Synthesis of the Macrolactone of Migrastatin and Analogues with Potent Cell-Migration Inhibitory Activity

The synthesis of the macrolactone core of migrastatin 2, its potent anti-metastasis analogue 34, and ester derivatives 35 and 38 are reported. The approach involves the use of a dihydroxylation reaction to establish the desired C-8 stereocenter followed by a metathesis cyclization reaction. The effects of the compounds on the migration and invasion of human breast cancer cells were evaluated by using the wound-healing and the Boyden-chamber cell-migration and cell-invasion assays. The results revealed a high potency of the macrolactones 2 and 34 and the ester analogues 35 and 38, which suggests they have potential as antimetastatic agents.

Histological evaluation of chitosan-based biomaterials used for the correction of critical size defects in rat`s calvaria

Chitosan, a biopolymer obtained from chitin, and its derivates, such as chitosan hydrochloride, has been reported as wound healing accelerators and as possible bone substitutes for tissue engineering, and therefore these Substances could be relevant in dentistry and periodontology. The purpose of this investigation was to make a histological evaluation of chitosan and chitosan hydrochloride biomaterials (gels) used in the correction of critical size bone defects made in rat`s calvaria. Bone defects of 8 mm in diameter were surgically created in the calviria of 50 Holtzman (Rattus norvegicus) rats and filled with blood clot (control), low molecular weight chitosan, high molecular weight chitosan, low molecular weight chitosan hydrochloride, and high molecular weight chitosan hydrochloride, numbering 10 animals, divided into two experimental periods (15 and 60 days), for each biomaterial. The histological evaluation was made based on the morphology of the new-formed tissues in defect`s region, and the results indicated that there was no statistical difference between the groups when the new bone formation in the entire defect`s area were compared (p > 0.05) and, except in the control groups, assorted degrees of inflammation Could be Seen. In Conclusion, chitosan and chitosan hydrochloride biomaterials used in this study were not able to promote new bone formation in critical size defects made in rat`s calvaria. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 107-114, 2016

Mutagênese induzida por flavonóides presentes do decocto das cascas da aroeira (Schinus terebinthifolius, Raddi)

The decoction of Brazilian pepper tree barks (Schinus terebinthifolius, Raddi), is used in medicine as wound healing and antiinflamatory. Once extracts from this plant are used for acceleration of scar s process, it is important to study their mutagenic and genotoxic potential. In previous works in our laboratory, it was observed mutagenicity caused by the decoction when in high concentrations. Among the chemical compounds of this plant that could be able to induce mutation, the flavonoids were the only group that was referred to have either an oxidant or antioxidant potential. The flavonoids were isolated, purified and quantified by adsorptive column chromatography under silica gel, bacterial and in vitro genotoxic tests were realized to determine if the flavonoids were the responsible agents for this mutagenicity found. The tests realized with plasmidial DNA were indicative that the flavonoids are probably genotoxic, due to the presence of correlation between increase of the flavonoid concentration and in plasmidial DNA double strand breakage visualized in agarose gel, as well as they were capable to generated abasic sites shown by the in vitro treatment with exonuclease III. The same tests with plasmidial DNA in the presence of copper [10 µM] and of a Tris-HCl pH 7.5 [10 µM] buffer were realized with the isolated flavonoids to determine if there would be or not participation of reactive oxygen species (ROS). The transformation of plasmidial DNA in different bacterial strains proficient and deficient in DNA repair enzymes in the presence or not of a Tris-HCl buffer, suggests that the enzymes that repair oxidative lesions are necessary to repair the lesions generated by the flavonoids and that ROS are generated and are necessary to promote the lesions. Bacterial tests with Escherichia coli strains of the CC collection (deficient or not for DNA repair enzymes), showed that the flavonoids are able to increase the frequency of mutations, mainly in strains mutated in repair enzymes (MutM, MutY-glicosylases and double mutant), suggesting that these agents are responsible for the enhancement in the mutation rate. In order to determine the mutation spectrum caused by the flavonoids of the Brazilian pepper tree stem bark, plasmidial DNA previously treated with the flavonoids were transformed in bacterial strains deficient and proficient in the DNA repair enzymes, followed by a blue-white selection with X-gal, DNA amplification by PCR and sequencing the positive mutant clones. Analysis of the mutants obtained from strains CC104, CC104mutM, CC104mutY, CC104mutMmutY, BW9101, BW9109 indicated a predominance of some mutations like G:C to C:G that can be correlated with the origin of 8-oxoG, due to oxidative lesions caused by the flavonoids. So it can concluded that the flavonoid isolated or in fractions enriched on them are genotoxic and mutagenic, and their mutations are predominantly oxidative, mediated by ROS, and the lesions are recognized by the BER system. In this way it is proposed that the flavonoids can act in two different ways to generate the DNA lesion: 1. in a Fenton-like reaction, when the flavonoid are in the presence of metal ions and that together with the water generate ROS that promotes the DNA lesions; 2. in another way the lesions can be generated by the formation of ROS due to the internal chemical structure of the flavonoid molecule due to the quantity and location of hydroxyl groups, and so producing the DNA lesions, those lesions can be directly (suggested by the in vitro experiments) or indirectly done (supported by the experiments using the CC bacterial strains)

Anti-leishmanial effects of purified compounds from aerial parts of Baccharis uncinella C. DC. (Asteraceae)

Species of Baccharis exhibit antibiotic, antiseptic, wound-healing, and anti-protozoal properties, and have been used in the traditional medicine of South America for the treatment of several diseases. In the present work, the fractionation of EtOH extract from aerial parts of Baccharis uncinella indicated that the isolated compounds caffeic acid and pectolinaringenin showed inhibitory activity against Leishmania (L.) amazonensis and Leishmania (V.) braziliensis promastigotes, respectively. Moreover, amastigote forms of both species were highly sensible to the fraction composed by oleanolic + ursolic acids and pectolinaringenin. Caffeic acid also inhibited amastigote forms of L. (L.) amazonensis, but this effect was weak in L. (V.) braziliensis amastigotes. The treatment of infected macrophages with these compounds did not alter the levels of nitrates, indicating a direct effect of the compounds on amastigote stages. The results presented herein suggest that the active components from B. uncinella can be important to the design of new drugs against American tegumentar leishmaniases.

Evaluation of anti-inflammatory activity of derivatives from aerial parts of Baccharis uncinella

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efetividade da terapia fisica descongestiva na cicatrização de úlceras venosas

A venous ulcer is the most serious clinical manifestation of chronic venous failure, and the most frequent in lower limbs, accounting for 70% of all ulcers. Patients may suffer from this infirmity for several years without healing of the lesion if treatment is inadequate. The aim of this investigation was to verify the effectiveness of decongestive physical therapy in the healing of venous ulcers. This is a quasi-experimental, interventionist study, with paired, non-probabilistic sampling, composed of 50 patients divided into two groups: control and intervention, each composed of 25 patients. Both groups were identically treated for six months with daily dressings and the latter also underwent complex physical therapy consisting of a combination of the following techniques: manual lymphatic drainage, compression bandaging, lower limb elevation, myolymphokinetic exercises and skin care. The study was approved (Protocol no. 59/2007) by the Ethics Committee of the State University of Southeast Bahia. The Mann-Whitney and Chi-square tests were applied for data analysis. After statistical analysis the patients who underwent therapy showed a statistically significant difference with respect to wound contraction starting in the second month of treatment. Compared to the control, the intervention group showed a greater reduction in both pain and edema starting in the third and fourth month of therapy, respectively. To reinforce these findings, the mean percentage of tissue present at the base of the ulcer (granulation/fibrin ratio) was calculated. The intervention group showed greater granulation at the base of the ulcer compared to the control, significant from the second month of treatment on. It was observed in this study that lymphotherapy, when compared between the intervention and control groups, accelerated the healing process, and reduced pain and edema in the affected limbs. It is expected, therefore, that these results widen scientific knowledge and we suggest that this therapy be used 78 not only to reduce lymphedema, but also as a treatment option for venous ulcers, given its easy application and low cost. The data, therefore, demonstrated the importance of basic care on the part of a multiprofessional and transdisciplinary health team involved in the healing process of these infirmities, thereby contributing to better quality of life in these individuals

Effects of ethyl-cyanoacrylate and octyl-cyanoacrylate on experimental corneal lesions in rabbits

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Expression of matrix metalloproteinases, type IV collagen, and interleukin-10 in rabbits treated with morphine after lamellar keratectomy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morfometria de fibroblastos e fibrócitos durante o processo cicatricial na pele de coelhos da raça Nova Zelândia Branco tratados com calêndula

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Custo-efetividade da terapia compressiva no processo de cicatrização de úlceras venosas

Analytical study of therapeutic nonrandomized intervention type, intra-group controlled, with the aim of analyzing the cost-effectiveness of compression therapy with manipulated Unna boot in relation to conventional therapy in the healing of venous ulcers (VU) of patients treated in ambulatory clinic. The study population was composed by patients with VU treated by angiologists in Surgical Clinic Ambulatory of the Onofre Lopes University Hospital (HUOL) with a sample of 18 patients. It obtained the assent of the HUOL Ethics in Research Committee (Protocol 276/09). Data collection was performed over a period of four months by the own master's student and 34 nursing students, through the application of the research instrument in the admission of patients to the study and in the ten subsequent evaluations, performed at the time of changing Unna boot, weekly, for a maximum period of 10 weeks. The data were analyzed with SPSS 15.0 software, using descriptive and inferential statistics, and presented as tables, charts and graphs. Among those surveyed, prevailed: females, mean age 57.6 years, low education and income levels, most retired, unemployed or off work, with the standing position more than six hours per day and up to eight hours daily of domestic or occupational activities. In health status profile of respondents there were predominantly sleep, rest and inadequate elevation of the lower limbs, no smoking and/or alcohol use, presence of hypertension and no use of drugs. Most presented the first VU for over 10 years, recurrences, present VU for more than five years, involvement of left leg, in malleolar and / or distal leg region, mild edema, hyperpigmentation, lipodermatosclerosis, telangiectasies, reticular and varicose veins, mild pain, serous exudate in moderate quantity, small lesions (up to 50cm2), with predominance of granulation tissue and / or epithelialization and demarcated, elevated and irregular borders, with crusts and macerated. Most patients reported that in the 10 weeks prior to admission, made bandages at home and / or Basic Health Unit and / or ambulatory, with nursing aides or technicians, daily, and on weekends or holidays, performed by patients themselves, using healing ointment on the lesion, being observed granulation / epithelialization and increase in VU prevalent in the 10 weeks of traditional treatment. After follow up with manipulated Unna boot, was observed a decrease of lesions in all study patients, with complete healing in 27.8% of those between 1 and 5 weeks of treatment, with satisfactory evolution of the lesions, pain and ankle and calf circumferences, and unsatisfactory development of the borders of ulcers, edema, sleep, rest and elevation of the lower limbs, especially in more chronic patients. Furthermore, patients who achieved total healing and exhibited the greatest percentage reduction of lesions had a higher number of wound healing factors (ρ = 0.01 and ρ = 0.027, respectively). The manipulated Unna boot showed better results in those patients with shorter duration of injury, leading them to a satisfactory outcome within a short period of treatment. After the cost-effectiveness analysis, we conclude that the manipulated Unna boot is more effective than conventional therapy in the healing process of VU and is more cost-effective in patients with shorter lesions (ρ = 0.001), shorter treatment (ρ = 0.000) and greater number of wound healing factors (ρ = 0.005).

Validação de protocolo de assistência para pessoas com úlcera venosa na atenção primária

People with venous ulcers constitute as an important public health problem, its treatment is onerous and require assistance provided by trained professionals, systematized through protocols, however what lies in the assistance is that the management of this group of people differs from that preconized in the scientific literature, interfering with wound healing and quality of life of affected. In this sense, the construction of a assistance protocol specific to people with venous ulcers (VU) can help professionals of the Family Health Strategy both in patient assessment as and in establishment of quality assistance. Thus, this study aimed to analyse the validity of a multiprofessional assistance protocol for people with venous ulcers in primary care by health professionals using Delphi technique. This is a quantitative study, the methodological type conducted in two steps: first step related to integrative literature review to subsidize the development of the protocol, then these aspects were organized and proposed to the judges of the study through the Delphi technique. The study was initiated after approval by the Research Ethics Committee. The first step was performed between August and September 2012, in the virtual library of health, in the page of the Coordination of Improvement of Higher Education Personnel, of Municipal Health Secretariat and international guidelines of associations and in the subsequent step carried out between September 2012 to January 2013, was performed search by Lattes platform of the National Council of Technological and Scientific Development, in order to identify health professionals in Brazil who act as judges of the instrument and then, via online, the form was submitted to them.The sample for the second step was 51 judges in the first round and 35 for the second round Delphi. The analysis was done by adopting Kappa index ≥ 0.81 and Content Validity Index (CVI)> 0.80. In the first submission for the judges, items that did not reach Kappa and CVI established were: request / realization / test results, demographic data, medical history, risk factors, verification of pain / vital signs / pulse / infection signs / lesion location/ edema and pain treatment. After removal of items which have not obtained Kappa or CVI index established, it was found achieving optimal levels of these index for the categories. In the next step was the ressubmissão of protocol to judges through the Delphi technique in it was found that, of the 15 categories of the protocol, 12 presented higher scores in Delphi 2 phase and the other three categories remained the same Kappa and IVC of the previous phase. As for the average of evaluation requirements of the protocol was found that the scores assigned by the judges were higher in the second phase in nine of the 10 items, remaining the same in only one of the items indicating validity of the instrument before the consensus of the judges. Thus, we accepted the alternative hypothesis in this study, as they were obtained in the second Delphi phase the validity index greater than or equal to the Delphi 1 phase. The formulation of this assistance protocol valid and reproducible will enable a reorganization and redesign of assistance, with standardization of actions and continuity of care for persons with venous ulcers in primary health care

Evidências de validação de um protocolo para assistência às pessoas com úlceras venosas em serviços de alta complexidade

Venous ulcers are lesions resulting from chronic venous insufficiency, venous valvular abnormalities and venous thrombosis. Its occurrence has been growing with the increase in life expectancy of the world population. Considered as fundamental aspects in the approach to the person with venous ulcer care with the interdisciplinary approach, adoption of protocol-specific knowledge, technical skill, coordination between levels of care complexity of the Health System and active participation of patients and their families, a holistic perspective. The construction of a clinical protocol for people with venous ulcers can help professionals of high complexity services in patient assessment and the establishment of quality care in a systematic way and focused on the factors that interfere with wound healing. Thus, this study aimed to analyze the evidence of validation of a clinical protocol for people with venous ulcers treated at high-complexity services. This is a methodological study with a quantitative approach, developed in three stages: literature review, evidence of content validity and evidence of validation in the clinical context. Approved by the Federal University of Rio Grande do Norte Research Ethics Committee (Opinion: 147.452 and CAAE: 07556312.0.0000.5537). The literature review was conducted in August and September 2012, becoming the basis for the construction of the protocol. Then the evidence of content validity, which included 53 judges (experts) selected by the Lattes platform to evaluate the protocol items was performed. The judges were contacted by e-mail and rated the protocol via Google Docs . After analyzing the ratios obtained in this step, which reported kappa between 0.75 and 0.96 and between 0.80 and 0.98 IVC, and the suggestions of the judges, the protocol was adjusted and subjected to empirical evidence to validate the clinical setting at the University Hospital Onofre Lopes in Natal / RN. Evidence of validation in the clinical setting involved 4 judges who acted in pairs (paired) evaluated 32 patients with venous ulcers in the clinical context of high complexity. In both stages, we used the Kappa Index and Content Validity Index to analyze the responses of the judges. The parameters set as acceptable for these indices were: Kappa ≥ 0.61 and Content Validity Index > 0.80. Any evidence of content validity, as evidence of validation in the clinical context, the protocol items that have not reached Kappa and Content Validity Index established indices were excluded and some items were modified or added after suggestions. The process of content validation evidence and evidence of validation in the clinical setting allowed the improvement of the protocol for the care of people with venous ulcers initially proposed. The initial version of the protocol, built from the literature, contained 15 categories and 108 items; after evidence of content validity, remained the reduction to 15 categories with 91 items; the final version, clinically validated, is composed of the same 15 categories, 76 items. The protocol was validated in its content and in the clinical aspect, so we accepted the alternative hypothesis in the study. This protocol may contribute to the care system, allowing tailor behaviors and promote greater resolution in the treatment of people with venous ulcers in health services of high complexity

Integridade tissular de pacientes com úlceras venosas: um estudo baseado na Classificação dos Resultados de Enfermagem

The venous ulcer is an epidemiological problem of high prevalence, causing disability and dependence. Assess the tissue impairment level of patients with venous lesions, within a nursing referential, is relevant for the implementation of a directed assistance to specific clientele. Thus, this work aims to characterize the health status regarding the integrity the lower limbs skin of patients with venous ulcers, according to the of tissue integrity outcome indicators from the Nursing Outcomes Classification. A cross-sectional study conducted in a university hospital in Natal - Rio Grande do Norte. The sample consisted of 50 participants, selected through consecutive sampling. Data collection occurred through a interview and physical examination form and a operational definitions tool for indicators of the nursing Tissue Integrity outcome directed to patients with venous ulcer, applied from February to June 2012. Data analysis was done by descriptive statistics and nonparametric tests (Spearman, Kruskal-Wallis and Mann-Whitney tests). The project was approved by the Research Ethics Committee with protocol 608/11 and Presentation Certificate to Ethical Consideration No. 0038.0.294.000-11. The results were presented using three scientific articles derivatives of research. It was found that the indicators show moderate impairment, light and not impaired, as the median. The respondents had an average of 59.72 years, 66% female, 50% were retired, 60% with a partner, 44% had arterial hypertension, 26% allergies, 20% diabetes mellitus, 96% were sedentary, 14% drank alcohol and 6% were smokers. There was a statistically significant correlation of low intensity between age and hydration (p=0.032; rs=-0.304) and skin desquamation (p=0.026; rs=-0.316), family income and necrosis (p=0.012; rs=-0.353); Ankle Brachial Index and tissue perfusion (p=0,044; rs=-0,329); Diabetes Mellitus and texture (p=0.015) and tissue perfusion (p=0.026); allergy and texture (p=0.034), physical activity and hydration (p=0.034), smoking and thickness (p=0.018), and alcohol consumption and exudate (p=0.045). We conclude that the patients had light to moderate impairment, indicating a good state of health on the integrity of the skin of the lower limbs, according to the indicators of the outcome of tissue integrity Classification Nursing Outcomes valued in the present study. It is believed that the evaluation of impairment tissue using a self-nursing system and its relation with socioeconomic, clinical and risk factors are unique tools in the care planning and in the wound healing

Heat shock proteins (HSP): dermatological implications and perspectives

In recent years, several studies have demonstrated the protective effect of Heat Shock Proteins (HSP) on different organs and tissues under stressful conditions. However, most research explores the performance of those molecular chaperones during immune responses or pathological conditions like cancer, whereas the number of studies related to the performance of HSPs in the skin during diverse natural or physiopathological conditions is very low. Therefore, the aim of this article was to summarize the main concepts concerning the expression and performance of HSPs, from analysis of current medicine and cosmetics publications, as well as exploring the importance of these proteins in the dermatological area in physiological events such as cutaneous aging, skin cancer and wound healing and to present final considerations related to biotechnology performance in this area.

Nitric oxide release using natural rubber latex as matrix

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)