Sugar-sweetened soft drinks consumption and risk of hyperuricemia: Results of the ELSA-Brasil study.

BACKGROUND AND AIMS: The prospective association between sugar-sweetened beverages consumption and hyperuricemia is controversial. The aim was to investigate the association of the consumption of sugar-sweetened soft drinks and unsweetened fruit juices with the incidence of hyperuricemia and the levels of serum uric acid in the participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS AND RESULTS: Longitudinal analysis in ELSA-Brasil participants (baseline 2008-2010 and follow-up 2012-2014). The sample consisted of 10,072 civil servants (35-74 years, both sexes). The consumption of beverages estimated by a food frequency questionnaire (baseline) was divided into five categories: nonconsumption and quartiles (≥0.1 mL/day). Hyperuricemia was defined as uric acid ≥7.0 mg/dL (men) and ≥5.7 mg/dL (women). Poisson regression with robust variance and multiple linear regression were tested. The average consumption of soft drinks was 84 ± 191 mL/day in men and 42 ± 128 mL/day in women. After 4 years of follow-up, the higher consumption of soft drinks (men: 401 ± 303 mL/day; women: 390 ± 290 mL/day) increased the relative risk of hyperuricemia by 30% (men) and 40% (women), and was associated with increased mean uric acid (men: ß = 0.14 mg/dL; 95% CI 0.41-0.24; women: ß = 0.11 mg/dL; 95% CI 0.00-0.21). The consumption of unsweetened juice was not associated with hyperuricemia. CONCLUSION: High consumption of sugar-sweetened soft drinks is associated with an increased relative risk of hyperuricemia and elevated serum uric acid levels in Brazilian adults.

Decreased invariant natural killer T-cell-mediated antitumor immune response in patients with gastric cancer.

Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Invariant natural killer T (iNKT) cells are innate-like cytotoxic T lymphocytes involved in tumor immune surveillance. They can be activated either through CD1d-presented glycolipid antigens recognized by their invariant T-cell receptor, cytokines or by sensing tumor-associated stress-induced ligands through the natural killer group 2, member D (NKG2D) receptor. Although the number and functionality of iNKT cells may be decreased in several types of cancer, here we show that GC patients presented a mild increase in iNKT cell frequencies and numbers in the blood compared with healthy donors. In GC patients, iNKT cells, expanded in vitro with α-galactosyl ceramide and stimulated with phorbol 12-myristate 13-acetate and ionomycin, produced higher levels of interleukin-2 and transforming growth factor-beta, while their capacity to degranulate remained preserved. Because tumor-derived epithelial cell adhesion molecule-positive epithelial cells did not display surface CD1d, and NKG2D ligands (NKG2DLs) were detected in the gastric tumor milieu, we envisioned a role for NKG2D in iNKT cell functions. Peripheral iNKT cells from GC patients and controls presented similar levels of NKG2D; nevertheless, the percentages of interferon-γ-producing and CD107a-positive iNKT cells from patients were reduced upon challenge with CD1d-negative, NKG2DL-positive K562 cells, suggesting a compromised response by iNKT cells in GC patients, which may not result from impaired NKG2D/NKG2DL signaling. The decreased response of iNKT cells may explain the fact that higher frequencies of circulating iNKT cells did not confer a survival benefit for GC patients. Therefore, functional impairment of iNKT cells in GC may contribute to tumor immune escape and favor disease progression.

Different Responses in Mandarin Cultivars Uncover a Role of Cuticular Waxes in the Resistance to Citrus Canker.

'Okitsu' is a mandarin cultivar showing substantial resistance to X. citri subsp. citri (X. citri). We have previously shown that this cultivar has significantly lower canker incidence and severity than 'Clemenules', particularly during early stages of leaf development in the field. This differential response is only seen when the leaves are inoculated by spraying, suggesting that leaf surface contributes to resistance. In this work, we have studied structural and chemical properties of leaf surface barriers of both cultivars. Ultrastructural analysis showed a thicker cuticle covering epidermal surface and guard cells in young 'Okitsu' leaves than in 'Clemenules'. This thicker cuticle was associated with a smaller stomatal aperture and reduced cuticle permeability. These findings correlated with an accumulation of cuticular wax components, including primary alcohols, alkanes, and fatty acids. None of these differences were observed in mature leaves, where both cultivars are equally resistant to the bacterium. Remarkably, mechanical alteration of cuticular thickness of young 'Okitsu' leaves allows canker development. Furthermore, cuticular waxes extracted from young 'Okitsu' leaves have higher antibacterial activity against X. citri than 'Clemenules'. Taken together, these data suggest that a faster development of epicuticular waxes in 'Okitsu' leaves play a central role in its resistance to X. citri.

Blocking of p38 and transforming growth factor ß receptor pathways impairs the ability of tolerogenic dendritic cells to suppress murine arthritis.

OBJECTIVE: Dendritic cells (DCs) modulated with lipopolysaccharide (LPS) are able to reduce inflammation when therapeutically administered into mice with collagen-induced arthritis (CIA). The aim of this study was to uncover the mechanisms that define the tolerogenic effect of short-term LPS-modulated DCs on CIA. METHODS: Bone marrow-derived DCs were stimulated for 4 hours with LPS and characterized for their expression of maturation markers and their cytokine secretion profiles. Stimulated cells were treated with SB203580 or SB431542 to inhibit the p38 or transforming growth factor ß (TGFß) receptor pathway, respectively, or were left unmodified and, on day 35 after CIA induction, were used to inoculate mice. Disease severity was evaluated clinically. CD4+ T cell populations were counted in the spleen and lymph nodes from inoculated or untreated mice with CIA. CD4+ splenic T cells were transferred from mice with CIA treated with LPS-stimulated DCs or from untreated mice with CIA into other mice with CIA on day 35 of arthritis. RESULTS: Treatment with LPS-stimulated DCs increased the numbers of interleukin-10 (IL-10)-secreting and TGFß-secreting CD4+ T cells, but decreased the numbers of Th17 cells. Adoptive transfer of CD4+ T cells from treated mice with CIA reproduced the inhibition of active CIA accomplished with LPS-stimulated DCs. The therapeutic effect of LPS-stimulated DCs and their influence on T cell populations were abolished when the p38 and the TGFß receptor pathways were inhibited. CONCLUSION: DCs modulated short-term (4 hours) with LPS are able to confer a sustained cure in mice with established arthritis by re-educating the CD4+ T cell populations. This effect is dependent on the p38 and the TGFß receptor signaling pathways, which suggests the participation of IL-10 and TGFß in the recovery of tolerance.

Nutritional extremes among school children in a rural Brazilian municipality.

INTRODUCTION: Latin America is undergoing rapid demographic and nutritional transitions with the accompanying tendency to overweight as is common in countries emerging from poverty. In Brazil, changes due to the nutritional transition have affected the whole population, both urban and rural. Overweight in a large number of Brazilian children is one of the greatest public policy challenges. The objective of this 2009-2010 study was to estimate the prevalence of nutritional extremes among children from 7 to 10 years of age in a rural municipality on the state of Espírito Santo, Brazil. METHODS: The sample consisted of 901 school children. Socio-demographic (sex, school location, age and skin color) and anthropometric (weight and height) data were collected, as well as information on eating habits (breakfast, number of meals and presence of a companion during meals). The nutritional status was classified according to BMI per age with the cut-off points: BMI for age < 3rd percentile = underweight and BMI per age > 97th percentile = obesity. RESULTS: A prevalence of 3.4% underweight and 5% obesity was observed, the latter higher in urban areas (p<0.05). Living in an urban area and the habit of eating four or fewer meals/day were associated with obesity among children. Among urban located children 7.5% obesity was found, approximately twice that of rural children. CONCLUSION: Underweight has been regressing, possibly due to improvements in access to health and better living conditions, even in rural areas. However obesity was associated with this in the urban location of the area studied. Children who studied and lived in rural areas showed a lower prevalence of obesity, possibly due to lower socioeconomic conditions and more intense physical activity in their daily activities. The habit of eating four or fewer meals was associated with obesity. This could be explained by the alteration it causes to biological mechanisms. The promotion of physical activity is proposed, mainly in urban areas, and nutritional education aimed at improve eating habits in both urban and rural areas.

Food insecurity and nutritional status among older adults: a systematic review.

CONTEXT: Food insecurity (FI), characterized by difficulty or inability to access adequate food, has become a public health problem. OBJECTIVE: To analyze studies relating FI with nutritional status (NS) among older adults and the associated factors. DATA SEARCH: Articles published up to June 2020 were investigated in 5 databases: PubMed, Embase, Scopus, LILACS, and Web of Science. The search, selection, extraction, and quality evaluation were carried out by 2 reviewers. DATA EXTRACTION: The authors identified characteristics of the studies and the main data regarding the relationship of interest. RESULTS: Twenty-two studies were included in the review and their characteristics are summarized and presented using narrative synthesis. In 10 studies (45.4%), a relationship was observed between FI and malnutrition; in another 6 (27.3%), a relationship was observed between FI and being overweight. CONCLUSION: A relationship was identified between FI, especially severe forms, and malnutrition, as well as between FI, especially mild forms, and people being overweight. Thus, FI among older adults relates to a 2-fold burden of nutritional outcomes, depending on the level. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020185086.

Oxidative stress induced by a commercial glyphosate formulation in a tolerant strain of Chlorella kessleri.

We studied the toxicity of a glyphosate formulation and provide evidence of metabolic alterations due to oxidative stress caused in a Chlorella kessleri tolerant strain by exposure to the herbicide. After 96 h of exposure to increasing concentrations of the herbicide (0-70 mg L(-1)) with alkylaryl polyglycol ether surfactant, growth was inhibited (EC50-96 h 55.62 mg L(-1)). Glyphosate increased protein and malondialdehyde content which was significantly higher than in the control at 50-70 mg L(-1). Superoxide dismutase and catalase activities and reduced glutathione levels increased in a concentration-dependant manner. Morphological studies showed increases in vacuolisation and in cell and sporangia sizes. The glyphosate formulation studied has a cytotoxic effect on C. kessleri through a mechanism that would involve the induction of oxidative stress. Upon glyphosate exposure, oxidative stress parameters such as SOD and CAT activities and MDA level could be more sensitive biomarkers than usually tested growth parameters in C. kessleri.

Alcoholic beverage consumption, changes in blood pressure, and incidence of hypertension in the Longitudinal Adult Health Study (ELSA-Brasil).

OBJECTIVES: Alcohol consumption is generally associated with increased risk of hypertension. We aimed to investigate, prospectively, the effect of alcoholic-beverage consumption on blood pressure (BP) and incidence of hypertension, after a 4-y follow-up, in participants of the Longitudinal Adult Health Study (ELSA-Brasil). METHODS: We analyzed information from 3,990 participants (ages 35-74 y), men and women, from educational and research institutions, at baseline (2008-2010) and follow-up (2012-2014). Socioeconomic, hemodynamic, anthropometric, and health data were collected. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg and/or use of antihypertensive medication. Change in alcohol consumption (g/d) was estimated by subtracting total consumed at follow-up from total consumed at baseline, and was categorized in tertiles. RESULTS: The consumption of alcoholic beverages was associated with changes in BP and hypertension only in men. Individuals who reduced total consumption of alcohol showed a smaller increase in systolic BP (1.1 versus 2.3 mm Hg; P = 0.03) and diastolic BP (1.3 versus 2.2 mm Hg; P = 0.008) compared to individuals who increased consumption. In addition, individuals in the highest tertiles of total consumption of alcohol (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.14-2.29) and consumption of beer (OR, 1.51; 95% CI, 1.07-12.13), wine (OR, 1.71; 95% CI, 1.01-2.86), and spirits (OR, 2.01; 95% CI, 1.21-3.32) showed higher odds ratios for hypertension compared to the lowest tertile. CONCLUSIONS: Increased consumption of alcoholic beverages was positively associated with increased BP levels and higher chances of developing hypertension in men.

Diet and Lifestyle Changes During the COVID-19 Pandemic in Ibero-American Countries: Argentina, Brazil, Mexico, Peru, and Spain.

This study aimed to evaluate changes in dietary and lifestyle habits during the period of confinement due to the first wave of the COVID-19 pandemic in Ibero-American countries. A cross-sectional investigation was conducted with 6,325 participants of both genders (68% women), over 18 years of age and from five countries: Brazil (N = 2,171), Argentina (N = 1,111), Peru (N = 1,174), Mexico (N = 686), and Spain (N = 1,183). Data were collected during the year 2020, between April 01 and June 30 in Spain and between July 13 and September 26, in the other countries studied using a self-administered online survey designed for the assessment of sociodemographic, employment, physical activity, health status, and dietary habits changes. Most participants (61.6%), mainly those from Spain, remained constant, without improving or worsening their pattern of food consumption. Among those who changed, a pattern of better eating choices prevailed (22.7%) in comparison with those who changed toward less healthy choices (15.7%). Argentina and Brazil showed the highest proportion of changes toward a healthier pattern of food consumption. Peruvians and Mexicans were less likely to make healthy changes in food consumption (OR: 0.51; 95% CI: 0.4-0.6 and OR: 0.69; 95% CI: 0.4-0.8, respectively), when compared to Argentinians. Most respondents did not change their pattern of meal consumption, but those who did reduced their consumption of main meals and increased intake of small meals and snacks. Although most participants affirmed to be doing physical activity at home, about one-half reported perception of weight gain. Individuals with alterations in sleep pattern (either by increasing or decreasing sleep time) were more likely to change their diets to a healthier pattern. In contrast, individuals with confirmed diagnosis of COVID-19 and those who reported feeling anxious were more likely to perform changes to a less healthy eating pattern (OR: 1.72; 95% CI: 1.2-2.3 and OR: 1.21; 95% CI: 1.1-1.4, respectively). In conclusion, although most participants remained constant in their eating habits, lifestyle changes and anxiety feelings were reported. Among those who changed patterns of food consumption, healthier choices prevailed, with differences between countries. However, there were alterations in the distribution of meals, with higher consumption of snacks and small meals. These results can be used to guide policies to prevent deleterious consequences that may affect the incidence of chronic diseases.

Physiological and Proteomic Changes in the Apoplast Accompany Leaf Senescence in Arabidopsis.

The apoplast, i.e. the cellular compartment external to the plasma membrane, undergoes important changes during senescence. Apoplastic fluid volume increases quite significantly in senescing leaves, thereby diluting its contents. Its pH elevates by about 0.8 units, similar to the apoplast alkalization in response to abiotic stresses. The levels of 159 proteins decrease, whereas 24 proteins increase in relative abundance in the apoplast of senescing leaves. Around half of the apoplastic proteins of non-senescent leaves contain a N-terminal signal peptide for secretion, while all the identified senescence-associated apoplastic proteins contain the signal peptide. Several of the apoplastic proteins that accumulate during senescence also accumulate in stress responses, suggesting that the apoplast may constitute a compartment where developmental and stress-related programs overlap. Other senescence-related apoplastic proteins are involved in cell wall modifications, proteolysis, carbohydrate, ROS and amino acid metabolism, signaling, lipid transport, etc. The most abundant senescence-associated apoplastic proteins, PR2 and PR5 (e.g. pathogenesis related proteins PR2 and PR5) are related to leaf aging rather than to the chloroplast degradation program, as their levels increase only in leaves undergoing developmental senescence, but not in dark-induced senescent leaves. Changes in the apoplastic space may be relevant for signaling and molecular trafficking underlying senescence.

[Prevalence of metabolic syndrome in population-based study, Vitória, ES-Brazil]. / Prevalência de síndrome metabólica em estudo de base populacional, Vitória, ES-Brasil.

Metabolic Syndrome (MS) is a complex disorder including several factors predisposing to development of cardiovascular diseases and diabetes. Despite the importance of MS for the health system, the epidemiological characteristics of this condition in the Brazilian population are still scarce. The prevalence of MS as a function of gender, age and socioeconomic level was determined in a population-based study in Vitória, ES, Brazil, by using the NCEP-ATPIII diagnosis criteria. Socioeconomic, biochemical, anthropometric, and hemodynamic data were obtained in 1,663 individuals from a random sample of Vitória population (25-64 y). The estimated prevalence of MS was 29,8% (CI95 = 28-32%). No significant sex-related differences were observed. Prevalence increased from the youngest (26-34 y) to the oldest (55-64 y) group (15.8% and 48.3%, respectively). A progressive increase of MS frequency was observed in women from the higher to the lowest socioeconomic level. The most frequent trait of MS in males was high blood pressure, followed by hypertriglyceridemia, low HDL-c levels, hyperglycemia, and central obesity. In females, hypertension was also the most frequent factor, followed by low HDL-c levels, abdominal obesity, hypertriglyceridemia and hyperglycemia. Our data show that prevalence of MS is high in the studied population, even in the youngest group. Moreover, high blood pressure gives a significant contribution to the diagnosis of this syndrome in both sexes. The precocious control of risk factors is necessary to reduce the impact of cardiovascular morbidity and mortality.

Dexamethasone and Monophosphoryl Lipid A Induce a Distinctive Profile on Monocyte-Derived Dendritic Cells through Transcriptional Modulation of Genes Associated With Essential Processes of the Immune Response.

There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, the molecular bases that drive the differentiation of monocyte-derived DCs (moDCs) toward a tolerogenic state are still poorly understood. Here, we studied the transcriptional profile of moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), referred to as Dex-modulated and MPLA-activated DCs (DM-DCs), as an approach to identify molecular regulators and pathways associated with the induction of tolerogenic properties in tolDCs. We found that DM-DCs exhibit a distinctive transcriptional profile compared to untreated (DCs) and MPLA-matured DCs. Differentially expressed genes downregulated by DM included MMP12, CD1c, IL-1B, and FCER1A involved in DC maturation/inflammation and genes upregulated by DM included JAG1, MERTK, IL-10, and IDO1 involved in tolerance. Genes related to chemotactic responses, cell-to-cell signaling and interaction, fatty acid oxidation, metal homeostasis, and free radical scavenging were strongly enriched, predicting the activation of alternative metabolic processes than those driven by counterpart DCs. Furthermore, we identified a set of genes that were regulated exclusively by the combined action of Dex and MPLA, which are mainly involved in the control of zinc homeostasis and reactive oxygen species production. These data further support the important role of metabolic processes on the control of the DC-driven regulatory immune response. Thus, Dex and MPLA treatments modify gene expression in moDCs by inducing a particular transcriptional profile characterized by the activation of tolerance-associated genes and suppression of the expression of inflammatory genes, conferring the potential to exert regulatory functions and immune response modulation.

An in vivo role for Trypanosoma cruzi calreticulin in antiangiogenesis.

Angiogenesis leads to neovascularization from existing blood vessels. It is associated with tumor growth and metastasis and is regulated by pro- and antiangiogenic molecules, some of them currently under clinical trials for cancer treatment. During the last few years we have cloned, sequenced and expressed a Trypanosoma cruzi calreticulin gene (TcCRT). Its product, TcCRT, a 45 kDa protein, is more than 50% identical to human CRT (HuCRT). TcCRT, present on the surface of trypomastigotes, binds both C1q and mannan binding lectin and inhibits the classical activation pathway of human complement. Since TcCRT is highly homologous to a functional antiangiogenic fragment from HuCRT (aa 120-180), recombinant (r) and native (n) TcCRT were tested in their antiangiogenic effects, in the chick embryonic chorioallantoid membrane (CAM) assay. Both proteins mediated highly significant antiangiogenic effects in the in vivo CAM assay. This effect was further substantiated in experiments showing that the plasmid construct pSecTag/TcCRT also displayed significant antiangiogenic properties, as compared to the empty vector. Most likely, the fact that antiangiogenic substances act preferentially on growing neoplasic tissues, but not on already established tumors, is due to their effects on emerging blood vessels. The results shown here indicate that TcCRT, like its human counterpart, has antiangiogenic properties. These properties may explain, at least partly, the reported antineoplasic effect of experimental T. cruzi infection.

Phytotoxicity and genotoxicity assessment of imazethapyr herbicide using a battery of bioassays.

The imazethapyr herbicide (formulation Verosil(®)) was evaluated for phytotoxicity and genotoxicity using a battery of bioassays: (1) the growth inhibition of the green alga Pseudokirchneriella subcapitata, (2) the root growth and germination of the higher plant Lactuca sativa, (3) the genetic damage using the Salmonella/microsome test, and (4) the aneugenic and clastogenic effects on Allium cepa. The Verosil(®) formulation was highly toxic to the non-target green alga (median effective concentration (EC50) = 1.05 ± 0.05 mg active ingredient (a.i.) L(-1)), and concentrations above 10 mg a.i. L(-1) inhibited root elongation in lettuce: relative growth index (RGI) between 0.28 ± 0.01 and 0.66 ± 0.10. No genotoxic effect was observed in S almonella typhimurium at 100 mg a.i. L(-1), either with or without the microsomal fraction. However, significant differences in the frequency of chromosomal aberrations in anaphases and telophases (bridges, chromosome fragments, and vagrants) were observed in A. cepa at concentrations between 0.01 and 1 mg a.i. L(-1) with respect to the control. The frequencies of micronuclei showed significant differences with respect to the control at concentrations between 0.001 and 0.1 mg a.i. L(-1). A very high mitotic index (MI = 93.8 ± 5.8) was observed associated with a high number of cells in the prophase stage at 100 mg a.i. L(-1), indicating cytotoxicity. These results showed that imazethapyr is toxic to the non-target populations in both aquatic and terrestrial ecosystems. This herbicide might also exert clastogenic and aneugenic mitotic damage in higher plants. Therefore, the imazethapyr formulation may constitute an environmental risk to plants.

Trypanosoma cruzi calreticulin: a novel virulence factor that binds complement C1 on the parasite surface and promotes infectivity.

In Trypanosoma cruzi, calreticulin (TcCRT) translocates from the endoplasmic reticulum (ER) to the area of flagellum emergence. We propose herein that the parasite uses this molecule to capture complement C1, in an infective apoptotic mimicry strategy. Thus, TcCRT/C1 interactions, besides inhibiting the classical pathway of complement activation as previously shown in our laboratories, will also promote infectivity. This fact correlates with significant increases in TcCRT mRNA levels during early infection stages of a VERO cell line. In vitro, the collagenous and globular C1q domains simultaneously bind TcCRT and antigen aggregated Igs, respectively. Accordingly, mouse immunizations with TcCRT induced humoral responses that, after challenge, correlated with increased parasitemia. Thus, on the parasite surface, whole Igs anti-TcCRT promote C1 deposits on trypomastigotes while, as expected, F(ab')2 fragments decrease it. Likewise, pretreatment of the parasites with whole anti-TcCRT antibodies augmented parasitemia and mortality in mice. In contrast, pretreatment with F(ab')2 fragments anti-TcCRT, devoid of their capacity to provide additional C1q binding sites, was protective. Most important, while pretreatment of trypomastigotes with C1q increased infectivity in the RAW murine cell line, as well as mice mortality and parasitemia, the F(ab')2 fragments significantly interfered with the C1q-dependent infectivity. Differently from other surface molecules involved in infectivity, TcCRT uses C1 as an adaptor molecule to recognize host cells. As expected, since TcCRT is one of several cell surface parasite molecules participating in infectivity, attempts to interfere with the C1/TcCRT interactions with F(ab')2 fragments, were moderately but significantly effective, both in vitro and in vivo.

Oxidative stress in vero cells infected with vesicular stomatitis virus.

Viral-induced apoptosis might be mediated by oxidative stress. It has already been described that cell death in vesicular stomatitis virus (VSV)-infected cells occurs by apoptosis. In this study, oxidative stress parameters present in VSV-infected Vero cells were analyzed. Lipid peroxides (LP) were evaluated in cellular extracts and expressed as thiobarbituric acid-reactive substances. LP levels exhibited a rise at different times post infection, according to the multiplicity of infection (MOI), while the presence of cycloheximide determined a reduction on LP. Also, an increase in protein degradation products and a decrease in polyunsaturated fatty acids content was observed, indicating that cellular proteins and lipids began to be susceptible to degradation during VSV infection. In addition, we analyzed cell viability of VSV-infected Vero cells, which were incubated in the presence of butylated hydroxyanisole. This antioxidant was able to protect Vero cells, at least at MOIs assayed in this study, and to reduce viral yield only when VSV infection was done at MOI 0.05. Further, superoxide dismutases, which occupy the first step within the antioxidant enzyme cascade, also exhibit a rise in VSV-infected Vero cells, at different MOI. These results suggest that both an oxidative stress and an antioxidative cell response precede the induction of apoptosis by VSV.

F(ab')2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement.

Trypanosoma cruzi calreticulin (TcCRT), described in our laboratory, retains several important functional features from its vertebrate homologues. We have shown that recombinant TcCRT inhibits the human complement system when it binds to the collagenous portion of C1q. The generation of classical pathway convertases and membrane attack complexes is thus strongly inhibited. In most T. cruzi-infected individuals, TcCRT is immunogenic and mediates the generation of specific antibodies. By reverting the C1q / TcCRT interaction, a parasite immune evasion strategy, these antibodies contribute to the host/parasite equilibrium. In an in vitro correlate of this situation, we show that the Clq/TcCRT interaction is inhibited by F(ab')2 polyclonal anti-TcCRT IgG fragments. It is therefore feasible that in infected humans anti-TcCRT antibodies participate in reverting an important parasite strategy aimed at inhibiting the classical complement pathway. Thus, membrane-bound TcCRT interacts with the collagenous portion Clq, and this Clq is recognized by the CD91-bound host cell CRT, thus facilitating parasite internalization. Based on our in vitro results, it could be proposed that the in vivo interaction between TcCRT and vertebrate Clq could be inhibited by F(ab')2 fragments anti-rTcCRT or against its S functional domain, thus interfering with the internalization process.

An anti-human recombinant tumor necrosis factor alpha (TNF alpha) monoclonal antibody recognizes an epitope in feline TNF alpha.

It is likely that the murine response to human recombinant TNF alpha (hrTNF alpha) may generate antibodies (Ab) to epitopes present in TNF alpha from other species. Here, we demonstrate that F5 anti-hrTNF alpha monoclonal antibody (mAb) recognizes feline TNF alpha while E8 anti-hrTNF alpha mAb failed to do so. In order to demonstrate that E8 and F5 mAb recognize different epitopes in the hrTNF alpha molecule, a constant concentration of E8 and variable concentrations of F5 were incubated with solid phase bound hrTNF alpha. Binding of E8 and F5 to hrTNF alpha was determined with anti-mu and gamma chain specific Ab. F5 bound equally to hrTNF alpha in the presence or absence of E8 and the same amount of E8 bound to hrTNF alpha, in spite of the presence of F5. When using the E8 and F5 mAb for capturing the TNF alpha from the equine, canine, feline and bovine species, in supernatants of an ex vivo lipopolysaccharide (LPS)-stimulated whole blood cell culture, we only detected the feline TNF alpha by F5 mAb (p = 0.001). By a cytotoxic assay on L929 fibroblasts, we indeed demonstrated the feline TNF alpha production after the LPS stimulus. In an inhibition assay, the human and feline cytokines competed for F5, although the inhibition of native human TNF alpha binding to F5 was significant but only about 20% (p = 0.001). In conclusion, most likely the F5 anti-hrTNF alpha mAb recognizes an epitope in feline TNF alpha. Its immunomodulatory potential in the feline model remains to be studied.

A simple immunometric assay to assess the feeding habits of Meprai spinolai, a Trypanosoma cruzi vector.

We propose a simple assay to assess the importance of seven vertebrate species as food sources for Mepria spinolai, a wild arthropod vector of Trypanosoma cruzi (the agent of Chagas' disease). Rabbits were immunized with serum proteins from one of each of the seven species. After titration, a consensus 1/100,000 dilution of the immune sera detected vertebrate serum proteins in the intestinal contents of 48.9% of 131 insects tested. The high proportion of negative samples is consistent with previous information indicating that these insects can withstand prolonged fasting periods. Alternatively, they may have fed on a different animal species than those used to produce the antisera. In about 70% of the positive samples, only one species of serum protein was detected. All pre-immune sera were negative. In 67% of the positive vectors, rabbit immunoglobulins were detected directly by means of a specific goat antibody. Thus, rabbits may play a role in T. cruzi transmission.

Prevalência de síndrome metabólica em estudo de base populacional, Vitória, ES - Brasil / Prevalence of metabolic syndrome in population-based study, Vitória, ES - Brazil

Síndrome Metabólica (SM) é um transtorno representado pela agregação de fatores predisponentes para desenvolvimento de doenças cardiovasculares e diabetes. Apesar da importância da SM, há carência de dados sobre as características epidemiológicas desta condição na população brasileira. Determinamos a prevalência da SM por sexo, faixa etária e nível socioeconômico na população da cidade de Vitória, ES, Brasil, utilizando os critérios do NCEP/ATPIII. Foram coletados dados socioeconômicos, bioquímicos, antropométricos e hemodinâmicos em 1.663 indivíduos de amostra randômica da população (25-64 anos) de Vitória. A prevalência foi de 29,8 por cento (IC95 = 28-32 por cento), sem diferença entre sexos. De 25 a 34 anos, a prevalência foi 15,8 por cento, alcançando 48,3 por cento na faixa de 55 a 64 anos. Verificou-se aumento progressivo de prevalência em mulheres do maior para o menor nível socioeconômico. O parâmetro da SM mais freqüente em homens foi hipertensão, seguido de hipertrigliceridemia, baixo HDL-colesterol, hiperglicemia e obesidade abdominal. Nas mulheres, hipertensão em primeiro lugar, seguida do baixo HDL-colesterol, obesidade abdominal, hipertrigliceridemia e hiperglicemia. Conclui-se que a prevalência de SM é elevada, inclusive nos mais jovens, com grande contribuição da hipertensão para o seu diagnóstico. Controle dos fatores de risco deve ser promovido visando reduzir o impacto das doenças cardiovasculares na mortalidade geral.

Metabolic Syndrome (MS) is a complex disorder including several factors predisposing to development of cardiovascular diseases and diabetes. Despite the importance of MS for the health system, the epidemiological characteristics of this condition in the Brazilian population are still scarce. The prevalence of MS as a function of gender, age and socioeconomic level was determined in a population-based study in Vitória, ES, Brazil, by using the NCEP-ATPIII diagnosis criteria. Socioeconomic, biochemical, anthropometric, and hemodynamic data were obtained in 1,663 individuals from a random sample of Vitória population (25-64 y). The estimated prevalence of MS was 29,8 percent (CI95 = 28-32 percent). No significant sex-related differences were observed. Prevalence increased from the youngest (26-34 y) to the oldest (55-64 y) group (15.8 percent and 48.3 percent, respectively). A progressive increase of MS frequency was observed in women from the higher to the lowest socioeconomic level. The most frequent trait of MS in males was high blood pressure, followed by hypertriglyceridemia, low HDL-c levels, hyperglycemia, and central obesity. In females, hypertension was also the most frequent factor, followed by low HDL-c levels, abdominal obesity, hypertriglyceridemia and hyperglycemia. Our data show that prevalence of MS is high in the studied population, even in the youngest group. Moreover, high blood pressure gives a significant contribution to the diagnosis of this syndrome in both sexes. The precocious control of risk factors is necessary to reduce the impact of cardiovascular morbidity and mortality.