Development of polymeric nanoparticles containing neuroprotective compounds of Hypericum perforatum

Tese de Doutoramento em Biologia das Plantas - MAP BIOPLANT

Effect of a simulated kilning regime on the profile and antioxidant activity of the free phenolic acids extracted from green malt

Free phenolic acids were extracted from a laboratory-produced sample of green malt. Aliquots of the phenolic acid extract were heated from 25 to 110°C over 27 h, representative of a commercial kilning regime. Samples were taken at regular intervals throughout heating and were assessed for changes in antioxidant activity by both the 2,2(prime)-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical-cation scavenging (ABTS(^•+)) and the ferric-reducing antioxidant potential (FRAP) assays. Changes in the profile of the phenolic acids of the extracts were determined by HPLC. Overall, there was a decrease in both antioxidant activity level and the level of phenolic acids, but as the temperature increased from 80 to 100°C, there was an increase in both the antioxidant activity level and the level of detected phenolic acids.

ON THE RADICAL OF A FREE MALCEV ALGEBRA

We prove that the prime radical rad M of the free Malcev algebra M of rank more than two over a field of characteristic not equal 2 coincides with the set of all universally Engelian elements of M. Moreover, let T(M) be the ideal of M consisting of all stable identities of the split simple 7-dimensional Malcev algebra M over F. It is proved that rad M = J(M) boolean AND T(M), where J(M) is the Jacobian ideal of M. Similar results were proved by I. Shestakov and E. Zelmanov for free alternative and free Jordan algebras.

Low-grade endometrial stromal sarcoma with inferior vena cava tumor thrombus and intracardiac extension: radical resection may improve recurrence free survival

BACKGROUND: Endometrial stromal sarcoma (ESS) represents 0.2% of all uterine malignancies. Based on the mitotic activity, a distinction is made between low and high-grade ESS. Although the overall five-year survival rate for low-grade ESS exceeds 80%, about 50% of the patients show tumor recurrence, mostly after a long latency period. Tumor invasion of the great vessels is extremely rare. We describe a patient with advanced low-grade ESS with tumor invasion of the infrarenal aorta and the inferior vena cava. The patient presented with a large tumor thrombus extending from the inferior vena cava into the right atrium. METHODS: Review of literature and identification of 19 patients, including our own case report, with advanced low-grade ESS with invasion of the great vessels and formation of an inferior vena cava tumor thrombus. RESULTS: All 19 patients presented with an abdominal tumor mass and a tumor thrombus protruding into the inferior vena cava. The tumor thrombus extended into the right heart cavities in nine patients reaching the right atrium in four, the right ventricle in three and the pulmonary artery in two patients. There were 5 patients with an advanced primary tumor and 14 patients with an advanced recurrent tumor. Seven patients presented with synchronous metastatic disease and six patients with a pelvic tumor infiltrating the bladder, the rectosigmoid colon or the infrarenal aorta. Mean age at surgery was 45.9+/-12.3 years (median 47, range 25-65 years). Tumor thrombectomy was accomplished by cavatomy or by right atriotomy after installation of a cardiopulmonary bypass. There was no peri-operative mortality and a very low morbidity. Radical tumor resections were achieved in 10 patients. The follow-up for these 10 patients was 2+/-1.3 years (median 2, range 0.3-4.5 years). Nine patients remained recurrence free whereas one patient suffered an asymptomatic local recurrence. CONCLUSIONS: Low-grade ESS is a rare angioinvasive tumor with a high recurrence rate. Resection of an inferior vena cava tumor thrombus, even with extension into the right heart cavities, can be performed safely. Extensive radical surgery is therefore justified in the treatment of advanced tumor manifestations of a low-grade ESS potentially improving recurrence free survival.

Análise química e atividades biológicas de Guatteria elliptica R. E. Fries (Annonaceae)

A espécie endêmica G. elliptica R. E. Fries não apresentava estudos fitoquímicos e biológicos detalhados na literatura. Assim, o objetivo desse trabalho foi avaliar a composição química e as propriedades biológicas dos óleos essenciais, extratos brutos, alcaloides totais, tortas, frações das tortas, amostras isoladas dessa espécie. O material vegetal foi coletado em Paranapiacaba (Santo André, SP, Brasil). O óleo essencial extraído das folhas por destilação à vapor apresentou um rendimento de 0,2%. A análise histológica das folhas encontrou óleo em células oleíferas localizadas no parênquima esponjoso. A composição do óleo (CG-EM) indicou espatulenol e óxido de cariofileno como compostos majoritários. Os alcaloides totais foram obtidos dos extratos brutos das folhas e dos galhos e analisados por CG-EM, identificando quatro aporfinas (nornuciferina, estefarina, corituberina e asimilobina) e duas protoberberinas (discretamina e caseadina). Os alcaloides totais foram fracionados em coluna cromatográfica ou por Extração em Fase Sólida e purificados por cromatografia em camada preparativa, originando duas amostras (Amostra 9 e 10). Na Amostra 9, foram identificados dois alcaloides aporfinicos nornuciferina e asimilobina (CG-EM e RMN-1H). Na Amostra 10, foram identificados (LC-EM/EM) cinco alcaloides aporfínicos (desidronantenina, glaunidina, liriodenina, N-óxido de oliverina e telikovina) e um alcaloide protoberberínico (caseadina). Caseadina, glaunidina, N-óxido de oliverina e telikovina não foram previamente identificados em Guatteria. Os resíduos dos extratos brutos livres de alcaloides foram fracionados pelo método de partição com solventes de polaridade crescente. Os extratos brutos e as frações acetato de etila e butanólicas de folhas e galhos apresentaram flavonoides (NP-PEG). Nos ensaios biológicos, a melhor atividade antioxidante (sequestro do radical DPPH) foi encontrada para a fração clorofórmica dos galhos (EC50=24,25±1,14 µg/mL) e a torta dos galhos (EC50=26,23±4,20 µg/mL). No ensaio antimicrobiano pelo método turbidimétrico a atividade mais importante foi obtida contra Staphylococcus aureus (ATCC 6538) para os alcaloides totais dos galhos (CIM/CBM=0,12±0,01/0,26 mg/mL) e das folhas (CIM/CBM=0,21±0,01/0,28 mg/mL), e fração hexânica das folhas (CIM/CBM=0,24±0,02/>1 mg/mL). Uma alta atividade antitumoral foi observada frente a células humanas de mama (MCF-7) para Amostra 10 (IC50=2,28±0,18 µg/mL), fração de acetato de etila das folhas (IC50=4,47±0,40 µg/mL), óleo essencial (IC50=7,01±0,23 µg/mL) e os alcaloides totais das folhas (IC50=9,32±0,36 µg/mL). Para as células de próstata (PC-3), foi encontrada atividade para a Amostra 10 (IC50=1,37±0,36 µg/mL) e o óleo essencial (IC50=5,32±0,35 µg/mL). A futura aplicação dos extratos e frações de G. elliptica como um agente antitumoral parece ser segura, pois mantiveram uma viabilidade celular maior do que 90% no ensaio de citotoxicidade com culturas de fibroblasto murino (BALB/c 3T3, ATCC CCL-163) nas concentrações onde a atividade antitumoral foi promissora (<30 µg/mL) contra MCF-7 e/ou PC-3.

Utilization of free and microencapsulated Rosmarinus oficinalis L. extracts as bioactives ingredientes for new functional foods developmen

Currently, many consumers search for food with functional characteristics beyond their nutritional properties. Thus, the concept of functional food becomes a hot topic, allowing the obtaining of health benefits, including disease prevention. In this context, plants are recognized as sources of a wide range of bioactives, mainly phenolic compounds. In particular, the Rosmarinus officina/is L., commonly referred as rosemary, has several phenolic compounds with different bioactive properties such as antioxidant, antiinflammatory and antimicrobial activities, among others [!]. Hence, this plant has great potential for incorporation into foods in order to confer bioactivity to the final products. However, it should be highlighted that the bioactive compounds if exposed to adverse environments, for example: light, moisture, extreme pH, storage, food processing conditions, can be degraded leading to the consequent loss of bioactivity [2]. The microencapsulation is an alternative to overcome this problematic of bioactive compounds, as also to ensure controlled release, or target deliver to a specific site [3]. In this work, lyophilized rosemary aqueous extract prepared by in:'usion was used as a functional ingredient for cottage cheeses, after proving that it possesses, both higher content in phenolic compounds and higher antioxidant activity, comparatively with the corresponding hydroethanolic extract. The rosemary aqueous extract revealed, for example, a DPPH scavenging activity with an EC50 value of 73.44±0.54j!g/mL and presented as main phenolic compound the caffeic acid dimer, commonly named as rosmarinic acid. For the functionalized cottage cheeses, a decrease of bioactivity was observed after seven days under storage in fridge, when the extracts were incorporated in its free form. Therefore, to preserve the antioxidant activity, the rosemary aqueous extract was efficiently microencapsulated by using an atomization/coagulation technique and alginate as the matrix material and thereafter incorporated into the cottage cheeses. The final microspheres showed a size, estimated by OM using a magnification of I OOx, ranging between 51.1 and 122.6 J!m and an encapsulation efficiency, estimated through an indirect method, approaching 100%. Overall, the introduction of both free and microencapsulated extracts did not change the nutritional value of cottage cheeses, providing bioactivity that was more preserved with microencapsulated extracts putting in evidence the importance of using microencapsulation to develop effective functional foods.

Barrier-free substitutional doping of graphene sheets with boron atoms: Ab initio calculations

Using ab initio methods, we propose a simple and effective way to substitutionally dope graphene sheets with boron. The method consists of selectively exposing each side of the graphene sheet to different elements. We first expose one side of the membrane to boron while the other side is exposed to nitrogen. Proceeding this way, the B atoms will be spontaneously incorporated into the graphene membrane without any activation barrier. In a second step, the system should be exposed to a H-rich environment, which will remove the CN radical from the layer and form HCN, leading to a perfect substitutional doping.

Free Phenolic Acids from the Seaweed Halimeda monile with Antioxidant Effect Protecting against Liver Injury

Phenolic compounds are found in seaweed species together with other Substances presenting antioxidant activity. The objective of this work was to evaluate the antioxidant activity of the free phenolic acids (FPA) fraction from the seaweed Halimeda monile, and its activity to protect the expression of hepatic enzymes in rats, under experimental CCI(4) injury. The antioxidant activity was measured by the DPPH method. The FPA fraction (80 mg/kg, p.o.) was administered during 20 consecutive days to rats. The peroxidation was performed by thiobarbituric acid reactive substances (TBARS). The SOD and CAT enzymatic expressions were measured by RT/PCR. The histology technique was used to evaluate liver injuries. The expression of both, CAT and SOD genes, was more preserved by FPA. Only partial injury could be observed by histology in the liver of rats receiving FPA as compared with the control group; and CCI(4) administration induced 60% more peroxidation as compared with the rats receiving FPA. These data suggest that FPA could modulate the antioxidant enzymes and oxidative status in the liver through protection against adverse effects induced by chemical agents.

Improved cardiac performance after ischemia in aged rats supplemented with vitamin E and alpha-lipoic acid

The purpose of these experiments was to examine the effects of dietary antioxidant supplementation with vitamin E (VE) and alpha -lipoic acid (alpha -LA) on biochemical and physiological responses to in vivo myocardial ischemia-reperfusion (I-R) in aged rats. Male Fischer-334 rats (18 mo old) were assigned to either 1) a control diet (CON) or 2) a VE and alpha -LA supplemented diet (ANTIOX). After a 14-wk feeding period, animals in each group underwent an in vivo I-R protocol (25 min of myocardial ischemia and 15 min of reperfusion). During reperfusion, peak arterial pressure was significantly higher (P < 0.05) in ANTIOX animals compared with CON diet animals. I-R resulted in a significant increase (P < 0.05) in myocardial lipid peroxidation in CON diet animals but not in ANTIOX animals. Compared with ANTIOX animals, heart homogenates from CON animals experienced significantly less (P < 0.05) oxidative damage when exposed to five different in vitro radical producing systems. These data indicate that dietary supplementation with VE and -LA protects the aged rat heart from I-R-induced lipid peroxidation by scavenging numerous reactive oxygen species. Importantly, this protection is associated with improved cardiac performance during reperfusion.

Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: What does it mean?

Purpose: The number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen. Methods: Patients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease. Results: Thirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P < 0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P = 0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P = 0.2), and both were significantly better than patients with ypN+ disease (30 percent; P < 0.001). Conclusions: Absence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality.

Influence of Modified Posterior Reconstruction of the Rhabdosphincter on Early Recovery of Continence and Anastomotic Leakage Rates after Robot-Assisted Radical Prostatectomy

Background: Posterior reconstruction (PR) of the rhabdosphincter has been previously described during retropubic radical prostatectomy, and shorter times to return of urinary continence were reported using this technical modification. This technique has also been applied during robot-assisted radical prostatectomy (RARP); however, contradictory results have been reported. Objective: We describe here a modified technique for PR of the rhabdosphincter during RARP and report its impact on early recovery of urinary continence and on cystographic leakage rates. Design, setting, and participants: We analyzed 803 consecutive patients who underwent RARP by a single surgeon over a 12-mo period: 330 without performing PR and 473 with PR. Surgical procedure: The reconstruction was performed using two 6-in 3-0 Poliglecaprone sutures tied together. The free edge of the remaining Denonvillier`s fascia was identified after prostatectomy and approximated to the posterior aspect of the rhabdosphincter and the posterior median raphe using one arm of the continuous suture. The second layer of the reconstruction was then performed with the other arm of the suture, approximating the posterior lip of the bladder neck and vesicoprostatic muscle to the posterior urethral edge. Measurements: Continence rates were assessed with a self-administrated, validated questionnaire (Expanded Prostate Cancer Index Composite) at 1, 4, 12, and 24 wk after catheter removal. Continence was defined as the use of ""no absorbent pads."" Cystogram was performed in all patients on postoperative day 4 or 5 before catheter removal. Results and limitations: There was no significant difference between the groups with respect to patient age, body mass index, prostate-specific antigen levels, prostate weight, American Urological Association symptom score, estimated blood loss, operative time, number of nerve-sparing procedures, and days with catheter. In the PR group, the continence rates at 1, 4, 12, and 24 wk postoperatively were 22.7%, 42.7%, 91.8%, and 96.3%, respectively; in the non-PR group, the continence rates were 28.7%, 51.6%, 91.1%, and 97%, respectively. The modified PR technique resulted in significantly higher continence rates at 1 and 4 wk after catheter removal (p = 0.048 and 0.016, respectively), although the continence rates at 12 and 24 wk were not significantly affected (p = 0.908 and p = 0.741, respectively). The median interval to recovery of continence was also statistically significantly shorter in the PR group (median: 4 wk; 95% confidence interval [CI]: 3.39-4.61) when compared to the non-PR group (median: 6 wk; 95% CI: 5.18-6.82; log-rank test, p = 0.037). Finally, the incidence of cystographic leaks was lower in the PR group (0.4% vs 2.1%; p = 0.036). Although the patients` baseline characteristics were similar between the groups, the patients were not preoperatively randomized and unknown confounding factors may have influenced the results. Conclusions: Our modified PR combines the benefits of early recovery of continence reported with the original PR technique with a reinforced watertight closure of the posterior anastomotic wall. Shorter interval to recovery of continence and lower incidence of cystographic leaks were demonstrated with our PR technique when compared to RARP with no reconstruction. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.