The emergence and spread of Mycobacterium tuberculosis strains resistant to many or all anti-tuberculosis (TB) drugs require the development of new compounds both efficient and with minimal side effects. Structure-activity-toxicity relationships of such novel, structurally diverse compounds must be thoroughly elucidated before further development. Here, we present the aroylhydrazone compounds (3a and 3b) regarding their: (i) acute and subacute toxicity in mice; (ii) redox-modulating in vivo and in vitro capacity; (iii) pathomorphology in the liver, kidney, and small intestine tissue specimens; and (iv) intestinal permeability. The acute toxicity test showed that the two investigated compounds exhibited low toxicity by oral and intraperitoneal administration. Changes in behavior, food amount, and water intake were not observed during 14 days of the oral administration at two doses of 1/10 and 1/20 of the LD50. The histological examination of the different tissue specimens did not show toxic changes. The in vitro antioxidant assays confirmed the ex vivo results. High gastrointestinal tract permeability at all tested pH values were demonstrated for both compounds. To conclude, both compounds 3a and 3b are highly permeable with low toxicity and can be considered for further evaluation and/or lead optimization.
Introduction: Initial proximal caries is both diagnostic and therapeutic challenge. The disadvantages of the conventional methods for caries detection and the development of technologies led to the creation of contemporary optical devices for early caries detection. Aim: In vitro comparison of the diagnostic accuracy of several methods for early proximal caries detection – visual-tactile, bitewing radiography and laser fluorescence device (DIAGNOdent pen). Materials and methods: Fifty-eight proximal surfaces of extracted human permanent premolars and molars were examined by two examiners using visual inspection, bitewing radiography, DIAGNOdent with proximal contact, and DIAGNOdent directly in the lesion. Results were compared with the histological gold standard. Statistical analysis with ROC curve, sensitivity, specificity and diagnostic accuracy of each detection method was performed. Analysis was conducted in 3 diagnostic thresholds – initial, developed and advanced demineralization. Results: Sensitivity of visual inspection was 16%–33%, specificity 93.3%–100%, sensitivity of bitewing radiography 54%–67%, specificity 93%–94%, sensitivity of DIAGNOdent with proximal surfaces in contact 88%–91%, specificity 79%–89%, sensitivity of DIAGNOdent directly 89%–92.5%, specificity 81.29%–93%. The highest diagnostic accuracy, increasing with the rise of the level of demineralization, was shown by DIAGNOdent directly, followed by DIAGNOdent with proximal contact, bitewing radiography, and visual inspection with the lowest accuracy. Conclusion: The use of contemporary diagnostic devices significantly increases the possibility for early detection of proximal lesions. DIAGNOdent can be used as an adjunct to and increasing the diagnostic accuracy of the conventional caries detection methods.
1 January 2020 in Acta Ichthyologica Et Piscatoria