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.

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 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.

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.

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.

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.

Función fagocítica de los leucocitos polimorfonucleares neutrófilos (PMN) en pacientes hemofílicos / Phagocytic function of neutrophilic polymorphonuclear leukocytes (NPM) in hemophilic patients

Se estudió la función fagocitíca de los leucocitos polimorfonucleares neutrófilos (PMN) en un grupo de 25 pacientes hemofílicos con edades comprendidas entre 10 y 58 años. Todos los pacientes recibieron tratamiento con crioprecipitado. Los resultados de la ingestiòn y opsonización no presentaron diferencias estadísticamente significativas al compararlos con el grupo control: sin embargo, el porcentaje de PMN adherentes en los pacientes hemofílicos resultó significativamente elevado (pacientes 95,7% + 1,96; controles 88,7 + 5,35%)