ABSTRACT
Persistent human papillomavirus (HPV) infection is closely associated with cervical carcinoma. Co-infection in the endocervical environment with other microorganisms, such as Chlamydia trachomatis, may increase the risk of HPV infection and neoplastic progression. While in some individuals, Chlamydia trachomatis infection is resolved with the activation of Th1/IFN-γ-mediated immune response, others develop a chronic infection marked by Th2-mediated immune response, resulting in intracellular persistence of the bacterium and increasing the risk of HPV infection. This work aimed to quantify cytokines of the Th1/Th2/Th17 profile in exfoliated cervix cells (ECC) and peripheral blood (PB) of patients positive for Chlamydia trachomatis DNA, patients positive for Papillomavirus DNA, and healthy patients. Cytokine levels were quantified by flow cytometry in ECC and PB samples from patients positive for C. trachomatis DNA (n = 18), patients positive for HPV DNA (n = 30), and healthy patients (n = 17) treated at the Hospital de Amor, Campo Grande-MS. After analysis, a higher concentration of IL-17, IL-6, and IL-4 (p <0.05) in ECC; INF-γ and IL-10 (p <0.05) in PB was found in samples from patients positive for C. trachomatis DNA compared to samples from healthy patients. When comparing samples from patients positive for HPV DNA, there was a higher concentration of cytokines IL-17, IL-10, IL-6, and IL-4 (p <0.05) in ECC and IL-4 and IL-2 (p <0.05) in PB of patients positive for C. trachomatis DNA. These results suggest that induction of Th2- and Th17 mediated immune response occurs in patients positive for C. trachomatis DNA, indicating chronic infection. Our results also demonstrate a high concentration of pro-inflammatory cytokines in ECC of patients positive for C. trachomatis DNA.
Subject(s)
Chlamydia Infections , Papillomavirus Infections , Female , Humans , Chlamydia trachomatis/genetics , Human Papillomavirus Viruses , Interleukin-10 , Interleukin-17 , Interleukin-6 , Interleukin-4 , Persistent Infection , Chlamydia Infections/microbiology , Cytokines , Papillomaviridae/geneticsABSTRACT
In a search for new antitrypanosomal agents in the Brazilian flora, the ethanol extract of the xylopodium from Aiouea trinervis (Lauraceae) exhibited in vitro activity against the epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas disease. Bioassay-guided chromatographic fractionation of the ethanol extract afforded three butanolides, isoobtusilactone A (1), epilitsenolide C2 (2), and epilitsenolide C1 (3). Butanolides 1 and 3 were more active against T. cruzi epimastigotes than the reference drug benznidazole (by 8.9-fold and 3.2-fold, respectively), while 2 proved inactive. Compounds 1 and 3 showed low cytotoxicity in mammalian Vero cells (CC50> 156 µmol L-1) and high selectivity index (SI) values for epimastigotes (SI = 56.8 and 28.6, respectively), and 1 was more selective than benznidazole (SI = 46.5). Butanolide 1 at 24 µmol L-1 also led to cell cycle alterations in epimastigote forms, and inhibited the growth of amastigote cells in more than 70 %. In silico ADMET properties of 1 were also analyzed and predicted favorable drug-like characteristics. This butanolide also complied with Lipinski's rule of five and was not predicted as interference compound (PAINS). This is the first report on the isolation of these bioactive butanolides under the guidance of in vitro trypanocidal activity against T. cruzi.
ABSTRACT
Human Papillomavirus (HPV) has considerable tropism for epithelial and mucosal tissues and can therefore be found in several anatomical sites, including the oral cavity. This study aimed to investigate the presence of HPV-DNA and the most frequent viral types in patients using full dentures, compare to patients not using full dentures and to associate its presence with socio-epidemiological and behavioral factors. The study consisted of 90 patients with or without full dentures at the time of collection, treated at a public dental clinic. The samples were obtained by exfoliating the oral cavity, and analyzed for HPV-DNA using the nested PCR with PGMY09/11 (450-bp), and general primers GP5+/GP6+ (150-bp). Genotyping was performed by specific-type PCR to HPV 6, 11, 16, 18, 31, 33, and 45; and Restriction Fragment Length Polymorphism (RFLP). Pearson's Chi-square test (x 2 ) or Fisher's exact test were applied and significant variables in these tests were analyzed by multinomial logistic regression analysis to estimate odds ratio (OR). HPV-DNA was detected in 27.7% of samples and, among those obtained from patients using full dentures, positivity for HPV-DNA was 41.9% (p = 0.025). The most frequent viral types were low-risk HPV 6 and 11, and high-risk HPV 31 and 45. Patients who used full dentures had an odds ratio of 2.1 to be positive for HPV DNA. Our results indicate the need for periodic dental follow-up of patients with full dentures in order to preserve the basic conditions of oral health, and also to monitor the appearance of lesions with malignant potential.