Assessing levels of uric acid and other cardiovascular markers in prehypertensive and hypertensive adults.

INTRODUCTION: Although some studies have reported the association between uric acid (UA) and hypertension, evidence on prehypertension is still lacking. Therefore, the objective of this study was to determine the levels of UA and other cardiovascular markers among prehypertensive and hypertensive patients and assess their risk for developing arterial hypertension. METHODS: 157 individuals were recruited: 67 normotensive, 23 pre-hypertensive and 67 hypertensive. Blood samples were collected to measure biochemical parameters and anthropometric measurements and blood pressure were evaluated. We calculated the product of lipid accumulation and the visceral adiposity index to assess cardiovascular risk. RESULTS: Our data showed an increase in UA levels in normotensives (4.9±1.3mg/dL), prehypertensives (5.2±1.3mg/dL) and hypertensives (5.9±1.6mg/dL) (p=0.004). We found a higher frequency of hyperuricemia in the hypertensive group (34.3%) than in the normotensive group (13.4%, p<0.05). Hypertensive volunteers had lower levels of HDL-C (p=0.004 and p=0.003) and higher body mass indexes (p<0.001 and p=0.007), glucose (p<0.001 and p=0.033), triglycerides (p=0.001 and p=0.005), visceral adiposity index (p<0.001 and p=0.002) and lipid accumulation product (p<0.001 and p=0.007) than normotensive and prehypertensive participants. We also observed that individuals with UA≥6.2mg/dL had an increased risk of hypertension of 4.77 (p=0.003) compared to individuals with levels≤4.3mg/dL. CONCLUSION: Our results showed that UA is associated with increased blood pressure and unfavorable changes in anthropometric and biochemical parameters, which represent risk factors for hypertension and cardiovascular diseases.

Na+/K+ carrier ionophore antibiotics valinomycin and monensin enhance the antibacterial activity of fluoride.

Fluoride is routinely used as a highly effective antibacterial agent that interferes with bacterial metabolism through fundamentally different mechanisms. One of the major bacterial evasion mechanisms against fluoride is the impermeability of cell envelope to the anion that limits its cellular uptake. Therefore, translating such compounds to clinical settings requires novel mechanisms to facilitate the uptake of membrane-impermeant molecules. Published data have indicated antibiotic synergy between fluoride and membrane destabilizing agents that induce strong fluoride toxicity in bacteria via enhancing the permeability of bacterial membranes to fluoride. Here, we report a similar mechanism of antibiotic synergy between fluoride and potassium ion carriers, valinomycin and monensin against Gram-positive bacteria, B. subtilis and S. aureus. Molecular dynamics simulations were performed to understand the effect of potassium on the binding affinity of fluoride to monensin and valinomycin. The trajectory results strongly indicated that the monensin molecules transport fluoride ions across the cell membrane via formation of ion-pair between the monensin-K+ complex and a fluoride. This study provides new insights to design novel compounds to enhance the uptake of small toxic anions via synergistic interactions and thus exert strong antibacterial activity against a wide variety of pathogens.

Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis: development, characterization, biocompatibility, and anti-toxoplasma activity.

Ocular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii . Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.

Effects of Talinum paniculatum (Jacq.) Gaertn. leaf extract on general toxicity and pubertal development of rats.

Talinum paniculatum (Jacq.) Gaertn. (Talinaceae), popularly known as "major gomes," is a Brazilian Cerrado plant used in traditional medicine and as a food source. Recent studies have demonstrated its diuretic effects. However, no studies have been performed on its effects on the reproductive system. Therefore, we aimed to investigate the effects of the ethanol-soluble fraction of T. paniculatum leaves (ESTP) on general toxicity and on the pubertal development of male and female Wistar rats. For this purpose, the uterotrophic and the pubertal assays were performed. In the uterotrophic test, female immature rats were treated for three consecutive days with 30, 100, or 300 mg/kg of ESTP. Uterus without luminal fluid was weighed and the relative weight calculated. For the pubertal assay, male and female immature rats were submitted to 30-day treatment with 30 or 300 mg/kg of ESTP. Clinical signs of toxicity, biochemical, and histopathological parameters were evaluated. ESTP treatment did not promote estrogenic effects in female rats. In the pubertal test, no daily signs of toxicity or weight loss were observed. Moreover, ESTP did not affect the onset of vaginal opening and preputial separation and did not cause significant changes in biochemical parameters as well as in organ weight and histopathological analyses of animals.

Artificial neural networks as auxiliary tools for the improvement of bean plant architecture.

Classification using a scale of visual notes is a strategy used to select erect bean plants in order to improve bean plant architectures. Use of morphological traits associated with the phenotypic expression of bean architecture in classification procedures may enhance selection. The objective of this study was to evaluate the potential of artificial neural networks (ANNs) as auxiliary tools in the improvement of bean plant architecture. Data from 19 lines were evaluated for 22 traits, in 2007 and 2009 winter crops. Hypocotyl diameter and plant height were selected for analysis through ANNs. For classification purposes, these lines were separated into two groups, determined by the plant architecture notes. The predictive ability of ANNs was evaluated according to two scenarios to predict the plant architecture - training with 2007 data and validating in 2009 data (scenario 1), and vice versa (scenario 2). For this, ANNs were trained and validated using data from replicates of the evaluated lines for hypocotyl diameter individually, or together with the mean height of plants in the plot. In each scenario, the use of data from replicates or line means was evaluated for prediction through previously trained and validated ANNs. In both scenarios, ANNs based on hypocotyl diameter and mean height of plants were superior, since the error rates obtained were lower than those obtained using hypocotyl diameter only. Lower apparent error rates were verified in both scenarios for prediction when data on the means of the evaluated traits were submitted to better trained and validated ANNs.

Cell cycle kinetics, apoptosis rates and gene expressions of MDR-1, TP53, BCL-2 and BAX in transmissible venereal tumour cells and their association with therapy response.

Transmissible venereal tumour (TVT) generally presents different degrees of aggressiveness, which makes them unresponsive to conventional treatment protocols. This implies a progressive alteration of their biological profile. This study aimed to evaluate the cytotoxicity, cell survival, apoptosis and cell cycle alterations in TVT cell cultures subjected to treatment with vincristine. Similarly, it assessed possible implications of MDR-1, TP53, BCL-2, and BAX gene expressions in eight TVT primary cultures for both resistance to chemotherapy and biological behaviour. When comparing TVT cells receiving vincristine to those untreated, a statistical difference related to increased cytotoxicity and decreased survival rates, and alterations in G1 and S cell cycle phases were found but without detectable differences in apoptosis. Increased MDR-1 gene expression was observed after treatment. The groups did not differ statistically in relation to the TP53, BAX and BCL-2 genes. Although preliminary, the findings suggest that such augmented expression is related to tumour malignancy and chemotherapy resistance.

Selection index using the graphical area applied to sugarcane breeding.

This study aimed to develop a multivariate selection index based on the graphical area of a polygon formed by standardized values, also known as radar chart. This methodology may be used to assist selection of superior genotypes in sugarcane breeding programs. Seven technological traits in 37 sugarcane genotypes were evaluated. An area index (AI) was constructed and the resulting polygon areas were used to rank genotypes under selection. In this study, we propose the use of restricted maximum likelihood to estimate genetic parameters and mixed model equations to predict genotypic and breeding values. The area of each polygon was calculated for phenotypic, genotypic, and estimated breeding values. Thereby, the genotypes with larger area can be selected based on a detailed a posteriori evaluation of the radar charts. The proposed AI can be adjusted based on the breeders' specific interests, it is perfectly useful in other crops, and may also be applied to studies on genotype-environment interactions. Moreover, AI is a powerful tool that can evaluate trait stability of genotypes based on slight differences in the area formed by each genotype. Hence, this method is easy to apply and shows great potential for use in sugarcane breeding programs as well as in other breeding programs.

Adsorption-desorption reactions of selenium (VI) in tropical cultivated and uncultivated soils under Cerrado biome.

Soil management may affect selenium (Se) adsorption capacity. This study investigated adsorption and desorption of Se (VI) in selected Brazilian soils from the Cerrado biome, an area of ever increasing importance for agriculture expansion in Brazil. Soil samples were collected from cultivated and uncultivated soils, comprising clayed and sandy soils. Following chemical and mineralogical characterization, soil samples were subjected to Se adsorption and desorption tests. Adsorption was evaluated after a 72-h reaction with increasing concentrations of Se (0-2000 µg L-1) added as Na2SeO4 in a NaCl electrolyte solution (pH 5.5; ionic strength 15 mmol L-1). Desorption, as well as distribution coefficients (Kd) for selenate were also assessed. Soil management affected Se adsorption capacity, i.e., Se adsorbed amounts were higher for uncultivated soils, when compared to cultivated ones. Such results were also supported by data of Kd and maximum adsorption capacity of Se. This fact was attributed mainly to the presence of greater amounts of competing anions, especially phosphate, in cultivated soils, due to fertilizer application. Phosphate may compete with selenate for adsorption sites, decreasing Se retention. For the same group of soils (cultivated and uncultivated), Se adsorption was greater in the clayed soils compared to sandy ones. Our results support the idea that adding Se (VI) to the soil is a good strategy to increase Se levels in food crops (agronomic biofortification), especially when crops are grown in soils that have been cultivated over the time due to their low Se adsorption capacity (high Se availability).

Evaluation of the efficiency of artificial neural networks for genetic value prediction.

Artificial neural networks have shown great potential when applied to breeding programs. In this study, we propose the use of artificial neural networks as a viable alternative to conventional prediction methods. We conduct a thorough evaluation of the efficiency of these networks with respect to the prediction of breeding values. Therefore, we considered eight simulated scenarios, and for the purpose of genetic value prediction, seven statistical parameters in addition to the phenotypic mean in a network designed as a multilayer perceptron. After an evaluation of different network configurations, the results demonstrated the superiority of neural networks compared to estimation procedures based on linear models, and indicated high predictive accuracy and network efficiency.

Cell growth on 3D microstructured surfaces.

Chinese Hamster Ovary (CHO) cell cultures were grown on surfaces lithographed with periodic 3D hexagonal microcavity array morphology. The range of microcavity size (inscribed circle diameter) was from 12 µm to 560 µm. CHO cells were grown also on flat surfaces. The characterization was performed with respect to cell growth density (number of nuclei per unit area) by fluorescence optical microscopy and evaluated by correlation function analysis. We found that optimum microcavity radius was 80 µm, concerning to the maximum cell growth density, being even greater than the growth density on a flat (unstructured) substrate of the same material. This finding can be important for optimization of biotechnological processes and devices.

Superiority of artificial neural networks for a genetic classification procedure.

The correct classification of individuals is extremely important for the preservation of genetic variability and for maximization of yield in breeding programs using phenotypic traits and genetic markers. The Fisher and Anderson discriminant functions are commonly used multivariate statistical techniques for these situations, which allow for the allocation of an initially unknown individual to predefined groups. However, for higher levels of similarity, such as those found in backcrossed populations, these methods have proven to be inefficient. Recently, much research has been devoted to developing a new paradigm of computing known as artificial neural networks (ANNs), which can be used to solve many statistical problems, including classification problems. The aim of this study was to evaluate the feasibility of ANNs as an evaluation technique of genetic diversity by comparing their performance with that of traditional methods. The discriminant functions were equally ineffective in discriminating the populations, with error rates of 23-82%, thereby preventing the correct discrimination of individuals between populations. The ANN was effective in classifying populations with low and high differentiation, such as those derived from a genetic design established from backcrosses, even in cases of low differentiation of the data sets. The ANN appears to be a promising technique to solve classification problems, since the number of individuals classified incorrectly by the ANN was always lower than that of the discriminant functions. We envisage the potential relevant application of this improved procedure in the genomic classification of markers to distinguish between breeds and accessions.

Natural and Semi synthetic Antimalarial Compounds: Emphasis on the Terpene Class.

Malaria is one of the most important tropical diseases since more than 40% of the world population is at risk. This disease is endemic to more than 100 nations and remains one of the main leading causes of death in children less than five years of age worldwide. Natural product-derived compounds have played a major role in drug discovery, often as prototypes to obtain more active semi synthetic derivatives. Antimalarial pharmacotherapy is a significant example of plant-derived medicines, such as quinine and artemisinin. This review highlights studies on terpenes and their semi synthetic derivatives from natural sources with antimalarial activity reported in the literature during eleven years (2002-2013). A total of 114 compounds are found among terpenes and their semi synthetic derivatives. Cytotoxicity of the compounds is also found in this review. Furthermore, the physicochemical properties of the terpenes addressed are discussed based on seven well established descriptors, which provide a useful source for the elaboration of a terpene library of antimalarial compounds.

Composition and evaluation of the antimicrobial activity of the essential oil of Senecio selloi Spreng DC / Composição e avaliação da atividade antimicrobiana do óleo essencial de Senecio selloi Spreng DC

The essential oil of the aerial parts of Senecio selloi Spreng. DC. was extracted by hydrodistillation and analyzed by GC/MS. Nineteen compounds were identified, representing 99.9% of the total. The main compounds were found to be sesquiterpene hydrocarbons (71.3%), most of them with a bisabolane skeleton (59.4%). The major constituent was α-zingiberene (54%), followed by monoterpene α-isolimonene (16%). The essential oil was also tested against two Gram-positive and two Gram-negative bacterial species, three yeasts, and an algae. From the strains assayed, only Bacillus subtilis ATCC 6633 showed susceptibility (MIC and MBC = 4400 µg/mL) to the essential oil.

O óleo essencial das partes aéreas de Senecio selloi Spreng DC. foi extraído por hidrodestilação e analisado por CG/EM. Dezenove constituintes foram identificados, representando 99,9% do total. Os principais compostos fornecidos foram sesquiterpenos hidrocarbonetos (71,3%), a maioria destes com esqueleto bisabolano (59,4%). O constituinte majoritário foi a-zingibereno (54%), seguido do monoterpeno a-isolimoneno (16%). O óleo essencial foi testado contra duas cepas Gram-positivas e duas Gram-negativas, três fungos e uma alga. De todas as linhagens testadas somente Bacillus subtilis ATCC 6633 mostrou suscetibilidade (CIM e CBM = 4400 µg/mL) para o óleo essencial.

Ozone toxicity and walking response of populations of Sitophilus zeamais (Coleoptera: Curculionidae).

Ozone is a recognized alternative to the fumigants methyl bromide and phosphine for the control of stored product insects. However, as with fumigants in general, the potential sublethal effects of ozone on targeted insect species may compromise its efficacy and has yet to be investigated. Here, we determined ozone toxicity of 30 field-collected populations of the maize weevil, Sitophilus zeamais (Coleoptera: Curculionidae), and assessed the walking response of adult insects from these populations to sublethal ozone exposure. Time-mortality toxicity to ozone at 50 ppm concentration in a continuous 2 liter/min flow indicated uniform susceptibility among the populations studied without any indication of ozone resistance (toxicity ratios [at LT50] > two-fold). In contrast, there was significant variation in walking activity among the maize weevil populations, which was not correlated with ozone susceptibility. This was not surprising because of the relatively uniform susceptibility to ozone among the maize weevil populations. Respiration rate affected ozone toxicity but not walking activity, whereas body mass was negatively correlated with walking activity but was not correlated with ozone toxicity. Based on our data, lower respiration rates may potentially lead to reduced ozone uptake whereas larger body mass limits walking activity. Ozone seems a promising alternative fumigant with low short-term risk of resistance development because of the high susceptibility and low variability of response to this compound. Furthermore, ozone reduces walking activity of S. zeamais that implies it likely reduces the chances of insects escaping exposure at the early stages of fumigation.

The role of the TP53 gene during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

The medium-term tongue carcinogenesis assay is a useful model for studying oral squamous cell carcinomas phase by phase. The aim of the present study was to investigate the expression of p53 by immunohistochemistry and examine the DNA sequence of exons 5, 6, 7, and 8 of Tp53 for mutations during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). A total of 30 male Wistar rats were treated with 4-nitroquinoline 1-oxide in their drinking water for 4, 12, and 20 weeks at a dose of 50 ppm. Ten animals were used as negative controls. No histopathological changes in the tongue epithelia were observed in the control group or in the treatment group after 4 weeks of 4NQO. Following 12 weeks of treatment, hyperplasia as well as epithelial dysplasia was found in both mild and moderate forms. At 20 weeks, moderate and/or severe oral dysplasia and squamous cell carcinoma of the tongue were found, and the majority of animals had squamous cell carcinoma. The levels of p53 protein were increased (p < 0.05) in pre-neoplastic lesions and in squamous cell carcinomas in some of the tumor cells in squamous cell carcinomas. No mutations were found in any of the exons that were evaluated after the 4-, 12-, or 20-week treatments. Taken together, our results suggest that p53 expression may be an important event in the malignant conversion, whereas Tp53 mutations are not involved in the multi-step tongue carcinogenesis of Wistar rats induced by 4NQO.

[Hodgkin's disease in a patient with sarcoidosis]. / Doença de Hodgkin num doente com sarcoidose.

We present the case of a 37 years old woman with mediastinal lymphadenopathy since the age of 13. At de age of 14, the patient presented a left cervical lymphadenopathy and the onset of episodic nodose erythema. One year later, histological examinations of an enlarged lymph node revealed sarcoidal granulomata. Corticotherapy was prescribed and the patient became asymptomatic. At the age of 31, the patient complained of asthenia and fever with left parotid tumefaction. Corticotherapy was therefore resumed with good response. Three years later, the patient presented left parotid tumefaction, left cervical lymphadenopathy and painful eye congestion. The patient was submitted to parotidectomy and lymphadenectomy. One month later, an ulceration with progressive enlargement developed in the surgical scar, and the patient suffered from asthenia, anorexia, weight loss, fever, nocturnal sweating and cervical and axillary lymphadenopathy. At Santa Maria Hospital, the patient's condition was diagnosed as Hodgkin's disease, mixed cellularity subtype, stage II Bb with local cutaneous involvement. The prescribed treatment was MOPP/ABV-8 cycles- and complete remission was achieved. The patient is still asymptomatic after a follow-up of 6 years. Cutaneous involvement in Hodgkin's disease is rare and generally associated with advanced disease and poor prognosis, facts that did not occur in this case. The differential diagnosis between sarcoidosis and sarcoid reaction in Hodgkin's disease, the accidental coexistence of both entities and the evolution of sarcoidosis into lymphoma are also discussed. The sarcoidosis immune defect may be the result of the same immune disorder. No relationships between sarcoidosis and cutaneous involvement in Hodgkin's disease were found in the literature.

[Aneurysm of the abdominal aorta. Is arterial hypertension a risk factor?]. / Aneurisma da aorta abdominal. Hipertensão arterial como factor de risco?

OBJECTIVE: the purpose of this study was to measure ecographically and ascertain the characteristics of the abdominal aorta in a sample of the male population over sixty years, and try to correlate the findings with some so-called "risk factors" most currently quoted in the medical press, such as arterial hypertension, diabetes mellitus, tobacco consumption and coronary or cerebrovascular diseases. MATERIAL AND METHODS: this is a preliminary note of the results obtained in the first forty patients in a prospective study (still ongoing). They were choose randomly from all those admitted to the general medicine ward of Medicine I Hosp. St. Maria or attended at the Medicine or Cardiology/Hypertension outpatient clinics at the same hospital. Pearson's linear correlation, Student's t test for not paired samples and chi-square tests were used to analyze the results. MEASUREMENTS AND MAIN RESULTS: the medium value obtained for the abdominal aorta diameter (daa) was 28.8 mm (SD. +/- 3.6). In this sample there was no correlation between the age and daa (r:0.03), nor any statistical difference (chi-square) in the daa between the subgroups creating regarding the existence of hypertension no hypertension, active smoking/no smoking habits, or the association of all these so-called risk factors added to diabetes as opposed to their absence (the number of patients is still insufficient to reach statistical significance). CONCLUSIONS: in this study no risk factor/marker of the aneurysm of the abdominal aorta was so far detected in a population of aged male patients, but in some groups (as in the association of multiple factors) the number of patients was insufficient to reach any significant statistical conclusion.

[Rheumatic fever--exacerbation or decline? Analysis of patients admitted to a medical service within a period of 20 years]. / Febre reumática--recrudescência ou declínio? Análise dos internamentos num serviço de medicina com intervalo de 20 anos.

The authors revised 116 clinical files of patients admitted to a Medicine ward with Rheumatic Fever in the years 1959-63 and 1979-83, in order to detect a possible recrudescence of the disease. The following parameters were analysed: age, sex, length of hospital stay, clinical manifestations, ancillary exams, therapeutics and evolution. It was found an impressive decline in the incidence of the disease (90 cases vs 26) and also a very significant decrease of the period of hospitalization in the recent group of patients (p less than 0.0005); Carditis and relapses of Rheumatic Fever were more frequent in the old group of patients.