IMMUNOSUPPRESIVE EFFECTS OF THE METHANOLIC EXTRACT OF CHRYSOPHYLLUM CAINITO LEAVES ON MACROPHAGE FUNCTIONS.

BACKGROUND: The aim of this work was to evaluate the immunomodulatory effect of the methanol extract (MeOH) from Chrysophyllum cainito leaves on the MΦs functions. MATERIAL AND METHODS: Peritoneal murine MΦs isolated from Balb/c mice were treated with the MeOH extract and stimulated with LPS. The effect on the phagocytosis was evaluated by flow cytometry assay. The nitric oxide (NO) and hydrogen peroxide (H2O2) production was measured by the Griess reagent and phenol red reaction, respectively. Levels of IL-6 and TNF-α was measured using an ELISA kit. Viability of MΦs and Vero cells was determined by the MTT method. RESULTS: The MeOH extract of C. cainito leaves inhibited significantly the phagocytosis, and decreased IL-6 and TNF-α production as well as NO and H2O2 released by the MΦs, in a concentration-dependent manner. In addition, MeOH extract of C. cainito showed low cytotoxicity effect against the cells. CONCLUSION: These results suggest that MeOH extract of C. cainito leaves has an immunosuppressive effect on murine MΦs, without effects on cell viability. GC-MS chromatogram analysis of MeOH extract showed that lupeol acetate and alpha-amyrin acetate are the principal compounds.

Synthesis of nitro(benzo)thiazole acetamides and in vitro antiprotozoal effect against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis.

We synthesized four 5-nitrothiazole (1-4) and four 6-nitrobenzothiazole acetamides (5-8) using an easy two step synthetic route. All compounds were tested in vitro against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis, showing excellent antiprotozoal effects. IC50's of the most potent compounds range from nanomolar to low micromolar order, being more active than their drugs of choice. Compound 1 (IC50=122 nM), was 44-times more active than Metronidazole, and 10-fold more effective than Nitazoxanide against G. intestinalis and showed good trichomonicidal activity (IC50=2.24 µM). This compound did not display in vitro cytotoxicity against VERO cells. The in vitro inhibitory effect of compounds 1-8 and Nitazoxanide against G. intestinalis fructose-1,6-biphosphate aldolase (GiFBPA) was evaluated as potential drug target, showing a clear inhibitory effect over the enzyme activity. Molecular docking of compounds 1, 4 and Nitazoxanide into the ligand binding pocket of GiFBPA, revealed contacts with the active site residues of the enzyme. Ligand efficiency metrics of 1 revealed optimal combinations of physicochemical and antiprotozoal properties, better than Nitazoxanide.

MTHFR/p53 polymorphisms as genetic factors for cervical intraepithelial neoplasia and cervical cancer in HPV-infected Mexican women.

We performed a case-control association study to evaluate the association between common polymorphisms in MTHFR (C677T and A1298C) and the Arg72Pro polymorphism in the p53 gene and the risk for cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC) in Mexican HPV-infected women. We included 131 women with diagnosis of CIN grade I-II and 78 with CIN III or ICC; as controls we also included 274 women with normal Pap smear and negative HPV test. Genotyping for MTHFR and p53 polymorphisms was performed by PCR-RFPLs. HPV was tested by Hybrid Capture II. Odds ratios and 95% confidence intervals were estimated. Genotype frequencies for the 3 studied polymorphisms were distributed according to the Hardy-Weinberg equilibrium. The A1298C-MTHFR polymorphism showed significant differences for the heterozygous AC genotype and the C allele, whereas the AA genotype and A allele resulted to be genetic risk factors for CIN or ICC (p<0.03). The Arg72Pro-p53 polymorphism showed for the genotypes Arg/Pro and Pro/Pro, and for the Pro allele, a significant association only to the risk for CIN (p<0.03). The MTHFR/p53 interaction showed that the genotype combinations AA/ArgArg and AA/ArgPro were associated, respectively, to the risk of ICC and CIN (p<0.05). This study suggests that the A1298C-MTHFR polymorphism contributes to the genetic risk for both CIN and ICC, whereas the Arg72Pro-p53 polymorphism only contributes to the risk for CIN. The MTHFR/p53 genetic combinations AA/ArgArg and AA/ArgPro are associated genetic risk factors for ICC and CIN in Mexican HPV-infected women.

Multifocal epithelial hyperplasia in a community in the Mayan area of Mexico.

BACKGROUND: Multifocal epithelial hyperplasia is a pathology of the oral mucosa which has been reported in diverse ethnic groups. Human papillomavirus (HPV) types 13 and 32 DNA has been detected in these lesions. The aims of this paper are to describe the epidemiological and clinical characteristics of an outbreak in a rural community in the Mayan area of Mexico and to identify a possible route of transmission through saliva. METHODS: A cross-sectional study was conducted in Chemax (Yucatan, Mexico). Clinical and epidemiological data were obtained through direct interviews. Samples of oral cells and saliva were taken. HPV 13 and 32 were identified by polymerase chain reaction using specific primers. RESULTS: A total of 57 patients were studied, of whom 79.1% were aged <15 years, 38.6% were male, and 61.3% were female. The duration of lesions ranged from one month to 50 years. Lesions were located on the lips, jugal mucosa, and more frequently, the tongue. HPV 13 was found in all the patients and HPV 32 in none. A total of 42 saliva samples were positive for HPV 13. CONCLUSIONS: Human papillomavirus type 13 is involved in multifocal epithelial hyperplasia among the Mexican Mayan population. The presence of HPV 13 in cells from saliva, combined with poor hygiene behaviors, may explain the familial distribution of the pathology.