In Vivo Toxicity, Redox-Modulating Capacity and Intestinal Permeability of Novel Aroylhydrazone Derivatives as Anti-Tuberculosis Agents.

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.

Beneficial effects of the fructus Sophorae extract on experimentally induced osteoporosis in New Zealand white rabbits.

Sophora japonica is a source of several flavonol, flavone and isoflavone glycosides that are reported to positively affect menopausal symptoms including osteoporotic complications. In the present study fructus Sophorae extract (FSE) was administered orally for three months at a dose of 200 mg kg-1 in ovariectomized (OVX) New Zealand rabbits. 3D computed tomography scans and histopathological images revealed microstructural disturbances in the bones of the castrated animals. FSE recovered most of the affected parameters in bones in a manner similar to zoledronic acid (ZA) used as a positive control. The aglycones of the main active compounds of FSE, daidzin, and genistin, were docked into the alpha and beta estrogen receptors and stable complexes were found. The findings of this study provide an insight into the effects of FSE on bone tissue loss and suggest that it could be further developed as a potential candidate for the prevention of postmenopausal osteoporotic complications.

In Vitro Comparison of Several Methods for Initial Proximal Caries Detection.

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%, speci-ficity 93%-94%, sensitivity of DIAGNOdent with proximal surfaces in contact 88%-91%, specificity 79%-89%, sensitivity of DIAG-NOdent directly 89%-92.5%, specificity 81.29%-93%. The highest diagnostic accuracy, increasing with the rise of the level of demin-eralization, 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.

Bone protective effects of purified extract from Ruscus aculeatus on ovariectomy-induced osteoporosis in rats.

Ruscus aculeatus is a source of steroidal saponins that could mimic sex hormones and could help alleviate the risk of fracture in osteoporotic patients. The aim of the present study was to evaluate the in vitro effects of an extract from R. aculeatus (ERA) on the proliferation of human osteoblast-like SaOS-2 cell line and to investigate the effects of the ERA administered orally for 10 weeks at three doses (50, 100 and 200 mg/kg) on the bone structure of rats with estrogen deficiency induced by bilateral ovariectomy. Bone turnover markers, hormones, histopathological and radiological disturbances were evidenced in the ovariectomized rats. ERA recovered most of the affected parameters in a dose-dependent manner similar to diosgenin and alendronate used as positive comparators. The main active compounds of ERA (ruscogenin and neoruscogenin) were docked into the Vit. D receptor and oestrogen receptors alpha and beta, and stable complexes were found with binding scores equal to those of estradiol and diosgenin. The findings of this study provide for the first time an insight into the effects of ERA on bone structure and suggest that ERA could be developed as a potential candidate for the prevention of postmenopausal osteoporotic complications.