Brazilian red propolis exerts a cytotoxic action against prostate cancer cells and upregulates human monocyte functions.

Different propolis samples can be obtained in Brazil, such as green, brown and red. Studies related to Brazilian red propolis (BRP) have increased in the last few years, so the aim of this study was to investigate its effects on the prostate cell lines LNCaP and PC-3 and on human monocytes. BRP chemical composition was analyzed by HPLC-DAD, the viability of monocyte and cancer cell by MTT assay. Cytokine production (TNF-α, IL-1ß, IL-6, IL-10) by monocytes was quantitated by ELISA, the expression of cell markers (TLR-2, TLR-4, HLA-DR, CD80) and reactive oxygen species by flow cytometry. The candidacidal activity and the effects of supernatant of treated monocytes on tumor cells were assessed. BRP affected LNCaP viability after 48 and 72 h, while PC-3 cells were more resistant over time. BRP upregulated CD80 and HLA-DR expression, and stimulated TNF-α, IL-6 and IL-10 production. BRP enhanced the fungicidal activity of monocytes, displayed an antioxidant action and the supernatant of BRP-treated monocytes diminished LNCaP viability. In the search for new immunomodulatory and antitumoral agents, BRP exerted a selective cytotoxic activity on prostate cancer cells and an immunomodulatory action, suggesting its potential for clinical trials with oncological patients and for the discovery of new immunomodulatory and antitumor drugs.

Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF-7 breast cancer cells and on women monocyte.

Docetaxel (DTX) is used against breast cancer despite its side effects such as toxicity and immunosuppression. Here we investigated the cytotoxic and immunomodulatory effects of the ethanol solution extract of propolis (EEP) in combination with DTX on MCF-7 breast cancer cells and on women's monocyte. The cytotoxic potential of EEP + DTX was assessed by MTT assay and the type of tumor cell death was evaluated by flow cytometry. The effects of EEP + DTX on the migration and invasion of MCF-7 cells were analyzed. Cytokine production by monocytes was assessed by ELISA and the expression of cell surface markers was evaluated by flow cytometry. We also assessed the fungicidal activity of monocytes against Candida albicans and the generation of reactive oxygen species (ROS). Finally, the impact of the supernatants of treated monocytes in the viability, migration, and invasiveness of tumor cells was assessed. EEP enhanced the cytotoxicity of DTX alone against MCF-7 cells by inducing necrosis and inhibiting their migratory ability. EEP + DTX exerted no cytotoxic effects on monocytes and stimulated HLA-DR expression, TNF-α, and IL-6 production, exerted an immunorestorative action in the fungicidal activity, and reduced the oxidative stress. Our findings have practical implications and reveal new insights for complementary medicine.

Contributory role of ART in the development of non-AIDS comorbidities in asymptomatic PLWHA.

BACKGROUND: Despite the many benefits that follow antiretroviral therapy (ART) initiation, its chronic use contributes to the early aging of people living with HIV/AIDS (PLWHA). The aim of this cross-sectional study was to trace the prevalence of and investigate possible renal, bone and metabolic changes, as well as cardiovascular risk in 94 asymptomatic PLWHA, relating them to the duration of ART use. METHODS: Four groups were evaluated according to ART use: G1 (n = 21), ART-naïve individuals; G2 (n = 17), <2 years; G3 (n = 40), 2-10 years; and G4 (n = 16) on ART for more than 10 years. RESULTS: Our results showed a high prevalence of dyslipidemic individuals (64%), especially in those under ART. Lower creatine phosphokinase levels were observed in G1 as compared to the others (p < 0.05). Regarding the Framingham score, 12.1% of PLWHA showed moderate and high risk, and the highest proportion (38.5%) occurred in G4 (p = 0.003). A decrease in glomerular filtration rates occurred in 20% of patients, which was also more significant in G3 and G4 (p = 0.007). High prevalences of osteopenia and osteoporosis (53.2%) were found, especially in G1 and G4; however, G1 showed the lowest means for alkaline phosphatases (AP, p = 0.04 and BAP, p = 0.005) and osteocalcin (p = 0.005), in addition to higher vitamin-D concentrations (p = 0.04). CONCLUSIONS: Our study showed the possible contributory role of ART in these changes, which leads us to reflect on the need for specific conducts and patient care, pointing out the importance of individualized care in an attempt to increase life expectancy.

The Initial Months of Antiretroviral Therapy and Its Influence on AGEs, HMGB1, and sRAGE Levels in Asymptomatic HIV-Infected Individuals.

The development of the typical comorbidities of aging which currently affects people living with HIV/AIDS (PLWHA) can be partially ascribed to the persistent immune activation and chronic inflammation characterizing these individuals. The aim of this study was to analyze the effect exerted by combined antiretroviral therapy (cART) administration on plasma levels of HMGB1 (high mobility group box protein-1), AGEs (advanced glycation end products), their soluble receptor sRAGE, cytokines, C-reactive protein (CRP), and some metabolic markers in asymptomatic PLWHA. Analyses were performed longitudinally in 30 PLWHA, before and about 6-12 months after cART initiation. We observed that lower levels of AGEs in post-cART group were accompanied by an increase of CRP and triglyceride levels already in the early months of therapy. Because of the current ever-earlier recommendations to start cART and its prolonged use, these and other markers should be investigated in order to monitor and postpone the appearance of non-AIDS comorbidities in PLWHA.

Saliva as a Biological Fluid in SARS-CoV-2 Detection.

BACKGROUND: The polymerase chain reaction of upper respiratory tract swab samples was established as the gold standard procedure for diagnosing SARS-CoV-2 during the COVID pandemic. However, saliva collection has attracted attention as an alternative diagnostic collection method. The goal of this study was to compare the use of saliva and nasopharyngeal swab (NPS) samples for the detection of SARS-CoV-2. METHODS: Ninety-nine paired samples were evaluated for the detection of SARS-CoV-2 by saliva and swab for a qualitative diagnosis and quantitative comparison of viral particles. Furthermore, the detection limits for each sample collection technique were determined. The cycle threshold (CT) values of the saliva samples, the vaccination status, and the financial costs associated with each collection technique were compared. RESULTS: The results showed qualitative equivalence in diagnosis (96.96%) comparing saliva and swab collection, although there was low quantitative agreement. Furthermore, the detection limit test demonstrated equivalence for both collection methods. We did not observe a statistically significant association between CT values and vaccination status, indicating that the vaccine had no influence on viral load at diagnosis. Finally, we observed that the use of saliva incurs lower financial costs and requires less use of plastic materials, making it more sustainable. CONCLUSIONS: These findings support the adoption of saliva collection as a feasible and sustainable alternative to the diagnosis of COVID-19.

Dichotomous outcomes vs. survival regression models for identification of predictors of mortality among patients with severe acute respiratory illness during COVID-19 pandemics.

Introduction: As the studies predicting mortality in severe acute respiratory illness (SARI) have inferred associations either from dichotomous outcomes or from time-event models, we identified some clinical-epidemiological characteristics and predictors of mortality by comparing and discussing two multivariate models. Methods: To identify factors associated with death among all SARI hospitalizations occurred in Botucatu (Brazil)/regardless of the infectious agent, and among the COVID-19 subgroup, from March 2020 to 2022, we used a multivariate Poisson regression model with binomial outcomes and Cox proportional hazards (time-event). The performance metrics of both models were also analyzed. Results: A total of 3,995 hospitalized subjects were included, of whom 1338 (33%) tested positive for SARS-CoV-2. We identified 866 deaths, of which 371 (43%) were due to the COVID-19. In the total number of SARI cases, using both Poisson and Cox models, the predictors of mortality were the presence of neurological diseases, immunosuppression, obesity, older age, and need for invasive ventilation support. However, the Poisson test also revealed that admission to an intensive care unit and the COVID-19 diagnosis were predictors of mortality, with the female gender having a protective effect against death. Likewise, Poisson proved to be more sensitive and specific, and indeed the most suitable model for analyzing risk factors for death in patients with SARI/COVID-19. Conclusion: Given these results and the acute course of SARI and COVID-19, to compare the associations and their different meanings is essential and, therefore, models with dichotomous outcomes are more appropriate than time-to-event/survival approaches.

Propolis anti-inflammatory effects on MAGE-1 and retinoic acid-treated dendritic cells and on Th1 and T regulatory cells.

Background: Propolis exhibits huge potential in the pharmaceutical industry. In the present study, its effects were investigated on dendritic cells (DCs) stimulated with a tumor antigen (MAGE-1) and retinoic acid (RA) and on T lymphocytes to observe a possible differential activation of T lymphocytes, driving preferentially to Th1 or Treg cells. Methods: Cell viability, lymphocyte proliferation, gene expression (T-bet and FoxP3), and cytokine production by DCs (TNF-α, IL-10, IL-6 and IL-1ß) and lymphocytes (IFN-γ and TGF-ß) were analyzed. Results: MAGE-1 and RA alone or in combination with propolis inhibited TNF-α production and induced a higher lymphoproliferation compared to control, while MAGE-1 + propolis induced IL-6 production. Propolis in combination with RA induced FoxP3 expression. MAGE-1 induced IFN-γ production while propolis inhibited it, returning to basal levels. RA inhibited TGF-ß production, what was counteracted by propolis. Conclusion: Propolis affected immunological parameters inhibiting pro-inflammatory cytokines and favoring the regulatory profile, opening perspectives for the control of inflammatory conditions.

Oxidative stress evaluation in patients with chronic Chagas disease.

INTRODUCTION: Chagas disease (CD), caused by protozoan Trypanosoma cruzi (T. cruzi), is a neglected disease that affects millions of people worldwide. The parasite clearance by the immune cells is accomplished by the activation of inflammation and production of reactive oxygen species, including nitric oxide (NO) that can lead to tissue injury and DNA damage. On the other hand, to balance the oxidative environment and decrease free radicals, there is an antioxidant system composed of enzymes and vitamins. The aim was to evaluate oxidative stress parameters in symptomatic and asymptomatic patients with Chagas disease. METHODS: Participants were divided into three groups: indeterminate CD (asymptomatic, n = 8), CD with cardiac/digestive involvement (symptomatic, n = 14), and Control healthy individuals (n = 20). The following parameters were analyzed: DNA damage, NO serum levels, hydrophilic antioxidant capacity (HAC) and vitamin E. RESULTS: Symptomatic patients showed increased DNA damage and NO levels and lower HAC and vitamin E levels compared to asymptomatic patients and control subjects. CONCLUSIONS: It is possible to conclude that CD patients with clinical symptoms have higher oxidative stress, characterized by increased DNA damage and NO levels, and reduced antioxidant capacity and vitamin E levels.

Propolis consumption by asymptomatic HIV-individuals: Better redox state? A prospective, randomized, double-blind, placebo-controlled trial.

Propolis is a natural product has many biological properties of clinical interest, such as anti-inflammatory and antioxidant. Considering that people living with HIV/aids (PLWHA) on effective combined antiretroviral therapy (cART) present early aging due to an intense immune activation, inflammation, and redox imbalance, propolis consumption could offer a benefit to such patients. This double-blind longitudinal study evaluated whether Brazilian green propolis pills intake (500 mg/day for three months) would decrease the oxidative stress of virological suppressed HIV-individuals. To compare each group (propolis, n = 20 versus placebo, n = 20) in both moments (M0, before and M1, after the intervention), the following markers were assessed: plasma malondialdehyde (MDA), carbonylation, total oxide nitric, total antioxidant capacity (TAP), superoxide dismutase, catalase, and NFkB and NRF2 gene expression. Data were analyzed using Poisson, Gamma distribution and ANOVA followed by Tukey-Kramer. The groups were homogeneous regarding age, gender, time of diagnosis/ treatment, cART scheme, CD4+ T cell count, and no changes were observed in the diet food, or patients' lifestyles. A decreased MDA concentration was seen in the propolis group (M0 = 0.24 ± 0.13, M1 = 0.20 ± 0.10 protein nmol/mg; p = 0.005) as well as a slight but non-significant increase of TAP (M0 = 49.07 ± 13.26, M1 = 52.27 ± 14.86%; p = 0.06). One may conclude that propolis promoted a lower lipid peroxidation and improved the antioxidant system, suggesting that its use may be beneficial to PLWHA in an attempt to contain the intense inflammatory and oxidant activity.

Safety of the Fiocruz ChAdOx COVID-19 vaccine used in a mass vaccination campaign in Botucatu, Brazil.

INTRODUCTION: Brazil has been at the core of the COVID-19 pandemic, with the second-highest death toll worldwide. A mass vaccination campaign was initiated on May 16th, 2021, in Botucatu, Brazil, where two doses of ChadOx1-nCoV19 were offered 12 weeks apart to all 18-60- year-olds. This context offers a unique opportunity to study the vaccine safety during a mass campaign. METHODS: The first and second doses of the vaccine were administered in May and August 2021, respectively. Emergency room (ER) and hospitalization records were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu for six weeks before and six weeks after the first and second doses, from 4 April to 19 September 2021. Diagnoses with COVID-19-related ICD codes were excluded to distinguish any trends resulting from the COVID-19 pandemic. ER and hospital visits during the two time periods were compared, including an ICD code comparison, to identify any changes in disease distributions. Data were scanned for a defined list of Adverse Events of Special Interest (AESIs), as presented by the Safety Platform for Emergency Vaccines. RESULTS AND DISCUSSION: A total of 77,683 and 74,051 subjects received dose 1 and dose 2 of ChadOx1-nCoV19, respectively. Vaccination was well tolerated and not associated with any major safety concerns. Increases in ER visits 1 week following both doses were primarily seen in ICD codes related to non-serious side effects of the vaccine, including vaccination site pain and other local events. The neurological AESIs identified (2 of 3 cases of multiple sclerosis) were relapses of a pre-existing condition. One potentially serious hospitalization event for Bell's palsy had onset before vaccination with dose 1, in a patient who also had a viral infection of the central nervous system. There was no myocarditis, pericarditis cases, or vaccine-related increases in thromboembolic events.

Effectiveness of the Fiocruz recombinant ChadOx1-nCoV19 against variants of SARS-CoV-2 in the Municipality of Botucatu-SP.

Introduction: As the COVID-19 pandemic progresses, rapidly emerging variants of concern raise fears that currently licensed vaccines may have reduced effectiveness against these new strains. In the municipality of Botucatu, São Paulo State, Brazil, a mass vaccination campaign using ChadOx1-nCoV19 was initiated on 16th of May 2021, targeting people 18-60 years old. Two vaccine doses were offered 12 weeks apart, with the second delivered on 8th of August, 2021. This setting offered a unique opportunity to assess the effectiveness of two ChadOx1-nCoV19 doses in a real-life setting. Materials and methods: Data on testing, hospitalization, symptoms, demographics, and vaccination were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu. A test-negative study design was employed; whereby the odds of being vaccinated among cases vs controls were calculated to estimate vaccine effectiveness (VE; 1-OR). All individuals aged 18-60 who received a PCR test after the 16th of May and were unvaccinated prior to this date were included in the analysis until the study ended in mid-November 2021. Results: 77,683 citizens of Botucatu aged 18-60 received the first dose, and 74,051 received a second ChadOx1-nCoV19 dose 12 weeks later for a vaccination coverage of 84.2 and 80.2%, respectively. Of 7.958 eligible PCR tests, 2.109 were positive and 5.849 negative. The VE against any symptomatic infection was estimated at 39.2%, 21 days after dose 1, and 74.5%, 14 days after dose 2. There were no COVID-19-related hospitalizations or deaths among the 74,051 fully vaccinated individuals. The VE against severe disease was estimated at 70.8 and 100% after doses 1 and 2, respectively. 90.5% of all lineages sequenced between doses 1 and 2 (16th of May-7th of August) were of the Gamma variant, while 83.0% were of the Delta variant during the second period after dose 2 (8th of August-18th of November). Discussion: This observational study found the effectiveness of ChadOx1-nCoV19 to be 74.5% against COVID-19 disease of any severity, comparable to the efficacy observed in clinical trials (81.3% after dose 2), despite the dominance of the Gamma and Delta VoCs. No COVID-19-related hospitalizations or deaths in fully vaccinated individuals were reported.

Visceral leishmaniasis in a captive crab-eating fox Cerdocyon thous.

Visceral leishmaniasis (VL) is a zoonotic disease with worldwide distribution. The crab-eating fox (Cerdocyon thous) is considered a wild reservoir of many zoonotical diseases, particularly VL. This study reported the presence of Leishmania infantum amastigotes in different organs of one captive C. thous found dead in a zoo. This animal was positive by the indirect fluorescence antibody test and had many clinical signs of VL. Intracellular amastigote forms of L. infantum were seen in neutrophils and macrophages in sample tissues from skin, lymph nodes (popliteal, submandibular, prescapular, and mesenteric), spleen, and liver. The numbers of positive cells and intracellular parasites were higher in macrophages than in neutrophils. In addition, polymerase chain reaction demonstrated extensive distribution of Leishmania DNA in C. thous tissues from multiple organs. The presence of intracellular amastigotes in neutrophils and macrophages as well as DNA of the parasite in tissues, specifically skin demonstrate that this crab-eating fox is an adequate host for L. infantum and reinforce the importance of VL for symptomatic wild canids kept in captivity in endemic areas.

Redox imbalance is related to HIV and pregnancy.

Redox imbalance may compromise the homeostasis of physiological processes indispensable to gestational development in HIV-infected women. The present study aims to evaluate markers of the redox system in the development of pregnancy of these women. HIV-positive pregnant women, HIV-negative pregnant women and non-pregnant were studied. Redox markers superoxide dismutase (SOD), catalase (CAT), protein carbonylation and malondialdehyde (MDA) were assessed at first or second trimester, third trimester and postpartum from pregnant and from non-pregnant women. According to the longitudinal analysis model, CAT activity was increased in the postpartum in HIV-positive women and before delivery in HIV-negative women. Increased carbonylation was observed in the pre-delivery period of HIV-negative pregnant women and MDA concentrations were higher in HIV-positive pregnant women compared to those non-infected by HIV at all times. According to the factorial model, higher SOD and CAT activities were observed in HIV-positive women in the initial months of pregnancy and in non-pregnant women. Carbonylation at third trimester was more evident in HIV-negative pregnant women. MDA levels were higher in HIV-positive pregnant women. Increased oxidative stress may occur in HIV-infected pregnant women. Nevertheless, the HIV virus is not solely responsible for this process; instead, mechanisms inherent to the pregnancy seem to play a role in this imbalance.

Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment.

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.

Propolis increases Foxp3 expression and lymphocyte proliferation in HIV-infected people: A randomized, double blind, parallel-group and placebo-controlled study.

HIV infection and the prolonged use of antiretroviral therapy (ART) contribute to persistent inflammation and immune deregulation in people living with HIV/AIDS (PLWHA). Propolis is a bee product with plenty of biological properties, including immunomodulatory and anti-inflammatory action. This work aimed to evaluate possible changes in the immune/inflammatory response in PLWHA under ART after propolis intake. Asymptomatic PLWHA were double-blindly randomized into parallel groups receiving propolis (500 mg/day, n = 20) for 3 months or placebo (n = 20). Plasma cytokines (TNF-α, IL-2, IL-4, IL-6, IL-10 and IL17) were evaluated by cytometric bead array; cytokine production by PBMC (IFN-γ, IL-5, IL-17, IL-10, IL-1ß, IL-18, and IL-33) was assessed by ELISA; gene expression (T-bet, GATA-3, RORγt and Foxp3) was determined by RT-qPCR, and cell proliferation was analysed by flow cytometry using CFSE staining. The average of gender, age, CD4+/CD8+ T cell count, time of diagnosis and treatment were similar in both groups. No differences were observed in cytokine levels nor in inflammasome activation. However, Pearson's correlation showed that IL-10 was directly correlated to CD4+ T cell count and inversely to IFN-γ after treatment with propolis. Foxp3 expression and lymphocyte proliferation increased in the propolis group. Data suggested that daily propolis consumption may improve the immune response and decrease the inflammatory status in asymptomatic PLWHA under ART.

Asymptomatic HIV People Present Different Profiles of sCD14, sRAGE, DNA Damage, and Vitamins, according to the Use of cART and CD4+ T Cell Restoration.

We aimed to analyze markers of immune activation, inflammation, and oxidative stress in 92 asymptomatic HIV-infected patients according to the adequate (AR, >500 cells/mm3) or inadequate (IR, <500 cells/mm3) CD4+ T recovery and the presence or absence of antiretroviral treatment (cART). In relation to those newly diagnosed, they were divided into two groups, cART-naïve IR (nIR) and cART-naïve AR (nAR). Among those diagnosed more than five years ago, the following division was made: the cART-naïve long-term nonprogressors (LTNP); patient under cART and AR (tAR); and patients under cART and IR (tIR). We investigated the expression of soluble receptor for advanced glycation end products (sRAGE), high-mobility group-box protein -1 (HMGB1), soluble CD14 (sCD14), IL-8, IL-10, 8-isoprostane, vitamins, and DNA damage. We observed higher levels of sRAGE in tAR as compared to nIR, nAR, LTNP, and more sCD14 than in nIR and nAR. As for IL-10 levels, we found nIR > nAR > LTNP > tAR > tIR. Higher levels of 8-isoprostane were observed in nIR. LTNP presented a higher retinol dosage than tAR and less genotoxic damage induced by oxidative stress than the other groups. We suggest that the therapy, despite being related to lesser immune activation and inflammation, alters the vitamin profile and consequently increases the oxidative stress of patients. In addition, the lowest genotoxic index for LTNP indicates that both VL and cART could be responsible for the increased DNA damage. More studies are needed to understand the influence of cART on persistent immune activation and inflammation.

Asymptomatic HIV-Infected Patients Present Blood Parameters Changed, According to Use of Therapy and the CD4+ T Cells Count

Abstract In HIV-patients, the imbalance in immunological, hematological and biochemical factors can contribute to the progression to AIDS and non-AIDS comorbidities, even during combined antiretroviral therapy (cART). In this cross-sectional study, we aimed to analyze some of these parameters in 138 different asymptomatic HIV-infected patients, doing multiple comparisons between the groups, which are dichotomized in the presence / absence of cART and type of immune response (immunological responders [iR,>500cells/mL] or non-responders [iNR,<500cells/ mL]). Were analyzed cytokines and other routine laboratory parameters. Our results showed high creatine phosphokinase and low IL-10 levels in cART-patients. They also presented metabolic alterations, including elevations in total cholesterol and triglycerides, particularly in those iNR. In ART-iR an increased alanine aminotransferase was observed. Those NAÏVE-iNR presented high LDL-cholesterol, C-reactive protein and lactate dehydrogenase values. The long-term non-progressors (LTNP) showed the best laboratory results. In conclusion, many blood parameters were changed in HIV-patients, especially in those under cART. To identify LTNP individuals could be important to discussions their early therapeutic onset.

Antiretroviral Therapy Initiation Alters the Redox System of Asymptomatic HIV-Infected Individuals: A Longitudinal Study.

Background. The combination antiretroviral therapy (cART) increases the oxidative stress in HIV-infected people, which in turn favors the onset and aggravation of non-AIDS comorbidities, a common situation affecting these individuals. We aimed to evaluate the influence of cART initiation on oxidative stress parameters. This is a longitudinal study including 30 asymptomatic patients divided according to their CD4+ T cell count (G1: <500 cell/mL; G2: >500 cell/mL) before (M0) and after (M1) cART initiation. We analyzed total antioxidant capacity (TAC), fat-soluble vitamins, malondialdehyde, 8-isoprostane, and DNA damage. Results. Results showed a decrease in TAC, retinol, α-tocopherol, and some carotenoids, in addition to a significant increase in DNA damage at M1. These changes were more evident in G2 subjects. Moreover, there was a significant 8-isoprostane increase at M1 in individuals belonging to G1. Conclusion. The results indicate that cART interfered in the redox system, mainly by reducing the antioxidant defenses. In addition, patients who had CD4+ T counts higher than 500 cells/mm3 showed more susceptibility to genotoxicity, while patients with less CD4+ T counts displayed more damage triggered by lipoperoxidation. Considering the early beginning of cART, its chronic use, and its capacity to alter the redox status, further long-term studies on larger cohorts are needed to define the best time to initiate therapy and to investigate new strategies to delay the development of non-AIDS diseases.

The involvement of TLR2 and TLR4 in cytokine and nitric oxide production in visceral leishmaniasis patients before and after treatment with anti-leishmanial drugs.

Toll-like receptors (TLRs) have significant involvement in Leishmania infection, although little is known about the relationship between these receptors, cytokines and nitric oxide (NO) in patients with visceral leishmaniasis (VL) before or after treatment with anti-leishmanial drugs. The goal of this study was to evaluate the expression of TLR2 and TLR4 in CD3+ and CD14+ cells and the production of TNF-α, IFN-γ, IL-17, IL-10, TGF-ß and NO in peripheral blood mononuclear cells (PBMCs) from VL patients pre- and post-treatment with anti-leishmanial drugs. In addition, we investigated whether these receptors were involved in the production of these cytokines and NO. In the active VL patients, increased TLR2 and TLR4 expression in lymphocytes and monocytes, increased production of TNF-α, IL-10 and TGF-ß and decreased production of IFN-γ, IL-17 and NO were observed. After treatment, TLR2 and TLR4 were still expressed in lymphocytes and monocytes, the TNF-α and IL-10 levels were lower, the production of IFN-γ, IL-17 and NO was higher, and the TGF-ß level remained high. Before treatment, the production of TNF-α and NO was associated with TLR2 and TLR4 expression, while IL-10 production was only associated with TLR2 expression. After treatment, both receptors were associated with the production of TNF-α, IFN-γ, IL-10 and NO, while the production of IL-17 was associated only with TLR4 expression. The results presented in this study suggest that both TLR2 and TLR4 participate in the modulation of cytokine and NO production in VL patients, contributing to the pathogenesis of VL prior to treatment and the protective immune response after treatment.

Prevalence of Anogenital Warts in Men with HIV/AIDS and Associated Factors.

BACKGROUND: Infection with human papilloma virus (HPV) is the most common sexually transmitted disease in the world. Among the 630 million new cases of HPV that occur each year, 30 million develop anogenital warts. Although subclinical infection with HPV is the most common cause, genital warts are also associated with immunosuppression caused by HIV. In view of the high prevalence of HPV/HIV co-infection particularly among men who have sex with men, the objectives of this study were to determine the prevalence of anogenital warts in men with HIV/AIDS and to identify associated factors. METHODS: A cross-sectional study was conducted on 159 men with HIV/AIDS consecutively selected at a referral service in Botucatu, São Paulo, Brazil, in which the association between sociodemographic, behavioral and clinical variables and the presence of anogenital warts was evaluated. After hierarchical analysis of the data, variables presenting a p value ≤ 0.2 were entered into an unconditional multivariate logistic regression model. RESULTS: Forty-nine (31%) of the HIV-positive patients had anogenital warts. The mean age was 44.6 ± 9.6 years. The main factors associated with the presence of anogenital warts were irregular antiretroviral treatment and genital herpes(HSV). CONCLUSION: The present study demonstrate that anogenital warts occur in almost one-third of the male population infected with HIV and factors associated with a higher risk of being diagnosed with anogenital warts were irregular cART use and co-infection with HSV, other variables could not be associated.