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2.
Front Oncol ; 12: 948471, 2022.
Article in English | MEDLINE | ID: mdl-36338730

ABSTRACT

Objective: Cervical cancer is one of the deadliest cancers among women in Latin America and Caribbean (LAC), where most of the countries have not been successful in implementing population-level cytology-based screening programs. An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human papillomavirus (HPV) screening. Therefore, this work aims to summarize recent HPV self-sampling approaches in LAC. Method: We performed a systematic review to identify studies focused on "Self-sampling", and "Human Papillomavirus DNA test" and "Latin America" in PubMed, Embase, Web of Science, Cochrane library and SCOPUS databases for publications dating between 01 January 2017 and 15 March 2022 based on the Preferred Reporting Items for systematic reviews and meta-analysis (PRISMA) statement. Additionally, the references of the articles were carefully reviewed. Results: Of the 97 records selected, 20 studies including 163,787 participants, with sample sizes for individual studies ranging from 24 to 147,590 were included in this review. Studies were conducted in 10 LAC countries (18.5%), most with upper medium-income economies (70%). The range of age was 18 to ≥65 years. The vast majority of the studies (85%) addressed the HPV self-sampling strategy for primary cervical cancer screening with overall success for all women including under/never screened and those from special populations (rural, indigenous and gender minorities). Women generally found HPV self-sampling highly acceptable regardless of age, setting of collection, target population or country of residence. Conclusions: HPV self-sampling is a promising strategy to overcome the multiple barriers to cervical cancer screening in LAC settings and increasing attendance in underscreened women in countries/territories with well-established screening programs. Furthermore, this strategy is useful even in LAC countries/territories without organized cervical cancer screening and in special populations such as indigenous, rural and transgender women. Therefore, the information generated by the recent initiatives for HPV self-sampling approach in LAC can be beneficial for decision-making in both new and existing programs in the region.

3.
Asian Pac J Cancer Prev ; 23(5): 1741-1751, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35633560

ABSTRACT

OBJECTIVE: Breast cancer (BC) currently has no effective treatment especially for the highly aggressive and metastatic triple negative breast cancer (TNBC). Here, we investigated the antitumoral and antimigratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against TNBC cell line MDA-MB-231 compared to a nontumorigenic human breast ductal cell line (MCF-10A). METHODS: The phototoxicity/cytotoxicity was assessed by MTT assay, long-term cytotoxicity by clonogenic assay, cell uptake, subcellular distribution, and cellular oxidative stress by fluorescence microscopy, cell death with annexin V-FITC/propidium iodide, PDT mechanism using sodium azide and D-mannitol, and cell migration by wound-healing assay. RESULTS: The treatment promoted phototoxic effect on tumor cell line in a dose-dependent and selective manner. Internalization of F127/HYP was efficient and accumulation occurred in the endoplasmic reticulum and mitochondria, resulting in cellular oxidative stress mainly by the type II mechanism, induced by necrosis. Furthermore, F127/HYP decreased colony formation and reduced the cell migration ability in MDA-MB-231 cells. CONCLUSION: Our results suggest a potentially useful role of F127/HYP micelles as a platform for HYP delivery to more specifically and effectively treat TNBC.


Subject(s)
Perylene , Photochemotherapy , Triple Negative Breast Neoplasms , Anthracenes , Humans , Perylene/analogs & derivatives , Perylene/metabolism , Perylene/pharmacology , Poloxamer , Triple Negative Breast Neoplasms/drug therapy
4.
Pharmaceutics ; 13(12)2021 Dec 02.
Article in English | MEDLINE | ID: mdl-34959339

ABSTRACT

Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases such as cervical cancer. Phthalocyanines (Pcs) are considered good photosensitizers (PS) for PDT, although most of them present high levels of aggregation and are lipophilic. Despite many investigations and encouraging results, Pcs have not been approved as PS for PDT of invasive cervical cancer yet. This review presents an overview on the pathophysiology of cervical cancer and summarizes the most recent developments on the physicochemical properties of Pcs and biological results obtained both in vitro in tumor-bearing mice and in clinical tests reported in the last five years. Current evidence indicates that Pcs have potential as pharmaceutical agents for anti-cervical cancer therapy. The authors firmly believe that Pc-based formulations could emerge as a privileged scaffold for the establishment of lead compounds for PDT against different types of cervical cancer.

5.
Reprod Biomed Online ; 38(6): 926-937, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30940433

ABSTRACT

RESEARCH QUESTION: Is there an association between the presence of sexually transmitted pathogens in the lower (LGT) and upper (UGT) female genital tract with endometriosis and infertility? DESIGN: Case-control study with 60 women submitted to gynaecological laparoscopic surgery. Samples from the UGT and LGT were collected and analysed by single polymerase chain reaction (PCR) for human papillomavirus (HPV) and by multiplex PCR for other sexually transmitted infections (STI). Patients were initially divided into two clinical groups: infertile patients (n = 25) with conjugal infertility and fertile control patients (n = 35). After the surgical findings patients were further divided for additional analysis: an endometriosis group (n = 29) and non-endometriosis control group (n = 31). RESULTS: Sixty per cent of patients were positive for DNA-HPV in some of the genital tract sites sampled. Infertile patients were associated with high-risk HPV (hrHPV) positivity in the UGT sites (P = 0.027). The endometriosis group was associated with hrHPV positivity in the LGT and UGT sites (P = 0.0002 and P = 0.03, respectively). Only hrHPV types were detected in the UGT in both groups. It may be that there is a hrHPV infection continuum, from LGT to UGT, in infertile and endometriosis patients. No association was observed among the other seven STI studied. CONCLUSIONS: This study shows both an association between hrHPV infections in the UGT with infertility and endometriosis, and a possible hrHPV infection continuum, from LGT to UGT. Larger studies are needed to fully investigate the role of hrHPV as a cause of endometriosis and infertility.


Subject(s)
Endometriosis/virology , Infertility, Female/virology , Papillomavirus Infections/complications , Adult , Case-Control Studies , DNA, Viral , Female , Genitalia, Female/virology , Gynecologic Surgical Procedures , Humans , Laparoscopy , Middle Aged , Papillomaviridae , Polymerase Chain Reaction , Risk , Sexually Transmitted Diseases/complications , Sexually Transmitted Diseases/virology , Social Class
6.
Cancer Prev Res (Phila) ; 12(3): 159-170, 2019 03.
Article in English | MEDLINE | ID: mdl-30651294

ABSTRACT

Most cervical cancers occur in women who do not participate in cervical-cancer screening. We therefore evaluated adherence to screening for clinic-based Pap testing, self-collected sampling for HPV testing, and choice of the 2 among 483 unscreened/underscreened women in Brazil. Three public Basic Health Units (BHU) were each randomly assigned to three arms: (i) Pap testing at the BHU (N = 160), (ii) "Self&HPV" (self-collection for HPV testing) (N = 161), and (iii) "Choice" between self-collection and HPV testing and Pap test at the local BHU (N = 162). The theory-based (PEN-3 and Health Belief Model) intervention in all three arms was implemented by trained Community Health Workers (CHW) at participants' home. With the first invitation, 60.0% in the Pap arm, 95.1% [154 of 161 (95.7%) who selected Self&HPV and 0 of 1 (0.0%) who selected Pap] in the Choice arm, and 100% in the Self&HPV arm completed screening. By the second invitation to choose a method of screening in the Choice arm, 100% completed screening. After three invitations, 75.0% of women in the Pap arm completed screening. Adherence to screening differed by study arm (P < 0.001). In conclusion, Self&HPV testing is a promising strategy for unscreened/underscreened women who are recalcitrant or unable to undergo clinic-based cervical screening to complement the screening modality used in the general population. In Brazil, where Pap testing is recommended for routine cervical screening, training CHWs in behavior change strategies and offering Self&HPV or Choice could greatly improve screening population coverage by reaching the unscreened/underscreened populations.


Subject(s)
Diagnostic Self Evaluation , Early Detection of Cancer/methods , Papanicolaou Test/statistics & numerical data , Patient Participation/statistics & numerical data , Specimen Handling/methods , Uterine Cervical Neoplasms/diagnosis , Vaginal Smears/statistics & numerical data , Adult , Early Detection of Cancer/psychology , Female , Follow-Up Studies , Humans , Middle Aged , Papanicolaou Test/psychology , Papillomaviridae/isolation & purification , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Prognosis , Uterine Cervical Neoplasms/psychology , Uterine Cervical Neoplasms/virology , Vaginal Smears/psychology , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/psychology , Uterine Cervical Dysplasia/virology
7.
Nat Rev Urol ; 16(4): 211-230, 2019 04.
Article in English | MEDLINE | ID: mdl-30696994

ABSTRACT

Zika virus (ZIKV) is a re-emerging mosquito-transmitted flavivirus associated with congenital abnormalities in newborns and with Guillain-Barré syndrome in adults. The virus can also be sexually transmitted and can persist in the male genital tract. Studies evaluating the kinetics of ZIKV in seminal shedding of men who have been infected, as well as in animal and cellular models of infection, have shown that, in addition to the testis and epididymis, the prostate and seminal vesicles could also be involved in persistent ZIKV infection. Additionally, some studies have reported that men infected with ZIKV can present with genitourinary symptoms such as haematospermia, prostatitis, painful ejaculation, penile discharge, and oligospermia; however, little is known about the effect of ZIKV on fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is crucial to developing guidelines, effective vaccines, and therapies.


Subject(s)
Genitalia, Male/virology , Semen/virology , Sexually Transmitted Diseases, Viral/diagnosis , Zika Virus Infection/diagnosis , Zika Virus/isolation & purification , Disease Transmission, Infectious , Female , Genital Diseases, Male/diagnosis , Genital Diseases, Male/virology , Humans , Male , Sexually Transmitted Diseases, Viral/transmission , Sexually Transmitted Diseases, Viral/virology , Zika Virus Infection/transmission
8.
Am J Trop Med Hyg ; 100(1): 183-186, 2019 01.
Article in English | MEDLINE | ID: mdl-30398145

ABSTRACT

Zika virus (ZIKV) infection is an emerging public health problem, associated with increased risk for Guillain-Barré syndrome and adverse fetal outcomes, including congenital microcephaly. Zika virus sexual transmission is known, but detection of the virus in different parts of the female reproductive tract is not well established. In this case report, we describe prolonged detection of ZIKV RNA in the vaginal secretion and endocervical mucosa from a Brazilian woman convalescent to ZIKV infection. A viral load of 2 × 102 copies/mL was detected up to 31 days after symptom onset in both samples. Other biological fluids, including whole blood, plasma, serum, urine, and saliva samples, were negative for ZIKV RNA. These findings advance the understanding of ZIKV infection and provide data for additional testing strategies.


Subject(s)
Cervix Mucus/virology , Cervix Uteri/virology , Vagina/virology , Zika Virus Infection/diagnosis , Zika Virus/isolation & purification , Adult , Brazil , Female , Humans , RNA, Viral/analysis , Viral Load
9.
Am J Mens Health ; 12(6): 2104-2115, 2018 11.
Article in English | MEDLINE | ID: mdl-30132409

ABSTRACT

To access the possibility that key markers of bacterial vaginosis (KM-BV) could affect seminal parameters and thus fertility a prospective cohort study was designed (a) to develop rapid and sensitive multiplex polymerase chain reaction (M-PCR) assays to screen 13 key markers of bacterial vaginosis (KM-BV) in semen specimens, (b) to determine the prevalence of KM-BV in semen from randomized male partners of couples seeking fertility evaluation. A total of 229 semen samples were included in the study from males who visited the Sperm Analysis Section of Brazil between October 2015 and March 2016. Eligible men were 18 years or older and had a semen analysis due fertility evaluation (after failing to conceive with their partner after 1 year of unprotected intercourse). Basic seminal parameters were analyzed, and KM-BV was detected by M-PCR assays. M-PCR assays clearly distinguished 13 KM-BV in 146 semen samples (63.8%), mainly Gardnerella vaginalis (50.7%). Some important associations occurred between the presence of KM-BV in semen and changes in seminal parameters. KM-BV is commonly present in the semen of males seeking fertility evaluation and could potentially play significant roles in male subfertility and/or infertility.


Subject(s)
Biomarkers/analysis , Infertility, Male/etiology , Semen Analysis , Sexual Partners , Vaginosis, Bacterial/complications , Adolescent , Adult , Brazil , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction/methods , Prospective Studies , Risk Factors
10.
Front Pharmacol ; 9: 694, 2018.
Article in English | MEDLINE | ID: mdl-30018550

ABSTRACT

Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F2) in cervical cancer cell lines, including HeLa (HPV18-positive), SiHa (HPV16-positive), and C33A (HPV-negative) cells, and also evaluated in vivo anticancer activity. In vitro, cell viability was determined by the MTT assay. Cell migration was determined by the wound healing assay. The mechanism of action was investigated by performing ultrastructural analysis and evaluating reactive oxygen species (ROS) production, mitochondrial metabolism, lipoperoxidation, BCL-2 family expression, caspase expression, and DNA and cell membrane integrity. In vivo activity was evaluated using the murine Ehrlich solid tumor model. F2 time- and dose-dependently reduced cell viability and significantly inhibited the migration of cervical cancer cells. HeLa and SiHa cells treated with F2 (IC50) exhibited intense oxidative stress (i.e., increase in ROS and decrease in antioxidant species) and mitochondrial damage (i.e., mitochondrial membrane potential depolarization and a reduction of intracellular levels of adenosine triphosphate). Increases in the Bax/BCL-2 ratio and caspase 9 and caspase 3 expression, were observed, with DNA damage that was sufficient to trigger mitochondria-dependent apoptosis. Cell membrane disruption was observed in C33A cells (IC50 and IC90) and HeLa and SiHa cells (IC90), indicating progress to late apoptosis/necrosis. The inhibition of ROS production by N-acetylcysteine significantly suppressed oxidative stress in all three cell lines. In vivo, F2 significantly reduced tumor volume and weight of the Ehrlich solid tumor, and significantly increased lipoperoxidation, indicating that F2 also induces oxidative stress in the in vivo model. These findings indicate that the proanthocyanidin polymer-rich fraction of S. adstringens may be a potential chemotherapeutic candidate for cancer treatment.

11.
Anticancer Agents Med Chem ; 18(12): 1750-1760, 2018.
Article in English | MEDLINE | ID: mdl-29866020

ABSTRACT

BACKGROUND: Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of Brazilian green propolis, and possesses, among other things, anticancer properties. However, to the best of our knowledge, there are no studies of artepillin C in cervical cancer. METHOD: To explore a new therapeutic candidate for cervical cancer, we have evaluated the effects of artepillin C on cellular viability in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16- and 18-positive) and C33A (HPV-negative) cells compared to a spontaneously immortalized human epithelial cell line (HaCaT). RESULTS: Our results demonstrated that artepillin C had a selective effect on cellular viability and could induce apoptosis possibly by intrinsic pathway, likely a result of oxidative stress, in all cancer-derived cell lines but not in HaCaT. Additionally, artepillin C was able to inhibit the migration and invasion of cancer cells. CONCLUSION: Thus, artepillin C appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV types.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Neoplasm Invasiveness/prevention & control , Oxidative Stress/drug effects , Phenylpropionates/pharmacology , Propolis/chemistry , Uterine Cervical Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Molecular Structure , Phenylpropionates/chemistry , Phenylpropionates/isolation & purification , Structure-Activity Relationship , Tumor Cells, Cultured , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology
12.
Prog Community Health Partnersh ; 12(1S): 111-119, 2018.
Article in English | MEDLINE | ID: mdl-29755054

ABSTRACT

BACKGROUND: Despite the availability of cervical cancer screening programs in Brazil, some women do not participate in these programs owing to structural and/or interpersonal/intrapersonal barriers, resulting in high cervical cancer incidence and mortality. Integrating community health workers (CHWs) into the delivery of cervical cancer screening interventions is potentially a feasible strategy to address these barriers. OBJECTIVES: This study aimed to implement and evaluate a CHW training to deliver a brief intervention to promote cervical cancer screening among underscreened and unscreened women in Brazil. METHODS: The curriculum addressed cervical cancer and screening, behavioral intervention strategies, and protection of human subjects in research. Pretest and post-test questionnaires assessed changes in CHW objective and perceived knowledge as well as perceived skills and confidence (N = 15). RESULTS: There was a significant increase in objective and perceived knowledge about cervical cancer, behavior change strategies, and protection of human subjects in research between pretest and post-test, but not in self-perception about skills and confidence to motivate women to engage in cervical cancer screening. CONCLUSIONS: Improvements in CHW knowledge about cervical cancer screening and behavior change represents a step forward toward successful interventions, but adaptations are needed to boost their self-confidence and perceived skills with regard to their ability to promote behavior change at the community level.


Subject(s)
Community Health Workers/education , Early Detection of Cancer/methods , Mass Screening/methods , Uterine Cervical Neoplasms/diagnosis , Adult , Aged , Brazil , Capacity Building , Female , Humans , Middle Aged , Women's Health
13.
Urology ; 113: 52-58, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29287977

ABSTRACT

OBJECTIVE: To assess the possibility that herpes simplex virus (HSV) infection could affect seminal parameters, we (1) standardize and validate a multiplex polymerase chain reaction (M-PCR) assay to detect HSV-1 and HSV-2 in semen, and (2) determine the prevalence of HSV-1/-2 in the semen of randomized male partners of couples seeking fertility evaluation. MATERIALS AND METHODS: A total of 279 semen samples were included in the study from men who visited the Sperm Analysis Section of São Camilo Laboratory of Maringá, Brazil, between November 2014 and July 2015. Eligible men were 18 years or older and had a semen analysis due fertility evaluation (after failing to conceive with their partner after 1 year of unprotected intercourse). Basic seminal parameters were analyzed, and HSV-1 and HSV-2 were detected by M-PCR. RESULTS: The M-PCR assay clearly distinguished and identified 2 HSV types in semen samples. HSV in total was detected in 10.7% of samples, of which 7.5% had HSV-1 exclusively and 3.2% had HSV-2 exclusively. We detected a significant association of HSV-2 infection with hematospermia and with a lower mean seminal volume, and between HSV-1 infection and a lower mean sperm count. CONCLUSION: These findings suggest that the male partners of infertile couples with HSV infections may have changes on the 2 equally important components of semen, spermatozoa and seminal fluid, which may influence fertility. Further studies enrolling a larger number of patients are necessary to confirm these data and to elucidate the clinical relevance of HSV presence in semen.


Subject(s)
Herpes Simplex/complications , Infertility, Male/etiology , Semen/virology , Sperm Motility , Adult , Cohort Studies , Herpes Simplex/diagnosis , Humans , Infertility, Male/physiopathology , Male , Middle Aged , Retrospective Studies , Semen Analysis/methods , Severity of Illness Index , Sperm Count/methods
14.
Biomed Res Int ; 2017: 4684629, 2017.
Article in English | MEDLINE | ID: mdl-28835893

ABSTRACT

Several studies have addressed the impact of viral infections on male infertility. However, it is still unknown whether human papillomavirus (HPV) can alter seminal parameters. The aim of this study was to determine the prevalence of HPV in the semen of male partners of couples seeking fertility evaluation. Additionally, we assessed the possibility that HPV infections affect seminal parameters. A total of 229 semen samples were collected from men in the Sperm Analysis Section of São Camilo Laboratory of Maringá, Brazil, between October 2015 and March 2016. Basic seminal parameters were analyzed, and HPV was detected and genotyped by polymerase chain reaction. HPV DNA was detected in 16.6% of samples. Of these, 10.5% had single type HPV infections, 6.1% had multiple HPV infections, 5.7% had exclusively high-risk HPV, and 6.1% had exclusively low-risk HPV. Samples positive for single and multiple types of HPV were associated with abnormal viscosity, and samples positive for multiple HPV types were also associated with hypospermia, higher pH, and increased leukocyte numbers. These findings suggest that the male partners of infertile couples with seminal HPV infections may have prostate disturbances indicative of glandular dysfunction, which may influence fertility.


Subject(s)
Infertility, Male , Papillomavirus Infections , Semen/virology , Adult , Cohort Studies , DNA, Viral/genetics , Humans , Infertility, Male/epidemiology , Infertility, Male/physiopathology , Infertility, Male/virology , Male , Middle Aged , Papillomavirus Infections/epidemiology , Papillomavirus Infections/physiopathology , Papillomavirus Infections/virology , Polymerase Chain Reaction , Semen Analysis/statistics & numerical data , Young Adult
15.
Int Urogynecol J ; 27(5): 773-80, 2016 May.
Article in English | MEDLINE | ID: mdl-26564224

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Acute uncomplicated lower urinary tract infections (UTI) and vulvovaginal candidiasis (VVC) both occur frequently in women. Although VVC is believed to commonly occur after antibiotic therapy, few studies have demonstrated this association. Thus, the aim of the study was to estimate the prevalence of colonization by Candida spp. and VVC after norfloxacin (NOR) use for UTI and the effects on the vaginal microbiota and inflammatory process. METHODS: This was a prospective cohort study of women with culture-proven UTI who were treated with NOR (antibiotic group). The control group consisted of women with noninfectious diseases or in preventive care. Candida vaginal infections were monitored both clinically and mycologically at baseline and at the follow-up evaluation. RESULTS: All women showed UTI remission after NOR treatment, and no woman in either group, antibiotic and control, showed symptoms of VVC. Both groups showed similar ratios of a positive Candida culture at baseline (6.7 % and 12.8 %, respectively) and at follow-up (3.3 % and 8.5 %, respectively) (p = 0.2768 and p = 0.5035, respectively). The antibiotic group showed no increased risk of Candida colonization or VVC after NOR treatment compared with the control group [odds ratio (OR) 0.556, 95 % confidence interval (CI) 0.2407-10.05]. CONCLUSIONS: NOR was effective for UTI treatment, did not increase the risk of vaginal colonization by Candida or VVC, and did not lead to major disturbances of the vaginal microbiota.


Subject(s)
Anti-Bacterial Agents/pharmacology , Candida/isolation & purification , Candidiasis, Vulvovaginal/epidemiology , Microbiota/drug effects , Norfloxacin/pharmacology , Vagina/microbiology , Acute Disease , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Brazil/epidemiology , Case-Control Studies , Colony Count, Microbial , Female , Humans , Middle Aged , Norfloxacin/therapeutic use , Prevalence , Prospective Studies , Urinary Tract Infections/drug therapy , Young Adult
16.
Cancer Epidemiol Biomarkers Prev ; 24(10): 1539-47, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26261088

ABSTRACT

BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis.


Subject(s)
Chlamydia Infections/genetics , GPI-Linked Proteins/genetics , Gene Expression Regulation, Neoplastic , Matrix Metalloproteinase 9/genetics , Papillomavirus Infections/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervicitis/genetics , Adult , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/virology , Cervix Uteri/metabolism , Cervix Uteri/pathology , Chlamydia Infections/metabolism , Chlamydia Infections/pathology , Chlamydia trachomatis/genetics , Cross-Sectional Studies , DNA, Bacterial/genetics , DNA, Neoplasm/genetics , DNA, Viral/genetics , Female , GPI-Linked Proteins/biosynthesis , Gene Expression Regulation, Bacterial , Genotype , Human papillomavirus 16/genetics , Humans , Immunohistochemistry , Matrix Metalloproteinase 9/biosynthesis , Papanicolaou Test , Papillomavirus Infections/metabolism , Papillomavirus Infections/virology , Real-Time Polymerase Chain Reaction , Retrospective Studies , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/virology , Uterine Cervicitis/metabolism , Uterine Cervicitis/microbiology , Vaginal Smears
17.
Nat Rev Urol ; 11(12): 672-87, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25330794

ABSTRACT

Sexually transmitted diseases (STDs) are caused by several pathogens, including bacteria, viruses and protozoa, and can induce male infertility through multiple pathophysiological mechanisms. Additionally, horizontal transmission of STD pathogens to sexual partners or vertical transmission to fetuses and neonates is possible. Chlamydia trachomatis, Ureaplasma spp., human papillomavirus, hepatitis B and hepatitis C viruses, HIV-1 and human cytomegalovirus have all been detected in semen from symptomatic and asymptomatic men with testicular, accessory gland and urethral infections. These pathogens are associated with poor sperm quality and decreased sperm concentration and motility. However, the effects of these STD agents on semen quality are unclear, as are the effects of herpes simplex virus type 1 and type 2, Neisseria gonorrhoeae, Mycoplasma spp., Treponema pallidum and Trichomonas vaginalis, because few studies have evaluated the influence of these pathogens on male infertility. Chronic or inadequately treated infections seem to be more relevant to infertility than acute infections are, although in many cases the exact aetiological agents remain unknown.


Subject(s)
Infertility, Male , Semen/microbiology , Semen/parasitology , Sexually Transmitted Diseases/complications , Chlamydia trachomatis , Cytomegalovirus , HIV , Hepacivirus , Hepatitis B virus , Humans , Infertility, Male/microbiology , Infertility, Male/parasitology , Male , Mycoplasma , Neisseria gonorrhoeae , Papillomaviridae , Semen/virology , Semen Analysis , Sexually Transmitted Diseases/microbiology , Sexually Transmitted Diseases/parasitology , Sexually Transmitted Diseases/transmission , Simplexvirus , Treponema pallidum , Trichomonas vaginalis , Ureaplasma
18.
Infect Agent Cancer ; 9(1): 6, 2014 Feb 11.
Article in English | MEDLINE | ID: mdl-24517499

ABSTRACT

BACKGROUND: Human Papillomavirus (HPV) infection is particularly burdensome for women infected with human immunodeficiency virus (HIV), which increases their risk of developing cervical lesions and cancer (CC). We conducted a molecular study of the distribution of cervical HPV genotypes and the risk factors for this infection in HIV-infected Brazilian women. FINDINGS: Cervical and endocervical samples for Papanicolaou screening and HPV detection were collected from 178 HIV-infected women using highly active antiretroviral therapy (HAART) of Maringá city/Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding to HIV infection from medical records. HPV was detected by polymerase chain reaction (PCR), and genotyping using PCR-restriction fragment length polymorphism analysis. HIV infection was well controlled, but women with a current CD4+ T lymphocyte count between 200-350 cells/mm3 (37.6%) had a two-fold greater risk of HPV infection than those with > 350 cells/mm3 (26.4%). HPV was associated with parity ≥3, hormonal contraceptive use and current smoker. HPV infection occurred with high frequency (46.6%) but a low frequency of cervical abnormalities was detected (7.30%), mainly low-grade squamous intraephitelial cervical lesions (LSIL) (84.6%). A high frequency of multiple HPV infections was detected (23.0%), and the most frequent HPV genotype was HPV-72 (6.7%), followed by -16, -31 and -51 (6.14% each). CONCLUSIONS: We showed that HAART use does not protect HIV-infected women from HPV, but appear to exert some protection against cervical lesions development. This study provides other important information about risk factors and cervical HPV in HIV-infected women, which can contribute to planning protocols.

19.
Am J Trop Med Hyg ; 89(6): 1199-202, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24080632

ABSTRACT

We determined the prevalence of seven clinically important pathogens that cause sexually transmitted infections (STIs) (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, herpes simplex virus 1 [HSV-1], HSV-2, and Treponema pallidum), by using a multiplex polymerase chain reaction (M-PCR) in samples from Brazilian woman infected with human immunodeficiency virus 1 (HIV-1) and uninfected Brazilian women (controls). The M-PCR assay identified all STIs tested for and surprisingly, occurred association between the control and STIs. This association was probably caused by excellent HIV infection control and regular monitoring in these women established by public health strategies in Brazil to combat HIV/acquired immunodeficiency syndrome. Studies using this M-PCR in different populations may help to better elucidate the roles of STIs in several conditions.


Subject(s)
HIV Infections/epidemiology , Multiplex Polymerase Chain Reaction/methods , Sexually Transmitted Diseases/diagnosis , Adult , Brazil/epidemiology , Chlamydia trachomatis/genetics , Chlamydia trachomatis/isolation & purification , DNA Primers/genetics , Female , HIV Infections/complications , Herpesvirus 1, Human/genetics , Herpesvirus 1, Human/isolation & purification , Herpesvirus 2, Human/genetics , Herpesvirus 2, Human/isolation & purification , Humans , Middle Aged , Mycoplasma genitalium/genetics , Mycoplasma genitalium/isolation & purification , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/isolation & purification , Prevalence , Sexually Transmitted Diseases/epidemiology , Treponema pallidum/genetics , Treponema pallidum/isolation & purification , Trichomonas vaginalis/genetics , Trichomonas vaginalis/isolation & purification
20.
BMC Complement Altern Med ; 13: 196, 2013 Jul 28.
Article in English | MEDLINE | ID: mdl-23890053

ABSTRACT

BACKGROUND: Sapindus saponaria is used traditionally for curing ulcers, external wounds and inflammations. The spermicidal and anti-Trichomonas activity of S. saponaria and its effect on Lactobacillus acidophilus were evaluated. METHODS: Water-ethanol (WE) and butanolic (BE) extracts, as well as a purified sample of saponins (SP) from S. saponaria were tested for spermicidal and anti-Trichomonas activity and for their effect on L. acidophilus. RESULTS: WE, BE and SP immobilized spermatozoa at a minimum effective concentration (MEC) of 2.5 (gram %) for extracts and 1.25 (gram %) for SP. The effective concentrations that caused 50% immobilization of spermatozoa (EC50) were 0.5 (gram %) for WE and SP, and 0.1 (gram %) for BE. The compounds were effective against Trichomonas vaginalis (Minimum Inhibitory Concentration = 0.156 mg/mL for WE and BE, and 0.078 mg/mL for SP against a clinical strain (CS); and 0.312, 0.156 and 0.078 mg/mL for WE, BE and SP, respectively, against an ATCC strain). In all concentrations tested, the growth of L. acidophilus was not reduced. CONCLUSION: The in vitro study proved the spermicidal and anti-Trichomonas activity of S. saponaria. Complementary in vivo studies should be made for establish the use as a vaginal spermicide, particularly in Brazil and Latin America.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antiprotozoal Agents/pharmacology , Plant Extracts/pharmacology , Sapindus/chemistry , Spermatocidal Agents/pharmacology , Trichomonas vaginalis/drug effects , Adult , Brazil , Drug Evaluation, Preclinical , Humans , Lactobacillus acidophilus/drug effects , Male , Microbial Sensitivity Tests , Parasitic Sensitivity Tests , Saponins/pharmacology , Spermatozoa/drug effects , Young Adult
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