Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites.

Introduction: Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Aß) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses. Methods: We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Aß-mediated neurotoxicities in AD.  Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD. Results: In response to various stimuli (e.g., infection, trauma, ischemia, air pollution, depression), Aß is released as an early responder immunopeptide triggering an innate immunity cascade in which Aß exhibits both immunomodulatory and antimicrobial properties (whether bacteria are present, or not), resulting in a misdirected attack upon "self" neurons, arising from analogous electronegative surface topologies between neurons and bacteria, and rendering them similarly susceptible to membrane-penetrating attack by antimicrobial peptides (AMPs) such as Aß. After this self-attack, the resulting necrotic (but not apoptotic) neuronal breakdown products diffuse to adjacent neurons eliciting further release of Aß, leading to a chronic self-perpetuating autoimmune cycle.  AD thus emerges as a brain-centric autoimmune disorder of innate immunity. Based upon the hypothesis that autoimmune processes are susceptible to endogenous regulatory processes, a subsequent comprehensive screening program of 1137 small molecules normally present in human brain identified tryptophan metabolism as a regulator of brain innate immunity and a source of potential endogenous anti-AD molecules capable of chemical modification into multi-site therapeutic modulators targeting AD's complex immunopathic-proteopathic pathogenesis. Discussion:  Conceptualizing AD as an autoimmune disease, identifying endogenous regulators of this autoimmunity, and designing small molecule drug-like analogues of these endogenous regulators represents a novel therapeutic approach for AD.

Ferulic acid amide derivatives with varying inhibition of amyloid-ß oligomerization and fibrillization.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized, in part, by the misfolding, oligomerization and fibrillization of amyloid-ß (Aß). Evidence suggests that the mechanisms underpinning Aß oligomerization and subsequent fibrillization are distinct, and may therefore require equally distinct therapeutic approaches. Prior studies have suggested that amide derivatives of ferulic acid, a natural polyphenol, may combat multiple AD pathologies, though its impact on Aß aggregation is controversial. We designed and synthesized a systematic library of amide derivatives of ferulic acid and evaluated their anti-oligomeric and anti-fibrillary capacities independently. Azetidine tethered, triphenyl derivatives were the most potent anti-oligomeric agents (compound 2i: IC50 = 1.8 µM ± 0.73 µM); notably these were only modest anti-fibrillary agents (20.57% inhibition of fibrillization), and exemplify the poor correlation between anti-oligomeric/fibrillary activities. These data were subsequently codified in an in silico QSAR model, which yielded a strong predictive model of anti-Aß oligomeric activity (κ = 0.919 for test set; κ = 0.737 for validation set).

O tratamento compensatório da Classe II e mordida aberta esquelética com bráquetes autoligados ­ relato de caso / Compensatory treatment of Class II and skeletal open bite with selfligating brackets ­ case report

Resumo A maloclusão de Classe II pode ser de origem dentária, esquelética ou a combinação de ambas e está presente em aproximadamente 60% dos pacientes que procuram tratamento ortodôntico corretivo. Paciente Padrão II facial necessita muitas vezes de descompensação dentária associada à cirurgia ortognática para correção das bases ósseas. Com o uso cada vez mais frequente do sistema autoligado na Ortodontia, o número de pacientes que tiveram indicação de extração como parte do seu tratamento diminuiu consideravelmente. O tratamento compensatório tem como objetivo minimizar com movimentos dento-alveolares as deformidades esqueléticas presentes. Este trabalho relata através de caso clínico, a eficiência do sistema autoligado em paciente Padrão II, sem extrações, com metas terapêuticas expansionistas em associação ao uso de elásticos de Classe II. Devido à rejeição do paciente à cirurgia ortognática, o tratamento compensatório resultou na camuflagem das discrepâncias esqueléticas através do sistema autoligado. Apesar da indicação cirúrgica, o tratamento compensatório apresentou movimentações dentárias significativas, resultando em sucesso do tratamento com considerável melhora facial. (AU)

Abstract Class II malocclusion can be dental, skeletal or a combination of both and is present in approximately 60% of patients seeking corrective orthodontic treatment. Facial Pattern II patient often needs dental decompensation associated with orthognathic surgery to correct the bone bases. With the increasing use of the self-ligating system in Orthodontics, the number of patients who were indicated for extraction as part of their treatment has decreased considerably. Compensatory treatment aims to minimize skeletal deformities with dento-alveolar movements. This paper reports through a clinical case, the efficiency of the self-ligating system in Pattern II patient without extractions with expansionist therapeutic goals in association with the use of Class II elastics. Due to the patient's rejection of orthognathic surgery, the compensatory treatment resulted in the camouflage of the skeletal discrepancies through the self-ligating system. Despite the surgical indication, the compensatory treatment presented significant dental movements, resulting in treatment success with considerable facial improvement (AU)

Nisin and acid resistance in Salmonella is enhanced by N-dodecanoyl-homoserine lactone.

Salmonella is a foodborne pathogen that can develop resistance to different stresses, which is essential for successful infection of the host. Some genes directly related to acid resistance are also involved in cationic peptide resistance in Gram-negative bacteria and could be under the control of quorum sensing (QS) mediated by autoinducer 1, known as acyl-homoserine lactone. Here, we investigated the influence of autoinducer 1, N-dodecanoyl-homoserine lactone (C12-HSL) on the resistance of Salmonella enterica subspecies enterica serovar Enteritidis to nisin and acid stress. Salmonella cells growing in anaerobic tryptic soy agar (TSB) at a pH of 7.0 for 7 h were submitted to acid stress at a pH of 4.5 in the presence and absence of nisin and were either supplemented or not with C12-HSL. Viable cell counts, gene expression, membrane charge alterations, fatty acid composition, and intracellular content leakage were observed. The autoinducer C12-HSL increased nisin resistance and survival at a pH of 4.5 in Salmonella. Also, C12-HSL increased the expression of the genes, phoP, phoQ, pmrA, and pmrB, which are involved with antimicrobial and acid resistance. The positive charge on the cell surface and concentration of cyclopropane fatty acid of the cellular membrane were increased in the presence of C12-HSL under acidic conditions, whereas membrane fluidity decreased. The loss of K+ and NADPH, promoted by nisin, was reduced in the presence of C12-HSL at a pH of 4.5. Taken together, these findings suggest that quorum sensing plays an important role in enhanced nisin and acid resistance in Salmonella.

The hidden variables problem in Alzheimer's disease clinical trial design.

As the leading cause of dementia worldwide, Alzheimer's disease has garnered intense academic and clinical interest. Yet, trials in search of a disease-modifying therapy have failed overwhelmingly. We suggest that, in part, this may be attributable to the influence of disruptive variables inherent to the framework of a clinical trial. Specifically, we observe that everyday factors such as diet, education, mental exertion, leisure participation, multilingualism, sleep, trauma, and physical activity, as well as clinical/study parameters including environment, family coaching, concurrent medications, and illnesses may serve as potent confounders, disruptors, or sources of bias to an otherwise significant drug-disease interaction. This perspective briefly summarizes the potential influence of these hidden variables on the outcomes of clinical trials and suggests strategies to abate their impact.

Topically applied linoleic/linolenic acid for chronic migraine.

The topical application of linoleic and linolenic acids is a potential prophylactic approach to migraine via an anti-inflammatory mechanism. We present a 45-year-old woman with chronic migraine without aura. Previous use of abortive or prophylactic therapies including sumatriptan, amitriptyline and topiramate had failed due to lack of efficacy or side-effects, especially vomiting. In search of a topical agent she performed an n-of-1 trial comparing application of linoleic acid (safflower oil) versus oleic acid (olive oil) for migraine relief. She found safflower oil to be effective. Topically applied safflower oil rich in linoleic and linolenic acids may offer a safe, easily applied, well-tolerated, effective anti-inflammatory approach for the prophylactic treatment of chronic migraine.

Mesenchymal stem cells in osteotomy repair after tibial tuberosity advancement in dogs with cranial cruciate ligament injury.

BACKGROUND: The cranial cruciate ligament rupture (CCLR) is the most commonly encountered orthopedic condition in dogs. Among the various techniques to treat this condition, tibial tuberosity advancement (TTA) has been used to obtain rapid recovery of the affected knee. The objective of this study was to evaluate the viability of the use of mesenchymal stem cells (MSC) implanted in the osteotomy site obtained by TTA in nine dogs diagnosed with CCLR. METHODS: The MSC were isolated from the adipose tissue of the dogs and cultured for eight days, the animals were divided into two groups. Animals from the treated group (GT) received cell transport medium containing about 1.5 millions MSC, and the animals from the control group (GC) received only the cell transport medium. The study was performed in a double-blind manner using radiographs acquired on days 15, 30, 60 and 120 after the procedure. Evaluations of the density of the trabecular bone were performed using image analysis software. The results were subjected to descriptive statistical analysis, followed by the normality test, Chi-square test, Mann-Whitney test and Tukey's multiple comparison test for p ≤ 0.05. RESULTS: After 30 days of the procedure, the animals of the GT presented an ossification mean 36.45% greater (p ≤ 0.033) than the GC, and there were no statistical differences for the other periods. CONCLUSIONS: Despite the total bone ossification within the expected period, there was no minimization of the estimated recovery time with the application of MSC, and inflammatory factors should be considered for reassessment of the therapeutic intervention time.

A selective volatilization method for determination of chloride and sulfate in calcium carbonate pharmaceutical raw material and commercial tablets.

In this work a feasible method for chloride and sulfate determination in calcium carbonate pharmaceutical raw material and commercial tablets by ion chromatography after microwave-induced combustion was developed. The analytes were released from matrix by combustion in closed system pressurized with oxygen. Starch as volatilization aid, 100mmolL-1 HNO3 as absorbing solution and 5min of microwave irradiation time were used. Recovery tests using standard solutions were performed for the accuracy evaluation. A mixture of calcium carbonate pharmaceutical raw material or commercial tablets, starch and a certified reference material was also used as a type of recovery test. Recoveries ranging from 88% to 103% were obtained in both spike tests. Limits of detection (Cl-: 40µgg-1 and SO42-: 140µgg-1) were up to eighteen times lower than the maximum limits established for the analytes by Brazilian, British, European and Indian Pharmacopoeias. The limit tests recommended by the European Pharmacopoeia for Cl- and SO42- in CaCO3 were carried out to compare the results. Chloride and SO42- concentrations in the samples analyzed by proposed method were in agreement with those results obtained using the tests recommended by the European Pharmacopoeia. However, the proposed method presents several advantages for the routine analysis when compared to pharmacopoeial methods, such as the quantitative simultaneous determination, high sample preparation throughput (up to eight samples per run in less than 30min), reduced volume of reagents and waste generation. Thus, the proposed method is indicated as an excellent alternative for Cl- and SO42- determination in CaCO3 pharmaceutical raw material and commercial tablets.

Analysis of polyphenols in brewer's spent grain and its comparison with corn silage and cereal brans commonly used for animal nutrition.

Brewer's spent grain (BSG) could be tested as an alternative source of polyphenols in animal nutrition. Proper extraction and analytical methods are critical for quantification. Thus, extraction for BSG, corn silage, and brans of rice, corn, and wheat were studied for the highest yield of polyphenols. A method for 18 phenolic monomers by HPLC-DAD was developed, validated, and applied to samples. An aqueous solution of NaOH (0.75% w/v) using integral samples for extraction resulted in the highest values for colorimetric measurements in all analyzed sources. Method by maceration showed the highest phenolic yield when applied in corn silage and BSG. However, for brans the best method was microwave assisted. Results from HPLC-DAD analysis clearly showed that native structures of phenolic compounds were simplified to its monomers allowing quantification and sample discrimination. BSG had the highest concentration of polyphenols and could be a promising and innovative source for animal feed studies.

Comparative study of intraperitoneal adhesions related to light-weight polypropylene mesh and type I polymerized and purified bovine collagen coated light-weight polypropylene mesh in rabbits.

PURPOSE: To compare the effectiveness of light-weight polypropylene mesh coated with polymerized and purified bovine type I collagen (Surgidry HNB) in the treatment of abdominal wall defect and the degree of adhesion formation. METHODS: Two types of polypropylene mesh were implanted after creation of defect measuring 6.0cm X 5.5cm in the anterior abdominal wall of 32 male New Zealand breed rabbits, divided in two groups (n = 32): (1) light-weigh macroporous polypropylene, (2) type I polymerized and purified bovine collagen coated light-weigh macroporous polypropylene. These animals were further accessed for adhesions, histological evaluation of inflammation and wall's thickness. RESULTS: The percentage of the area adhered in group 1 (62.31 ± 16.6) was higher compared to group 2 (22.19 ± 14.57) (p <0.05). There was an association between the percentage of the covered area by adhesions and the type of adhesion, toughness and the scores obtained by the adhesion score by correlation analysis (p <0.05). There was no difference between the groups in any variables in relation to the degree of inflammation. CONCLUSION: The purified type I bovine collagen coated light-weigh polypropylene mesh showed to be effective in the repair of abdominal wall defects and reducing adhesion formation.

Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response.

BACKGROUND: The Micro-Exon Gene-14 (MEG-14) displays a remarkable structure that allows the generation of antigenic variation in Schistosomes. Previous studies showed that the soluble portion of the MEG-14 protein displays features of an intrinsically disordered protein and is expressed exclusively in the parasite esophageal gland. These features indicated a potential for interaction with host proteins present in the plasma and cells from ingested blood. METHODS: A yeast two-hybrid experiment using as bait the soluble domain of Schistosoma mansoni MEG-14 (sMEG-14) against a human leukocyte cDNA library was performed. Pull-down and surface plasmon resonance (SPR) experiments were used to validate the interaction between sMEG-14 and human S100A9. Synchrotron radiation circular dichroism (SRCD) were used to detect structural changes upon interaction between sMEG-14 and human S100A9. Feeding of live parasites with S100A9 attached to a fluorophore allowed the tracking of the fate of this protein in the parasite digestive system. RESULTS: S100A9 interacted with sMEG-14 consistently in yeast two-hybrid assay, pull-down and SPR experiments. SRCD suggested that MEG-14 acquired a more regular structure as a result of the interaction with S100A9. Accumulation of recombinant S100A9 in the parasite's esophageal gland, when ingested by live worms suggests that such interaction may occur in vivo. CONCLUSION: S100A9, a protein previously described to be involved in modulation of inflammatory response, was found to interact with sMEG-14. GENERAL SIGNIFICANCE: Our results allow proposing a mechanism involving MEG-14 for the parasite to block inflammatory signaling, which would occur upon release of S100A9 when ingested blood cells are lysed.

Múltiplos pilomatricomas em membros superiores: relato de exérese cirúrgica / Multiple pilomatricomas in upper limbs: report of surgical exeresis

Pilomatricoma é uma neoplasia folicular benigna relativamente rara. Pode ocorrer em qualquer idade, mas menos de 13% dos casos acontecem em pessoas com mais de 50 anos, sendo mais comum em mulheres (1,5 a 2,5 mulheres:1 homem). A localização mais frequente é a região cervical, seguida das áreas frontais, periorbitárias e pré-auriculares (1). Clinicamente, apresenta-se como um tumor subcutâneo ou intradérmico, endurecido e de crescimento lento. O diagnóstico pré-cirúrgico é quase sempre difícil (3). O tratamento padrão é o cirúrgico, com margens de segurança amplas para minimizar o risco de recorrência nas variantes malignas (2,3). Relatamos um caso atípico e exuberante de múltiplos pilomatricomas em membros superiores em um paciente do sexo masculino de 55 anos (AU)

Pilomatricoma is a relatively rare benign follicular neoplasm. It can occur at any age, but less than 13% of cases occur in people over 50 years old, and it is more common in women (1.5 to 2.5 women: 1 man). The most frequent location is the cervical region, followed by the frontal, periorbital and pre-auricular areas (1). Clinically it presents as a hardened and slowly growing subcutaneous or intradermal tumor. Preoperative diagnosis is almost always difficult (3). The standard treatment is surgical, with wide safety margins to minimize the risk of recurrence in malignant variants (2,3). We report an atypical and exuberant case of multiple pilomatricomas in upper limbs in a 55-year-old male patient (AU)

Treatment of abdominal wall hernia with suture, or polypropylene, or collagen prosthesis.

PURPOSE: To develop an experimental model for incisional hernias and to compare morphological and functional aspects of hernia repairs by suture, polypropylene mesh and collagen mesh. METHODS: A defect measuring 7cm x 2cm was created in the anterior abdominal of 28 New Zealand male rabbits, divided into four groups (n = 7): (1) control, (2) suture of the anterior sheath of the rectus abdominal muscle, (3) setting of polypropylene mesh, and (4) setting of collagen mesh. On the 90th postoperative day, the animals were examined to verify the presence of incisional hernia. Samples of abdominal wall and scar were collected for histological study. RESULTS: Incisional hernia was identified in 85.7% of the control group, 57.1% of the suture group, 42.9% of the collagen mesh group, and none in the polypropylene mesh group (p = 0.015). Mesh exposure could be identified in 71.4% of the animals in group 3 and in no animal in group 4 (p = 0.021). The polypropylene mesh is effective in the treatment of abdominal wall defects, causing an intense inflammatory reaction. CONCLUSION: The collagen mesh is biocompatible, producing a minimal inflammatory reaction, but fails in the treatment of abdominal wall defects.

Selenium and mercury levels in rat liver slices co-treated with diphenyl diselenide and methylmercury.

Organoseleno-compounds have been investigated for its beneficial effects against methylmercury toxicity. In this way, diphenyl diselenide (PhSe)2 was demonstrated to decrease Hg accumulation in mice, protect against MeHg-induced mitochondrial dysfunction, and protect against the overall toxicity of this metal. In the present study we aimed to investigate if co-treatment with (PhSe)2 and MeHg could decrease accumulation of Hg in liver slices of rats. Rat liver slices were co-treated with (PhSe)2 (0.5; 5 µM) and/or MeHg (25 µM) for 30 min at 37 °C and Se and Hg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in the slices homogenate, P1 fraction, mitochondria and incubation medium. Co-treatment with (PhSe)2 and MeHg did not significantly alter Se levels in any of the samples when compared with compounds alone. In addition, co-treatment with (PhSe)2 and MeHg did not decrease Hg levels in any of the samples tested, although, co-incubation significantly increased Hg levels in homogenate. We suggest here that (PhSe)2 could exert its previously demonstrated protective effects not by reducing MeHg levels, but forming a complex with MeHg avoiding it to bind to critical molecules in cell.

Relato de caso: pólipo piloso da nasofaringe em adulto / Case report: a hairy polyp of nasopharynx in adult

O pólipo piloso é um tumor congênito que se manifesta, normalmente, nos primeiros anos de vida, como uma massa coberta com pele contendo glândula sebácea e pelo. Foi descrito, primeiramente, por Brown-Kelly em 1918, com predominância no sexo feminino. A manifestação clínica depende da localização e do tamanho do pólipo, mas, geralmente, causa sintomas respiratórios e alimentares. Há predileção pelo lado esquerdo do organismo, ainda não explicada (1). Não há predisposição genética ou identificação em parentes, e normalmente apresenta-se como um defeito isolado, sem relatos de malignização. O diagnóstico pode ser suspeitado através do estudo de imagem. O tratamento envolve a exérese completa da massa, não havendo necessidade de nenhuma outra complementação (2). Relatamos o caso de uma paciente de 21 anos cujo diagnóstico foi confirmado com anatomopatológico da peça cirúrgica(AU)

The hairy polyp is a congenital tumor that usually manifests in early life as a mass covered with skin containing sebaceous gland and hair. It was first described by Brown-Kelly in 1918, predominantly in females. The clinical manifestation depends on the polyp's location and size, but it usually causes respiratory and feeding symptoms. It is more likely to appear on the left side of the body, a predilection not yet explained. (1) There is no genetic predisposition or identification in relatives, and it usually presents as an isolated defect without malignant reports. The diagnosis may be suspected by imaging. Treatment involves complete excision of the mass, with no need for any other action. (2) We report the case of a 21-year-old patient whose diagnosis was confirmed by pathology of the surgical specimen(AU)

Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats.

The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.

Microwave-assisted diluted acid digestion for trace elements analysis of edible soybean products.

A new method for the decomposition of soybean based edible products (soy extract, textured soy protein, transgenic soybeans, and whole soy flour) was developed to essential (Co, Cr, Cu, Fe, Mn, Ni, Se, V, and Zn) and non-essential (As, Ba, Cd, Pb, and Sr) trace elements determination by ICP OES and ICP-MS respectively. Effects related to the concentration of HNO3 (2.1-14.5 mol L(-1)) and the use of hydrogen peroxide on the efficiency of decomposition was evaluated based on the residual carbon content (RCC). It was demonstrated that 2.1 mol L(-1) HNO3 plus 1.0 mL H2O2 was suitable for an efficient digestion, since RCC was lower than 18% and the agreement with certified values and spike recoveries were higher than 90% for all analytes. The concentrations of analytes in the samples (minimum-maximum in mgkg(-1)) were: The concentrations of analytes in the samples (minimum-maximum in mgkg(-1)) were: As (<0.007-0.040), Ba (0.064-10.6), Cd (<0.006-0.028), Co (0.012-102), Cr (0.56-5.88), Cu (6.53-13.9), Fe (24.9-126), Mn (16.4-35.2), Ni (0.74-4.78), Se (<2.90-25), Sr (2.48-20.1), Pb (<0.029-0.11), V (<0.027-20), and Zn (30.1-47.3). Soy-based foods investigated in this study presented variable composition in terms of essential and potentially toxic elements, which can be attributed to different methods of processing.

Caracterização, teor de polifenóis totais e atividade antioxidante em diferentes tipos de erva-mate (Ilex paraguariensis St. Hill.) para chimarrão / Characterization and determination of the total polyphenols contents and the antioxidant activity in four types of yerba mate (Ilex paraguariensis St. Hill.) for preparing chimarrão

Considerando-se a ampla utilização das folhas da erva-mate, bem como os benefícios advindos de seu emprego, neste estudo foi avaliada a qualidade de quatro tipos de ervas-mate nativas de espécime chimarrão: tradicional, com adição de 5 % e 10 % de açúcar, e a moída grossa, bem como a homogeneidade em três lotes dos produtos, correspondentes a diferentes semanas de processamento. Foram avaliadas as propriedades físico-químicas, o teor de polifenóis totais e a atividade antioxidante. Os extratos aquosos de erva-mate foram elaborados a 85 ºC, mantidos em de cocção em sistema fechado durante 10 e 30 minutos.As ervas-mate com adição de açúcar apresentaram menores teores de material mineral e de fibra bruta quando comparadas aos tipos tradicional e moída grossa. A erva-mate moída grossa acondicionada em embalagem laminada apresentou os menores valores de atividade de água em relação aos outros tipos de ervas acondicionados em embalagem de papel. A embalagem laminada também contribuiu para a menor absorção de oxigênio, que retarda a oxidação da clorofila e mantém a coloração verde do produto.Os extratos elaborados a partir da erva-mate moída grossa e os que permaneceram por maior tempo em decocção apresentaram maiores teores de polifenóis totais...

Acute exposure to low lead levels and its implications on the activity and expression of cytosolic thioredoxin reductase in the kidney.

Renal thioredoxin reductase-1 (TrxR-1) activity is stimulated at lead doses lower than that necessary to inhibit δ-aminolevulinate dehydratase activity (δ-ALA-D), which is a classical early biomarker of lead effects. Thus, we hypothesized that the activity of TrxR-1 could be a more sensitive early indicator of lead effects than is δ-ALA-D. To evaluate this hypothesis, we assessed the blood and renal TrxR-1 activity and its gene expression along with biomarkers of oxidative damage, antioxidant enzyme activities and biomarkers of lead exposure in rats acutely exposed to lead. A histopathological analysis was performed to verify renal damage. The increase in renal TrxR-1 activity paralleled the increase in the blood and renal lead levels at 6, 24 and 48 hr after the exposure to 25 mg/kg lead acetate (p < 0.05), whereas its expression was increased 24 and 48 hr after exposure. These effects were not accompanied by oxidative or tissue damage in the kidneys. Blood TrxR-1 activity was not affected by lead exposure (up to 25 mg/kg). Erythrocyte δ-ALA-D activity was inhibited 6 hr after the exposure to 25 mg/kg lead acetate (p < 0.05) but recovered thereafter. Renal δ-ALA-D activity decreased 24 and 48 hr after the exposure to 25 mg/kg lead acetate. There were no changes in any parameters at lead acetate doses <25 mg/kg. Our results indicate that blood TrxR-1 activity is not a suitable indicator of lead effects. In contrast, the increase in renal TrxR-1 expression and activity is implicated in the early events of lead exposure, most likely as a protective cellular mechanism against lead toxicity.

Current perception threshold and reaction time in the assessment of sensory peripheral nerve fibers through sinusoidal electrical stimulation at different frequencies

INTRODUCTION: The Perception Sensory Threshold (ST) for sinusoidal current stimuli at 5, 250, and 2,000 Hz is commonly used in the assessment of peripheral nerve fibers (C, Aδ, and Aβ, respectively). However, the neuroselectivity of these frequencies is far from consensus. In addition, Reaction Time (RT) measurements suggest that 2,000 Hz stimuli excite Aβ-fibers, 250 Hz Aβ- or Aδ-fibers, as well as 5 Hz Aβ-, Aδ- or C-fibers. Therefore, we suppose that the sinusoidal current neuroselectivity may be better observed if ST and RT parameters are jointly evaluated. In addition, we have investigated whether there are other sets of frequencies that could be used. METHODS: Thus this work investigates ST and RT for stimuli with frequency ranging from 1 to 3,000 Hz, on 28 healthy subjects aged from 19 to 44 years old (27.1±5.49). ST and RT dissimilarity among different frequencies was evaluated applying bi-dimensional Fisher Quadratic Discriminant. RESULTS: The lowest classification error (3.6%) was obtained for 1, 250, and 3,000 Hz. Error for 5, 250, and 2,000Hz was 16.7%. Stimulation frequency at 1 Hz evoked more sensations related to C-fibers (53% of reports) than to Aβ-fibers (36%). However, this behavior did not repeat itself at 5 Hz (only 21% of perceptions were related to C-fibers against 64% to Aβ-fibers). Sensations related to Aβ-fibers prevailed for the highest frequencies presented to the subjects (2,000 Hz - 82% and 3,000 Hz - 93%). Mean RT values showed a decreasing trend with frequency. CONCLUSION: These results suggest that frequencies 1, 250, and 3,000 Hz are more neuroselective than 5, 250, and 2,000 Hz for the evaluation of peripheral sensitive fibers. Furthermore, they show RT usefulness.