Innate immunity and regulatory T-cells in human Chagas disease: what must be understood?

There is a general consensus that during chronic Trypanosoma cruzi infection, the host immune system induces complex processes to ensure the control of parasite growth while preserving the potential to mount and maintain a life-long controlled humoral and cellular immune response against the invading pathogen. This review summarises evidence in an attempt to elucidate "what must be understood" to further clarify the role of innate immunity in the development/maintenance of clinical Chagas disease and the impact of etiological treatment on host immunity, highlighting the contributions of the innate immunity and regulatory T (Treg) cells. Recently, increasing focus on innate immunity suggest that chronic T. cruzi infection may cause morbidity when innate effector functions, or the down-regulation of adaptive regulatory mechanisms are lacking. In this context, stable asymptomatic host-parasite interactions seem to be influenced by the effector/regulatory balance with the participation of macrophages, natural killer (NK) and CD8+ T cells in parallel with the establishment of regulatory mechanisms mediated by NKT and Treg cells. Moreover, a balanced innate immune activation state, apart from Treg cells, may play a role in controlling the adverse events triggered by the massive antigen release induced by trypanosomicidal agents during Chagas disease etiological treatment.

Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents)

This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

VISUAL ART AND REGULATORY FIT MESSAGES ON CONSUMER EVALUATIONS

ABSTRACT In this study, we demonstrate that the art infusion effect, in which the presence of visual art causes a positive impact on consumers' perceptions of products and advertising messages, might have a moderation effect on regulatory fit and non-fit messages. We investigate the impact of visual art on advertisement evaluations in regulatory (non-) fit conditions. Regulatory focus theory suggests that consumers rely on their motivational focus (prevention vs. promotion) for their evaluations and decisions. Usually, consumers prefer products that fit with their personal motivational focus. In the present study, the results of three experiments indicate that using visual art with a promotion or prevention fit message is recommended, while non-art images increase message persuasiveness when non-fit messages are presented. Therefore, not all information compatible with the consumer's motivational focus are best evaluated. When non-art images are presented, non-fit messages might be more persuasive.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

AbstractLatent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

The general practitioner and the surgeon: stereotypes and medical specialties

OBJECTIVE: To investigate and characterize the professional stereotypes associated with general medicine and surgery among Brazilian medical residents. METHODS: A randomized sample of residents of the General Medicine and Surgery Residence Programs were interviewed and their perceptions and views of general and surgical doctors were compared. RESULTS: The general practitioner was characterized by the residents in general to be principally a sensitive and concerned doctor with a close relationship with the patient; (45%); calm, tranquil, and balanced (27%); with intellectual skills (25%); meticulous and attentive to details (23%); slow to resolve problems and make decisions (22%); and working more with probabilities and hypotheses (20%). The surgeon was considered to be practical and objective (40%); quickly resolving problems (35%); technical with manual skills (23%); omnipotent, arrogant, and domineering (23%); anxious, stressed, nervous, and temperamental (23%); and more decided, secure, and courageous (20%). Only the residents of general medicine attributed the surgeon with less knowledge of medicine and only the surgeons attributed gender characteristics to their own specialty. CONCLUSION: There was considerable similarity in the description of a typical general practitioner and surgeon among the residents in general, regardless of the specialty they had chosen. It was interesting to observe that these stereotypes persist despite the transformations in the history of medicine, i.e. the first physicians (especially regarding the valorization of knowledge) and the first surgeons, so-called "barber surgeons" in Brazil (associated with less knowledge and the performance of high-risk procedures).

Identification and characterization of the two-component NtrY/NtrX regulatory system in Azospirillum brasilense

Two Azospirillum brasilense open reading frames (ORFs) exhibited homology with the two-component NtrY/NtrX regulatory system from Azorhizobium caulinodans. These A. brasilense ORFs, located downstream to the nifR3ntrBC operon, were isolated, sequenced and characterized. The present study suggests that ORF1 and ORF2 correspond to the A. brasilense ntrY and ntrX genes, respectively. The amino acid sequences of A. brasilense NtrY and NtrX proteins showed high similarity to sensor/kinase and regulatory proteins, respectively. Analysis of lacZ transcriptional fusions by the ß-galactosidase assay in Escherichia coli ntrC mutants showed that the NtrY/NtrX proteins failed to activate transcription of the nifA promoter of A. brasilense. The ntrYX operon complemented a nifR3ntrBC deletion mutant of A. brasilense for nitrate-dependent growth, suggesting a possible cross-talk between the NtrY/X and NtrB/C sensor/regulator pairs. Our data support the existence of another two-component regulatory system in A. brasilense, the NtrY/NtrX system, probably involved in the regulation of nitrate assimilation.

Association between tooth loss and obesity in Brazilian adults: a population-based study

OBJECTIVE: To examine the association between tooth loss and general and central obesity among adults. METHODS: Population-based cross-sectional study with 1,720 adults aged 20 to 59 years from Florianópolis, Southern Brazil. Home interviews were performed and anthropometric measures were taken. Information on sociodemographic data, self-reported diabetes, self-reported number of teeth, central obesity (waist circumference [WC] > 88 cm in women and > 102 cm in men) and general obesity (body mass index [BMI] ≥ 30 kg/m²) was collected. We used multivariable Poisson regression models to assess the association between general and central obesity and tooth loss after controlling for confounders. We also performed simple and multiple linear regressions by using BMI and WC as continuous variables. Interaction between age and tooth loss was also assessed. RESULTS: The mean BMI was 25.9 kg/m² (95%CI 25.6;26.2) in men and 25.4 kg/m2 (95%CI 25.0;25.7) in women. The mean WC was 79.3 cm (95%CI 78.4;80.1) in men and 88.4 cm (95%CI 87.6;89.2) in women. A positive association was found between the presence of less than 10 teeth in at least one arch and increased mean BMI and WC after adjusting for education level, self-reported diabetes, gender and monthly per capita income. However, this association was lost when the variable age was included in the model. The prevalence of general obesity was 50% higher in those with less than 10 teeth in at least one arch when compared with those with 10 or more teeth in both arches after adjusting for education level, self-reported diabetes and monthly per capita family income. However, the statistical significance was lost after controlling for age. CONCLUSIONS: Obesity was associated with number of teeth, though it depended on the participants' age groups.

Gender differences in the association between tooth loss and obesity among older adults in Brazil

OBJECTIVE To analyze if differences according to gender exists in the association between tooth loss and obesity among older adults.METHODS We analyzed data on 1,704 older adults (60 years and over) from the baseline of a prospective cohort study conducted in Florianopolis, SC, Southern Brazil. Multivariable logistic regression models were used to assess the association between tooth loss and general and central obesity after adjustment for confounders (age, gender, skin color, educational attainment, income, smoking, physical activity, use of dentures, hypertension, and diabetes). Linear regressions were also assessed with body mass index and waist circumference as continuous outcomes. Interaction between gender and tooth loss was further assessed.RESULTS Overall mean body mass index was 28.0 kg/m2. Mean waist circumference was 96.8 cm for males and 92.6 cm for females. Increasing tooth loss was positively associated with increased body mass index and waist circumference after adjustment for confounders. Edentates had 1.4 (95%CI 1.1;1.9) times higher odds of being centrally obese than individuals with a higher number of teeth; however, the association lost significance after adjustment for confounders. In comparison with edentate males, edentate females presented a twofold higher adjusted prevalence of general and central obesity. In the joint effects model, edentate females had a 3.8 (95%CI 2.2;6.6) times higher odds to be centrally obese in comparison with males with more than 10 teeth present in both the arches. Similarly, females with less than 10 teeth in at least one arch had a 2.7 (95%CI 1.6;4.4) times higher odds ratio of having central obesity in comparison with males with more than 10 teeth present in both the arches.CONCLUSIONS Central obesity was more prevalent than general obesity among the older adults. We did not observe any association between general obesity and tooth loss. The association between central obesity and tooth loss depends on gender – females with tooth loss had greater probability of being obese.

Infection by Trypanosoma cruzi in mammals in Yucatan, Mexico: a serological and parasitological study

In order to determine Trypanosoma cruzi infection among mammals in Yucatan, Mexico, 372 animals, both wild and synanthropic including carnivores, marsupials and rodents were studied. Serological studies by indirect haemagglutination (IHA) were carried out to detect antibodies to T. cruzi and a parasitological study was also performed (blood smear and histopathology). Of all the animals tested 18.54% were serologically positive, with a significantly higher frequency among the wild ones (33.33%) compared to the synanthropic ones (17.79%). To determine T. cruzi in positive animals, blood was inoculated into a white mouse (webster type) to prove myocardium colonization. The serological and parasitological positivity of these animals, as well as their behavior in the environment, taken together with the socioeconomic and cultural characteristics of the population, suggest that in Yucatan, Mexico, Canis familiaris, Didelphis marsupialis and Rattus rattus act as a link with the wild cycle.

Kinetics of IFN-gamma, TNF-alpha, IL-10 and IL-4 production by mononuclear cells stimulated with gp43 peptides, in patients cured of paracoccidioidomycosis

We analyzed the kinetics of cytokine production by mononuclear cells from 17 patients who had been treated for paracoccidioidomycosis, using the stimulus of gp43 peptide groups (43kDa glycoprotein of Paracoccidioides brasiliensis) at 0.1 and 1µM, gp43 (1µg/ml) and crude Paracoccidioides brasiliensis antigen (PbAg; 75µg/ml). IFN-gamma production was a maximum at 144 hours in relation to the G2 and G8 peptide groups at 1µM and was greatest at 144 hours when stimulated by gp43 and by PbAg. The maximum TNF-alpha production was at 144 hours for the G2 group (0.1µM) and for gp43. IL-10 production was highest after 48 and 72 hours for G7 and G6 at 1µM, respectively. We also suggest the best time for analysis of IL4 production. These results may contribute towards future studies with gp43 peptides and encourage further investigations with the aim of understanding the influence of these peptides on the production of inflammatory and regulatory cytokines.

Effects of an exercise program on blood pressure in patients with treated hypertension and chronic Chagas' heart disease

INTRODUCTION: Previous studies describe an imbalance of the autonomic nervous system in Chagas' disease causing increased sympathetic activity, which could influence the genesis of hypertension. However, patients undergoing regular physical exercise could counteract this condition, considering that exercise causes physiological responses through autonomic and hemodynamic changes that positively affect the cardiovascular system. This study aimed to evaluate the effects of an exercise program on blood pressure in hypertensive patients with chronic Chagas' heart disease. METHODS: We recruited 17 patients to a 24-week regular exercise program and used ambulatory blood pressure monitoring before and after training. We determined the differences in the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) from the beginning to the end of the study. RESULTS: The blood pressures were evaluated in general and during periods of wakefulness and sleep, respectively: SBP (p = 0.34; 0.23; 0.85), DBP (p = 0.46; 0.44; 0.94) and MBP (p = 0.41; 0.30; 0.97). CONCLUSIONS: There was no statistically significant change in blood pressure after the 24-week exercise program; however, we concluded that physical training is safe for patients with chronic Chagas' disease, with no incidence of increase in blood pressure.

Trans-cultural aspects of social anxiety disorder and related conditions: a Brazilian case series and a review of international clinical studies

Cross-cultural studies have much to teach clinicians and researchers alike about psychopathology in general and about social anxiety disorder (SAD) in particular. Unfortunately, little is known about the degree and the mechanisms through which cultural environment may influence clinical manifestations of SAD. OBJECTIVE: Our objective was to identify culture-related clinical patterns in SAD and related disorders. METHODS: We described socio-demographic and clinical characteristics of a sample of 62 adult outpatients with SAD seen at a university clinic for anxiety and depressive disorders in Rio de Janeiro, Brazil, and compared them with those reported in clinical samples from North America, Europe, Asia and Oceania identified through a systematic review in Medline, PsychINFO, and LILACS. RESULTS: Our comparison of trans-cultural features of SAD lends partial support to Heimberg's (1997) contention that the majority of socio-demographic features and symptoms of this disorder are relatively independent of geographic and cultural differences. CONCLUSION: Patients with SAD were almost universally characterized by: 1) a predominance of males in clinical samples; 2) early onset of the disorder; 3) high educational attainment; and 4) great frequency of comorbidities.

The influence of shell species and size on the shell selection pattern of Paguristes tortugae (Decapoda, Diogenidae) from Anchieta Island (Ubatuba, Brazil)

Shell selection by the hermit crab Paguristes tortugae Schmitt, 1933 from Anchieta Island (Brazil) was analyzed using the six most frequently occupied shell species in the field and taking into account the sexual condition of the individuals, the shell size and the shell species. The experiments were conducted under laboratory conditions and the shell species preference was estimated on the basis of the frequency that each species was chosen by the individuals. The preferred shell species and size were determined by regression analysis. The highest correlation coefficients were obtained for the relations between the hermit dimensions and shell dry weight. The ovigerous females preferred shells with larger internal volume: Leucozonia nassa (Gmelin, 1791) and Cerithium atratum (Born, 1778). In the experiment of shell size, males preferred heavier shells whereas females selected the shape characteristics of the shell, such as the aperture and the internal volume, which are probably related to the growth and offspring guarantee, respectively. In general, and independent of sex condition, P. tortugae showed significant selection among all shells utilized. The results suggest that shell selection by P. tortugae involves sexual and reproductive condition preferences.

Effects of precocene and azadirachtin in Rhodnius prolixus: some data on development and reproduction

The results presented in this paper clearly indicate that precocene and azadirachtin are effective inhibitors of moulting and reproduction in the hemipteran Rhodnius prolixus. The time of application is important and only applications of these substances early in the intermoulting period cause their effects in nymphs. The inhibition of moulting is fully reversed by ecdysone therapy. Precocene and azadirachtin also affected drastically the oogenesis and egg deposition in this insect. Precocene-induced sterilization is reversed by application of juvenile hormone III. However, this hormone is unable to reverse the effect of azadirachtin on reproduction. Ecdysteroid titers in nymphs and adult females are decreased by these treatments. In vitro analysis suggest that precocene and azadirachtin may act directly on the prothoracic glands and ovaries producing ecdysteroids. Based on these and other findings the possible mode of action of these compounds on the development and reproduction of Rhodnius prolixus is discussed.