New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi.

Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy-quinone core were considered for developing new anti-T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure-activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy-quinones with higher potency against the protozoan parasite T. cruzi.

Design, synthesis, biological evaluation and binding mode modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1.

A series of N-acyl-2,5-dimethoxyphenyl-1H-benzimidazoles were designed based on a CoMFA model for cannabinoid receptor type 1 (CB1) ligands. Compounds were synthesized and radioligand binding affinity assays were performed. Eight novel benzimidazoles exhibited affinity for the CB1 receptor in the nanomolar range, and the most promising derivative compound 5 displayed a K(i) value of 1.2 nM when compared to CP55,940. These results confirm our previously reported QSAR model on benzimidazole derivatives, providing new information for the development of small molecules with high CB1 affinity.

Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques.

BACKGROUND: Prevention and early diagnosis have the greatest potential for public health and are the most effective method in the long-term to control oral cancer. The aim was to apply PAP staining together with AgNOR staining and morphometric analysis in oral exfoliative cytology, to determine the sensitivity and specificity of these methods in the detection of malignant changes for the purposes of both initial population monitoring and follow-up. METHODS: AgNOR, Papanicolau, and morphometric tests were conducted in samples of patients with oral cancer, oral potentially malignant disorders and controls (opposite side of lesions). Specificity and sensitivity values for each stain method and the curve under ROC area were estimated. RESULTS: The diagnostic variables which allowed greatest accuracy in identifying malignancy relative to the healthy control were cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio. CONCLUSIONS: The total number of AgNOR is a reliable marker for detecting neoplastic cells; this method increases sensitivity and specificity by decreasing the likelihood of false negatives or positives, as the accuracy obtained was 90%. It is also a low-cost, non-invasive, simple methodology that can be recommended to help the early detection of oral cancer and monitoring of patients with a first diagnosis of cancer.

Conocimiento sobre riesgos y profilaxis preventiva en estudiantes de odontología / Knowledges about risk and preventive prophylaxis in students of odontology

En la práctica odontológica hay exposición a riesgos biológicos. En este trabajo indagamos: qué conocimientos sobre dichos riesgos tienen los alumnos, pues representan una problemática de morbi-mortalidad a nivel mundial, nacional y local; y si saben cómo prevenirlos y cómo proceder ante un accidente. Se encuestaron 192 estudiantes del último año de la Facultad de Odontología (UNC). El 95% afirmó conocer los riesgos vinculados con enfermedades infectocontagiosas, pero en general no conocen cuáles son. Con respecto a la profilaxis de disposición, las respuestas fueron incorrectas. El 94 % afirmó conocer los procedimientos ante un accidente de trabajo, pero hubo respuestas imprecisas y desconocimiento sobre los protocolos a seguir. De este estudio inferimos que la mayoría de los alumnos no percibe la vinculación entre riesgo- enfermedad, no conoce totalmente los protocolos relacionados a exposición con material biológico e inmunización , ni la conducta a seguir ante accidentes de trabajo en la práctica clínica.

Conocimiento sobre riesgos y profilaxis preventiva en estudiantes de odontología / Knowledges about risk and preventive prophylaxis in students of odontology

En la práctica odontológica hay exposición a riesgos biológicos. En este trabajo indagamos: qué conocimientos sobre dichos riesgos tienen los alumnos, pues representan una problemática de morbi-mortalidad a nivel mundial, nacional y local; y si saben cómo prevenirlos y cómo proceder ante un accidente. Se encuestaron 192 estudiantes del último año de la Facultad de Odontología (UNC). El 95% afirmó conocer los riesgos vinculados con enfermedades infectocontagiosas, pero en general no conocen cuáles son. Con respecto a la profilaxis de disposición, las respuestas fueron incorrectas. El 94 % afirmó conocer los procedimientos ante un accidente de trabajo, pero hubo respuestas imprecisas y desconocimiento sobre los protocolos a seguir. De este estudio inferimos que la mayoría de los alumnos no percibe la vinculación entre riesgo- enfermedad, no conoce totalmente los protocolos relacionados a exposición con material biológico e inmunización , ni la conducta a seguir ante accidentes de trabajo en la práctica clínica.(AU)

Graph models for phenotype and genotype association between oral mucosa and submandibular gland tumorigenesis in rat.

BACKGROUND: In recent years, success of statistics in field of genetics has been the identification of genes that affect the process of disease. Experimental models using animals enable early stages of tumor development to be studied. The aim of this study was to apply graph models to assess the association between the observed phenotypic changes in rat oral mucosa and induced tumorigenesis in the submandibular gland (SMG). MATERIALS AND METHODS: We studied changes in oncogenes TP53 and bcl-2, histopathological and immunomarker variables in samples of oral mucosa and SMG of Wistar male rats, 60 days old and 180 g in weight, in which tumorigenesis was induced in their SMG by a 0.5% solution of 9,10-dimethyl-1,2-benzanthracene in acetone. A set of linear structural equations were defined, with each formula indicating the response variables and the direct influences. In graph models, saliva was considered as a latent variable. The association was analyzed using Graphical Gaussian Markov models and odd ratios. RESULTS: About 40% of animals treated with 9, 10-dimethyl-1, 2-benzanthracene showed histological alterations in the epithelial basal strata of their oral mucosa only at 150 days. Statistical models indicated a relationship between gene alteration in gene bcl-2 in the SMG and histological changes observed in the oral mucosa (P = 0.04). CONCLUSION: Graph statistical model with one latent variable allows to conclude that these results associated with other clinical parameters may be useful in detecting early changes in SMG tumorigenesis. Furthermore, the design of randomized sampling of oral mucosa allows to validate these results and establish a reliable methodology for presumptive diagnosis or screening in the future.