Amelanotic melanoma of the skin – detailed review of the problem

BackgroundMalignant melanoma (MM) of the skin accounts for about one per cent of all malignancies in humans. Amelanotic melanoma is a rare tumour, diagnosed in eight per cent of all melanomas.AimsThe study aimed to analyse our clinical experience with amelanotic MM of the skin and the statistical data from a retrospective five year analysis of pigmented and amelanotic types of skin melanoma. Furthermore, we compare our results to those from other teams' studies. To reach the corresponding in-depth conclusions.MethodsThe study included 151 patients with malignant melanoma of the skin, diagnosed and treated at Dr. Georgi Stranski University in Pleven, Bulgaria, between 2012 and 2016. All the patients signed informed consent forms.ResultsOf the 151 patients we studied, 14 (9.3 per cent) were diagnosed with amelanotic melanoma. The average Breslow thickness in patients with amelanotic MM was 4.2mm, while in pigmented MM patients it 2.1mm. Local recurrence rates (35.7 per cent) were higher in patients with amelanotic melanoma. Distant metastases were found in 39 of all tested patients with melanoma. Of the 14 patients with amelanotic MM, eight had such metastases.ConclusionAmelanotic melanoma was diagnosed too late. Local recurrences were six times as many as the ones diagnosed in pigment melanoma. Distant metastases were twice as many, and mortality rates were three times higher

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