Diagnosis of syphilis remains a challenge because of the multiform and polymorphous clinical pattern at onset and its ability to imitate different diseases. It is mandatory to include syphilis in the differential diagnosis of unusual oral lesions. Diagnosis of oral lesions of syphilis is often difficult, and biopsy is required in controversial cases.
The current treatments for leishmaniasis are unsatisfactory due to their toxic side effects, high costs, and increasing problems with drug resistance. Thus, there is an urgent need for alternative drugs against leishmaniasis. Different approaches have been used to identify novel pharmacophores against Leishmania sp. parasites, and one strategy has been the analysis of naturally occurring plant-derived compounds, including naphthylisoquinoline alkaloids. In the present study, we examined the abilities of these alkaloids to inhibit the growth of Leishmania major promastigotes and evaluated their effects on macrophages, dendritic cells, and fibroblasts. Furthermore, we determined the efficacy of selected compounds in decreasing the infection rate of macrophages and regulating their production of cytokines and nitric oxide. Our results demonstrate that the naphthylisoquinoline alkaloids ancistrocladiniums A and B (compounds 10 and 11) and the synthetic isoquinolinium salt (compound 14) were effective against intracellular amastigotes in the low submicromolar range, while toxicity against mammalian cells was observed at concentrations that were significantly higher than those needed to impair parasite replication. The activities of compounds 11 and 14 were mainly directed against the amastigote stage of L. major. This effect was not associated with the stimulation of host macrophages to produce nitric oxide or secrete cytokines relevant for the leishmanicidal function. In conclusion, our data suggest that ancistrocladiniums A and B (compounds 10 and 11) and the synthetically prepared isoquinolinium salt (compound 14) are promising candidates to be considered as lead compounds for leishmanicidal drugs.
Background The prevalence of malocclusion, temporomandibular disorders (TMD) and oral parafunctions is highly debated in children population. Objectives To investigate the prevalence of malocclusion, self‐reported oral parafunctions and TMD‐pain in Italian schoolchildren and to assess the association between the examined factors. Methods A total of 700 children aged 9‐11 years were selected among six public schools in Campania region (Italy). Molar relationship, overjet, overbite and cross‐bite were assessed through a clinical examination. Furthermore, the subjects were demanded to fill in a validated questionnaire for TMD‐pain screening and the short form of the Oral Behaviours Checklist. Descriptive statistics were used to report the frequencies. The associations between occlusal traits, oral parafunctions and TMD‐pain were analysed with a Pearson chi‐square test, as expressed by odds ratio and 95% confidence intervals. The significance level was set at P < 0.05. Results Molar Class I was the most frequently encountered molar relationship, followed by molar Class II, subdivision and molar Class III. Increased overjet was more common than negative overjet. Posterior cross‐bite was observed in 12% of children. TMD‐pain was recorded in 14.7% of subjects. High frequency of oral parafunctions was reported in 21.3% of subjects. A significant association was found between TMD‐pain and negative overbite. Cross‐bite and high frequency of oral parafunctions were associated with TMD‐pain. Conclusion The current results show that malocclusion, self‐reported oral parafunctions and TMD‐pain are frequent findings among Italian schoolchildren and that some occlusal factors and high frequency of oral parafunctions might be associated with TMD‐pain.
Chemotherapy of leishmaniasis is mainly based on antimonials. However, they are extremely toxic and cause serious side effects, and there is a worldwide increasing frequency of chemoresistance to antimonials. These issues emphasize the urgent need for affordable alternative drugs against leishmaniasis. Leishmania cysteine proteases are essential for parasite growth, differentiation, pathogenicity, and virulence and are thus attractive targets for combating leishmaniasis. Herein we demonstrate that the cysteine protease inhibitors aziridine-2,3-dicarboxylates 13b and 13e impaired promastigote growth at mid-micromolar concentrations and decreased the infection rate of peritoneal macrophages at concentrations 8-to 13-fold lower than those needed to inhibit parasite replication. Simultaneous treatment of infected cells with compound 13b and gamma interferon resulted in an even further reduction of the concentration needed for a significant decrease in macrophage infection rate. Notably, treatment with the compounds alone modulated the cytokine secretion of infected macrophages, with increased levels of interleukin-12 and tumor necrosis factor alpha. Furthermore, the decreased infection rate in the presence of compound 13b correlated with increased nitric oxide production by macrophages. Importantly, at the concentrations used herein, compounds 13b and 13e were not toxic against fibroblasts, macrophages, or dendritic cells. Together, these results suggest that the aziridine-2,3-dicarboxylates 13b and 13e are potential antileishmanial lead compounds with low toxicity against host cells and selective antiparasitic effects.
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