Testosterone leads to Trypanosoma cruzi glycoprotein synthesis and increased of inflammatory mediators in bone marrow-derived macrophages.

Despite all the scientific progress in recent decades to unravel the immune processes and the way the parasite bypasses the immune system, Chagas disease is still a major public health problem, affecting an estimated 3.5 million people. Among the components that may participate in the response against the parasite, testosterone has been gaining more and more visibility. Studies indicate that the parasite itself seems to carry out steroidogenesis, in which, in co-culture with androgen precursors, T. cruzi has been shown to produce TS, but the purpose of the TS synthesized by the parasite and how this can influence its invasion glycoproteins is still unclear unknown. The aim of this study was to evaluate the influence of testosterone in Trypanosoma cruzi infection on the immune response of bone marrow-derived macrophages. Bone marrow from male rats was extracted and cultured with RMPI medium containing 30% L929 cell supernatant for macrophage differentiation. The cells were incubated for 10 days and, after this period, they were seeded in 96 wells in the amount of 1 x 105 cells per well. TS was added at different concentrations of 20 µM, 10 µM, 5 µM and 1 µM and then infected with the Y strain of T. cruzi, at a rate of 10 parasites per cell, with the culture remaining for six, 12 and 24 h. The supernatant was collected and the production of nitric oxide (NO), tumor necrosis factor (TNF) and the number of cell parasites was assessed by staining with 4'-6'-diamino-2-phenylindole (DAPI) and ranked by high Content Screening (HSC). The parasite was then cultured with the addition of TS, at the mentioned concentrations, leaving it for six and 12 h and then performing the RT-PCR of the mucins. DAPI staining revealed a significant increase in the number of parasites in cells containing TS. The exception was observed when 1 µM of hormone/well was used. A reduction in TNF production was found with 20 and 10 µM of TS for 6 h stimulation, although increased levels were observed with 5 and 1 µM, similar to the infected control. However, there was an increase in TNF production and not after 12 h. The relative expression of parasite glycoprotein 82 was increased with the presence of TS in the medium, regardless of time. Our data suggest that TS may contribute to cellular immunosuppression, increasing parasite infection in the cell, as well as inflammatory mediators that lead to cell and tissue damage in infected individuals, as well as the possible use of TS to allow their invasion into the cell hosts.

Cafeteria diet-induced obesity remodels immune response in acute Trypanosoma cruzi infection.

BACKGROUND: Obesity is a global problem associated with several conditions, including hypertension, diabetes, arthritis and cardiovascular diseases. With the increase in the prevalence of obesity in recent years, mostly in developing countries, it is important to study its impact on various diseases, including infectious illnesses, such as Chagas disease, caused by the protozoan Trypanosoma cruzi. Considering that a diet rich in salt, sugar, and fat is associated with obesity, this study aimed to evaluate the influence of cafeteria diet (CAF)-induced obesity on immune responses in T. cruzi-infected rats. METHODS: Male Wistar Hannover rats were provided with water and food ad libitum (chow group). The CAF-fed groups received a normal rodent diet or CAF. The animals were intraperitoneally infected with 105 trypomastigote forms of the Y strain of T. cruzi present in the whole blood from a previously infected mouse. RESULTS: CAF-fed rats showed a significant increase in visceral adipose tissue weight compared to chow-fed rats. A significant reduction in CD3+ CD4+ helper splenic T cells was observed in obese-infected rats compared to non-obese-infected rats, as well as CD11b and macrophages. In addition, macrophages from obese animals displayed reduced RT1b levels compared to those from control animals. Moreover, INF-γ, an important factor in macrophage activation, was reduced in obese-infected rats compared with their counterparts. CONCLUSIONS: These results indicate that a CAF can impair the cell-mediated immune response against T. cruzi.

The Microbiota-Dependent Worsening Effects of Melatonin on Gut Inflammation.

Dysbiosis and disturbances in gut homeostasis may result in dysregulated responses, which are common in inflammatory bowel diseases (IBD). These conditions may be refractory to the usual treatments and novel therapies are still necessary to reach a more successful regulation of intestinal immunity. The hormone melatonin (MLT) has been raised as a therapeutic alternative because of its known interactions with immune responses and gut microbiota. Hence, we evaluated the effects of MLT in experimental colitis that evolves with intestinal dysbiosis, inflammation and bacterial translocation. C57BL/6 mice were exposed to dextran sulfate sodium and treated with MLT. In acute colitis, the hormone led to increased clinical, systemic and intestinal inflammatory parameters. During remission, continued MLT administration delayed recovery, increased TNF, memory effector lymphocytes and diminished spleen regulatory cells. MLT treatment reduced Bacteroidetes and augmented Actinobacteria and Verrucomicrobia phyla in mice feces. Microbiota depletion resulted in a remarkable reversion of the colitis phenotype after MLT administration, including a counter-regulatory immune response, reduction in TNF and colon macrophages. There was a decrease in Actinobacteria, Firmicutes and, most strikingly, Verrucomicrobia phylum in recovering mice. Finally, these results pointed to a gut-microbiota-dependent effect of MLT in the potentiation of intestinal inflammation.

Hypothyroidism impairs the host immune response during the acute phase of Chagas disease.

Diseases associated with thyroid hypofunction have been the subject of studies in infectious models, since several authors have demonstrated a pivotal role of iodinated hormones (thyroxine and triiodothyronine) in the modulation of immune effector responses. Using a model of hypothyroidism induced by anti-thyroid drug, we investigated the influence of hypothyroidism in the course of acute Trypanosoma cruzi infection. For this, male Hannover Wistar rats were challenged with methimazole for 21 days (0.02% in drinking water), and water for control counterparts. After confirmation of the hypothyroidism, rats were intraperitoneally challenged with 1x105 blood trypomastigotes of the Y strain of T. cruzi. Our findings suggest that hypothyroidism impairs animal weight gain, but does not affect the health of essential organs. Interestingly, infected hypothyroid animals had a significant increase in thymic cell death, with consequent drop in lymphocyte frequency in whole blood (evaluated on the 11th day of infection). Analyzing the percentage of immune cells in the spleen, we found a strong influence of hypothyroidism as a negative regulator of B cells, and antigenic ability of macrophages (RT1b expression) in the course of the experimental chagasic infection. Enhanced serum IL-17A concentration was induced by T. cruzi infection, but hypothyroidism impaired the production of this mediator as seen in infected hypothyroid animals. Taken together, our work suggests for the first time that hypothyroidism may adversely interfere with the modulation of effective immunity in the early phase of Chagas' disease.

Lesões do plexo braquial / Brachial plexus injury

A lesão do plexo braquial acarreta grave disfunção no membro superior. Pode ser resultante de qualquer trauma com energia suficiente para tracionar, romper ou até avulsionar as raízes nervosas diretamente da coluna cervical. Os mecanismos mais comuns são os acidentes de motocicletas em homens jovens. A abordagem inclui minuciosa anamnese, com identificação do mecanismo e energia do trauma, exames eletrofisiológicos e de imagem. O tratamento especializado e precoce vai oferecer as melhores chances de recuperação. Recentemente, a contribuição da microcirurgia e as técnicas de neurotização (transferência de um nervo funcionante oriundo de uma raiz nervosa sadia e anastomosada com o coto distal do nervo lesado) têm demonstrado resultados satisfatórios. O artigo revisa a etiopatogenia das lesões de plexo braquial, o diagnóstico e as condutas atuais no tema

Brachial plexus injury causes severe upper limb dysfunction. It may result from any trauma that is strong enough to pull, break up or even avulse nerve roots directly from the cervical spine. The most common mechanisms are motorcycle accidents in young men. The approach includes thorough history taking, identifying the mechanism and energy of trauma, and electrophysiological and imaging examinations. Early specialized treatment will offer the best chances of recovery. Recently, the contribution of microsurgery and the techniques of neurotization (transfer of a functioning nerve from a healthy nervous root that is anastomosed with the distal stump of the injured nerve) have shown satisfactory results. The article reviews the etiopathogeny, diagnosis and current approaches to brachial plexus injuries

Conduta atual nas síndromes compressivas do membro superior / Current approach to upper extremities entrapment neuropathies

As síndromes compressivas estão entre as causas mais comuns de queixas nos ambulatórios dos cirurgiões plásticos e ortopedistas. Os sintomas podem ser evidentes, mas muitas vezes passam despercebidos ao médico generalista. Facilmente são confundidos com sintomas vasculares, da “idade” ou somatização. O entendimento da fisiopatogenia destas lesões auxiliará no diagnóstico precoce e no tratamento mais adequado de cada caso. Neste artigo abordaremos de forma simplificada o manejo clínico, diagnóstico e a conduta nas principais síndromes compressivas do membro superior.

Compressive syndromes are among the most commons causes of complaint in the offices of plastic surgeons and orthopedists. Although the symptoms may be evident, they often go unnoticed to the primary-care physician. They are easily mistaken for vascular symptoms, “aging”, or somatization. An understanding of the physiopathogeny of such lesions will be helpful in the early diagnosis and to select the most appropriate treatment for each case. In this article we briefly address the clinical management, diagnosis, and the approach to the main compressive syndromes of the upper limbs.

Exercise performance in young and middle-aged female patients with subclinical hyperthyroidism.

Subclinical hyperthyroidism (SH) may be responsible for many cardiovascular changes, including an impaired exercise performance. The aim of our study was to evaluate the response to the treadmill cardiopulmonary test in patients with SH. We studied 14 female patients from our endocrine clinic with exogenous SH, free from cardiovascular diseases, with mean age of 38.6 +/- 10.2 years, body mass index (BMI) of 24.4 +/- 4.0 kg/m(2), and disease duration of 4.9 +/- 4.9 years. The mean serum thyrotropin (TSH) was 0.03 +/- 0.03 mU/L, serum free thyroxine (FT(4)), 1.72 +/- 0.21 ng/dL, and serum triiodothyronine level, 137 +/- 32 ng/dL. The control group comprised 15 euthyroid, healthy women, with mean age of 35.4 +/- 7.4 years and BMI of 27.3 +/- 5.9 kg/m(2). Both groups had a sedentary lifestyle and underwent the cardiopulmonary test using a treadmill with the Balke protocol. Gas concentrations and the respiratory outflow were measured and the electrocardiogram (ECG) was registered in real time. We calculated the minute ventilation (V(E)), the oxygen consumption (peak VO(2)), the carbonic gas exhalation (peak VCO(2)) and the anaerobic threshold (AT). The heart rate (HR) at rest (90.9 +/- 15.7 versus 78.9 +/- 8.7 beats per minute; p = 0.03) was higher in the patients from our clinic. There was no difference between groups regarding age, BMI, fat percentage, blood pressure, peak HR, exercise duration, mean treadmill peak inclination, V(E), peak VO(2), peak VCO(2), and AT. There was no correlation between peak VO(2) and FT(4), TSH, or disease duration. Our results show that exercise capacity in young and middle-aged female patients is not significantly affected by exogenous SH.