Solid Lipid Nanoparticles As Nucleic Acid Delivery System: Properties And Molecular Mechanisms.

Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate drug delivery systems, and ever since they have been applied in a wide variety of cosmetic and pharmaceutical applications. In addition, SLNs are considered suitable alternatives as carriers in gene delivery. Although important advances have been made in this particular field, fundamental knowledge of the underlying mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative requirement in efforts aimed at further improving their efficiency. Here, we address recent advances in the use of SLNs as platform for delivery of nucleic acids as therapeutic agents. In addition, we will discuss available technology for conveniently producing SLNs. In particular, we will focus on underlying molecular mechanisms by which SLNs and nucleic acids assemble into complexes and how the nucleic acid cargo may be released intracellularly. In discussing underlying mechanisms, we will, when appropriate, refer to analogous studies carried out with systems based on cationic lipids and polymers, that have proven useful in the assessment of structure-function relationships. Finally, we will give suggestions for improving SLN-based gene delivery systems, by pointing to alternative methods for SLNplex assembly, focusing on the realization of a sustained nucleic acid release.

Effect Of Pain Chronification And Chronic Pain On An Endogenous Pain Modulation Circuit In Rats.

We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain.

Aplicação do escore MELD em pacientes submetidos a transplante de fígado: análise retrospectiva da sobrevida e dos fatores preditivos a curto e longo prazo

BACKGROUND: The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. There are few reports studying the correlation between MELD and long-term posttransplantation survival. AIM: To assess the value of pretransplant MELD in the prediction of posttransplant survival. METHODS: The adult patients (age >18 years) who underwent liver transplantation were examined in a retrospective longitudinal cohort of patients, through the prospective data base. We excluded acute liver failure, retransplantation and reduced or split-livers. The liver donors were evaluated according to: age, sex, weight, creatinine, bilirubin, sodium, aspartate aminotransferase, personal antecedents, brain death cause, steatosis, expanded criteria donor number and index donor risk. The recipients' data were: sex, age, weight, chronic hepatic disease, Child-Turcotte-Pugh points, pretransplant and initial MELD score, pretransplant creatinine clearance, sodium, cold and warm ischemia times, hospital length of stay, blood requirements, and alanine aminotransferase (ALT >1,000 UI/L = liver dysfunction). The Kaplan-Meier method with the log-rank test was used for the univariable analyses of posttransplant patient survival. For the multivariable analyses the Cox proportional hazard regression method with the stepwise procedure was used with stratifying sodium and MELD as variables. ROC curve was used to define area under the curve for MELD and Child-Turcotte-Pugh. RESULTS: A total of 232 patients with 10 years follow up were available. The MELD cutoff was 20 and Child-Turcotte-Pugh cutoff was 11.5. For MELD score > 20, the risk factors for death were: red cell requirements, liver dysfunction and donor's sodium. For the patients with hyponatremia the risk factors were: negative delta-MELD score, red cell requirements, liver dysfunction and donor's sodium. The regression univariated analyses came up with the following risk factors for death: score MELD > 25, blood requirements, recipient creatinine clearance pretransplant and age donor >50. After stepwise analyses, only red cell requirement was predictive. Patients with MELD score < 25 had a 68.86%, 50,44% and 41,50% chance for 1, 5 and 10-year survival and > 25 were 39.13%, 29.81% and 22.36% respectively. Patients without hyponatremia were 65.16%, 50.28% and 41,98% and with hyponatremia 44.44%, 34.28% and 28.57% respectively. Patients with IDR > 1.7 showed 53.7%, 27.71% and 13.85% and index donor risk <1.7 was 63.62%, 51.4% and 44.08%, respectively. Age donor > 50 years showed 38.4%, 26.21% and 13.1% and age donor <50 years showed 65.58%, 26.21% and 13.1%. Association with delta-MELD score did not show any significant difference. Expanded criteria donors were associated with primary non-function and severe liver dysfunction. Predictive factors for death were blood requirements, hyponatremia, liver dysfunction and donor's sodium. CONCLUSION: In conclusion MELD over 25, recipient's hyponatremia, blood requirements, donor's sodium were associated with poor survival.

Adequação de engates rápidos de aspersores como conectores de mangueira para distribuição de água em sulcos de irrigação

As a way to reduce water losses in furrow irrigation systems, used in fresh market tomato production, farmers are improperly distributing water into the field using plastic hose. The objective of this work was to study the suitability of using quick coupler sprinkler as hose connectors for water distribution in tomato plantation. The first step of the study was to assess the current hose field operation for tomato growers. Subsequently, four models of quick couplers sprinklers available in the market were tested in laboratory to determine the coefficient of resistance, the equivalent tube length, the head loss curve and the linking efficiency. As result, a structural design for hose connectors was presented using the model of coupling with the best hydraulic performance. Additionally, some technical recommendations on its use in irrigation water distribution are highlighted. Despite the requirement for additional field trials, the proposed system has potential to optimize the water use efficiency, to improve workers ergonomic conditions, and ensure good profitability to the producer.

Estruturas factivas e padrões de extração

This paper investigates the relationship between structural and semantic properties of factive sentences and the pattern of extraction exhibited. It is argued that a classification as weak or strong island is unfeasible for what has been termed Factive Island. The kinds of structures allowed as factive complements are analyzed as well as their corresponding behavior concerning extraction. The common feature these structures show is their presuppositional character, which is derived from a selection requirement. I assume that factive predicates select a [+ specific] complement. The differences showed concerning extraction constitute a spontaneous effect from the structural way each construction may satisfy this requirement.

Estudo inicial da degradação in vivo de poli(L-co-D,L ácido lático), sintetizado em laboratório, aplicado como prótese tibial em coelhos

The copolymer poly (L-co-D,L lactic acid), PLDLA, has gained prominence in the field of temporary prostheses due to the fact that their time of degradation is quite compatible with the requirement in the case of osseous fracture. In this work the in vivo degradation of devices from copolymer, as a system of plates and screws, used in fixation of the tibia of rabbits was studied. The devices were implanted in 15 adult rabbits, albinos, New Zealand race, and they were used as control devices of alloys of titanium (Ti-6Al-4V/ V grade). The use of copolymers, synthesized in the laboratory, was tested in the repair of fracture in rabbits'tibias, being assessed in the following times: 2 weeks, 2 months and 3 months. Morphological analysis of tissue surrounding the plate and screw system, for 2 weeks of implantation, showed the presence of osteoblasts, indicating a pre bone formation. After 2 months there was new bone formation in the region in contact with the polymer. This bone growth occurred simultaneously with the process of PLDLA degradation, invading the region where there was polymer and after 3 months there was an intense degradation of the copolymer and hence greater tissue invasion compared to 2 months which characterized bone formation in a region where the polymer degraded. The in vivo degradation study of the devices for PLDLA by means of histological evaluations during the period of consolidation of the fracture showed the efficiency of plate and screw system, and it was possible to check formation of bone tissue at the implantation site, without the presence of inflammatory reaction

Nossa notação m' na prova de Rorschach: ampliação e restrição do fator m de Klopfer

Klopfer's differentiation of movement scores, among which inanimate movement integrating the minor movements group, was no doubt opportune and needed. Their peculiar meaning has been clearly stressed and enriched by Piotrowski in his reformulation of Rorschach variables. It is our belief that Rorschach himself would take such step. Our criteria for scoring this determinant are somewhat different of both Klopfer's and Piotrowski's. On the one hand, masks, facial traits, emotional expressions, body parts in motion are not entered there. On the other, we score as such human or animal movement, provided this does not originate in the blot shape directly, but in the subjective reaction against the sensed muscular tension. Basic requirement for this scoring is the kinesthetic component, as for Mever since Rorschach's elaboration; and common trait distinctive for any response to be so scored ? be it an abstraction, an inanimate object, an animal or human being ? must be the subjective way of feeling the movement: (a) intention, blocking, struggle for achieving, for instance, or (b) activity of nature elements. Due to this subjective meaning we use the symbol m'intead of mfor this category. We already find these two kinds (a) and (b) of movement responses in Rorschach's text, respectively in the Examplesand in his posthumous Contribution.Either may point to a flight from emotional stress or to outstanding mental ability.

Proposta de avaliação motora para portadores de deficiencia visual em coordenação, equilibrio e orientação espacial

Universidade Estadual de Campinas . Faculdade de Educação Física

A recreação/lazer e a educação fisica : a manobra da autenticidade do jogo

Universidade Estadual de Campinas. Faculdade de Educação Física

A inteligencia corporal : cinestesica como manifestação da inteligencia humana no comportamento de crianças

Universidade Estadual de Campinas . Faculdade de Educação Física

Desenvolvimento de uma metodologia para reconstrução da superficie do pe humano por videogrametria

Universidade Estadual de Campinas . Faculdade de Educação Física