 in both neutrophils and monocytes, which was in complete alignment with the outcomes of immune infiltration. In summary, the pyroptosis-related gene S100A12 represents a potential biomarker for the diagnosis and treatment of sepsis.