Effects of a methanolic fraction of soybean seeds on the transcriptional activity of peroxisome proliferator-activated receptors (PPAR)

Since the anti-inflammatory, antidiabetic and hypolipidemic effects of soy isoflavones may be mediated by activation of peroxisome proliferator-activated receptors (PPAR), the present study investigated whether the methanolic fractions obtained from soybean seeds (E1) and soybean seed coats with hypocotyls (E2) could influence PPARα, PPARγ and PPARβ/δ transcriptional activity. The isoflavones from E1 and E2 were quantified by HPLC analysis. E1 and E2 were rich in isoflavones (daidzin, glycitin, genistin, malonyldaidzin, malonylglycitin, malonylgenistin, daidzein, glycitein, and genistein). Moreover, E1 and E2 showed no evidence of genetically modified material containing the gene CP4 EPSPS. To investigate PPAR transcriptional activity, human promonocytic U-937 cells were treated with E1 and E2 (200, 400, 800, and 1600 µg/mL), positive controls or vehicle. Data are reported as fold-activation of the luciferase reporter driven by the PPAR-responsive element. Dose-response analysis revealed that E1 and E2 induced the transcriptional activity of PPARα (P < 0.001), with activation comparable to that obtained with 0.1 mM bezafibrate (positive control) at 1600 µg/mL (4-fold) and 800 µg/mL (9-fold), respectively. In addition, dose-response analysis revealed that E1 and E2 activated PPARβ/δ (P < 0.05), and the activation at 800 µg/mL (4- and 9-fold, respectively) was comparable to that of 0.1 mM bezafibrate (positive control). However, no effect on PPARγ was observed. Activation of PPARα is consistent with the lipid-lowering activity of soy isoflavones in vivo, but further studies are needed to determine the physiological significance of PPARβ/δ activation.

Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL). The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Outcomes and organ dysfunctions of critically ill patients with systemic lupus erythematosus and other systemic rheumatic diseases

Our objective was to compare the pattern of organ dysfunctions and outcomes of critically ill patients with systemic lupus erythematosus (SLE) with patients with other systemic rheumatic diseases (SRD). We studied 116 critically ill SRD patients, 59 SLE and 57 other-SRD patients. The SLE group was younger and included more women. Respiratory failure (61%) and shock (39%) were the most common causes of ICU admission for other-SRD and SLE groups, respectively. ICU length-of-stay was similar for the two groups. The 60-day survival adjusted for the groups’ baseline imbalances was not different (P = 0.792). Total SOFA scores were equal for the two groups at admission and during ICU stay, although respiratory function was worse in the other-SRD group at admission and renal and hematological functions were worse in the SLE group at admission. The incidence of severe respiratory dysfunction (respiratory SOFA >2) at admission was higher in the other-SRD group, whereas severe hematological dysfunction (hematological SOFA >2) during ICU stay was higher in the SLE group. SLE patients were younger and displayed a decreased incidence of respiratory failure compared to patients with other-SRDs. However, the incidences of renal and hematological failure and the presence of shock at admission were higher in the SLE group. The 60-day survival rates were similar.

Pain-related diseases and sleep disorders

Pain and sleep share mutual relations under the influence of cognitive and neuroendocrine changes. Sleep is an important homeostatic feature and, when impaired, contributes to the development or worsening of pain-related diseases. The aim of the present review is to provide a panoramic view for the generalist physician on sleep disorders that occur in pain-related diseases within the field of Internal Medicine, such as rheumatic diseases, acute coronary syndrome, digestive diseases, cancer, and headache.

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

Extracellular vesicles: structure, function, and potential clinical uses in renal diseases

Interest in the role of extracellular vesicles in various diseases including cancer has been increasing. Extracellular vesicles include microvesicles, exosomes, apoptotic bodies, and argosomes, and are classified by size, content, synthesis, and function. Currently, the best characterized are exosomes and microvesicles. Exosomes are small vesicles (40-100 nm) involved in intercellular communication regardless of the distance between them. They are found in various biological fluids such as plasma, serum, and breast milk, and are formed from multivesicular bodies through the inward budding of the endosome membrane. Microvesicles are 100-1000 nm vesicles released from the cell by the outward budding of the plasma membrane. The therapeutic potential of extracellular vesicles is very broad, with applications including a route of drug delivery and as biomarkers for diagnosis. Extracellular vesicles extracted from stem cells may be used for treatment of many diseases including kidney diseases. This review highlights mechanisms of synthesis and function, and the potential uses of well-characterized extracellular vesicles, mainly exosomes, with a special focus on renal functions and diseases.

Classical and recent advances in the treatment of inflammatory bowel diseases

Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.

Disentangling the effects of insomnia and night work on cardiovascular diseases: a study in nursing professionals

Cardiovascular diseases (CVDs) are known to be associated with poor sleep quality in general populations, but they have not been consistently associated with specific work schedules. Studies of CVD generally do not simultaneously consider sleep and work schedules, but that approach could help to disentangle their effects. We investigated the association between insomnia and a self-reported physician diagnosis of CVD in day and night workers, considering all sleep episodes during nocturnal and diurnal sleep. A cross-sectional study was conducted in 1307 female nursing professionals from 3 public hospitals, using baseline data from the “Health and Work in Nursing - a Cohort Study.” Participants were divided into two groups: i) day workers with no previous experience in night shifts (n=281) and whose data on insomnia were related to nocturnal sleep and ii) those who worked exclusively at night (n=340) and had data on both nocturnal and diurnal sleep episodes, as they often sleep at daytime. Multiple logistic regression analysis was performed. Among day workers, insomnia complaints increased the odds of CVD 2.79-fold (95% CI=1.01-6.71) compared with workers who had no complaints. Among night workers, reports of insomnia during both nocturnal and diurnal sleep increased the odds of reported CVD 3.07-fold (95% CI=1.30-7.24). Workers with insomnia had similar probabilities of reporting CVD regardless of their work schedule, suggesting a relationship to insomnia and not to night work per se. The results also highlighted the importance of including evaluation of all sleep episodes (diurnal plus nocturnal sleep) for night workers.

The role of necroptosis in neurosurgical diseases

Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.

Association between NOx exposure and deaths caused by respiratory diseases in a medium-sized Brazilian city

Exposure to nitrogen oxides (NOx) emitted by burning fossil fuels has been associated with respiratory diseases. We aimed to estimate the effects of NOx exposure on mortality owing to respiratory diseases in residents of Taubaté, São Paulo, Brazil, of all ages and both sexes. This time-series ecological study from August 1, 2011 to July 31, 2012 used information on deaths caused by respiratory diseases obtained from the Health Department of Taubaté. Estimated daily levels of pollutants (NOx, particulate matter, ozone, carbon monoxide) were obtained from the Centro de Previsão de Tempo e Estudos Climáticos Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System. These environmental variables were used to adjust the multipollutant model for apparent temperature. To estimate association between hospitalizations owing to asthma and air pollutants, generalized additive Poisson regression models were developed, with lags as much as 5 days. There were 385 deaths with a daily mean (±SD) of 1.05±1.03 (range: 0-5). Exposure to NOx was significantly associated with mortality owing to respiratory diseases: relative risk (RR)=1.035 (95% confidence interval [CI]: 1.008-1.063) for lag 2, RR=1.064 (95%CI: 1.017-1.112) lag 3, RR=1.055 (95%CI: 1.025-1.085) lag 4, and RR=1.042 (95%CI: 1.010-1.076) lag 5. A 3 µg/m3 reduction in NOx concentration resulted in a decrease of 10-18 percentage points in risk of death caused by respiratory diseases. Even at NOx concentrations below the acceptable standard, there is association with deaths caused by respiratory diseases.

Antioxidant activity of rosemary and oregano ethanol extracts in soybean oil under thermal oxidation

Four experiments were conducted to measure the antioxidant activity of ethanol extracts of rosemary and oregano compared with synthetic antioxidants such as TBHQ and BHA/BHT. The antioxidant activity was determined and results differed from those of the Oven test at 63º C. Peroxide values and absorptivities at 232 nm of soybean oil under Oven test were lower in treatments with 25, 50, 75, 100 and 200 mg.Kg-1 TBHQ than in treatments with 1000 mg.Kg-1 oregano extract (O), 500 mg.Kg-1 rosemary extract (R) and their mixture R+O. All the treatments were effective in controlling the thermal oxidation of oils; the natural extracts were as effective as BHA+BHT and less effective than TBHQ. The natural extracts were mixed with 25, 50, 75 and 100 mg.Kg-1 TBHQ and then added to the oil. No improvement in antioxidative properties was observed. The best antioxidant concentration could be determined from polynomial regression and quadratic equation from the experimental data.

Volatile profile of heated soybean oil treated with quercetin and chlorogenic acid

Changes in the profile of volatile compounds after the heating of refined soybean oil without adding antioxidants, and treated with quercetin and chlorogenic acid (5-CQA) were investigated by GC/FID, GC/MS, and GC/SNIFFING. The heating temperature of the oil sample was 20 °C for the first minute, and then it was increased up to 160 °C at the rate of 10 °C min-1. The final temperature was kept for 10 minutes. 19 volatiles were identified in the heated samples without antioxidants. Medium-chain carbonyls predominated in the volatile fraction, mainly 2-heptenal, 2,4-heptadienal and 2,4-decadienal. Around 11 to 15 volatile compounds were detected in the heated samples treated with 5-CQA and quercetin, respectively. 5-CQA was not very efficient in delaying the formation of oxidative volatile compounds. The samples quercetin presented lower proportion of carbonyls with C6-C9.. The GC peak area data were used as an approach to estimate the relative content of each volatile compound and indicate that the samples treated with quercetin (p < 0.05) had significantly lower values for, 1-pentanol, 2,4-heptadienal, and 2,4-decadienal compared with those without antioxidants and treated with 5-CQA. GC/SNIFFING analysis revealed a smaller odor perception in the samples treated with 5-CQA compared to those without antioxidants. No odor was perceived in the heated samples treated with quercetin. These results indicate greater effectiveness of quercetin in delaying the formation of oxidative volatile compounds in soybean oils subjected to mild heating conditions. Apparently, biopolyphenols used in the present work showed good oxidative stability since no new volatile compound was detected in the heated samples treated with them.

Detection and quantification of Roundup Ready® soybean residues in sausage samples by conventional and real-time PCR

The increasing presence of products derived from genetically modified (GM) plants in human and animal diets has led to the development of detection methods to distinguish biotechnology-derived foods from conventional ones. The conventional and real-time PCR have been used, respectively, to detect and quantify GM residues in highly processed foods. DNA extraction is a critical step during the analysis process. Some factors such as DNA degradation, matrix effects, and the presence of PCR inhibitors imply that a detection or quantification limit, established for a given method, is restricted to a matrix used during validation and cannot be projected to any other matrix outside the scope of the method. In Brazil, sausage samples were the main class of processed products in which Roundup Ready® (RR) soybean residues were detected. Thus, the validation of methodologies for the detection and quantification of those residues is absolutely necessary. Sausage samples were submitted to two different methods of DNA extraction: modified Wizard and the CTAB method. The yield and quality were compared for both methods. DNA samples were analyzed by conventional and real-time PCR for the detection and quantification of Roundup Ready® soybean in the samples. At least 200 ng of total sausage DNA was necessary for a reliable quantification. Reactions containing DNA amounts below this value led to large variations on the expected GM percentage value. In conventional PCR, the detection limit varied from 1.0 to 500 ng, depending on the GM soybean content in the sample. The precision, performance, and linearity were relatively high indicating that the method used for analysis was satisfactory.

Physical properties of structured lipids from lard and soybean oil produced by enzymatic interesterification

The main goal of the present research was to evaluate the physical properties of blends of lard and soybean oil modified by enzymatic interesterification catalyzed by two different commercial (microbial) lipases, viz. from Candida cylindracea (AY30TM) and from Mucor circinelloides (M10TM). Pure lard exhibited a softening point of ca. 31.8 °C before interesterification, and this value shifted towards 29.1 °C after interesterification by AY30 lipase and towards 28.8 °C after interesterification by M10 lipase The interesterified lard exhibited lower consistency after reaction with both lipases, and this decrease was more pronounced for the reaction catalyzed by M10 lipase. This result was most likely due to the sn-1,3-specificity of M10 lipase. Pure lard displayed a lower SFC after interesterification, and M10 lipase proved to be more effective than AY30 lipase. The non-interesterified lard had a SFC of 31.3% at 10 °C, which was reduced to 23.8 and 19.9% after interesterification with AY30 lipase and M10 lipase, respectively. The lard and soybean oil blends were affected by the enzymatic interesterification and dilution with soybean oil.