Desenvolvimento de nanopartículas de quitosana para potencial administração nasal da DISBa-01, uma desintegrina recombinante do veneno da serpente Rhinocerophis alternatus

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

Desenvolvimento e caracterização de sistemas nanoestruturados para potencial administração nasal de zidovudina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sistemas nanoestruturados mucoadesivos para administração nasal de zidovudina

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento de nanopartículas de quitosana para adminstração nasal de zidovudina

Zidovudine (AZT) is the drug most commonly used in AIDS treatment, isolated or in combination with other antiretroviral agents, but it has certain limitations due to its therapeutic dose-dependent haematological toxicity. In addition, it has low oral bioavailability, since it undergoes pre-systemic metabolism. The nasal route has been used as an alternative route for drug administration, because it can promote its direct absorption to blood circulation, avoiding hepatic metabolism. However, this route presents as a factor limiting the mucociliary clearance mechanisms that remove quickly the formulation of the nasal cavity. To prolong the residence time of formulations, in this direction, has been proposed the development of mucoadhesive systems. Among the various existing systems, the use of chitosan (QS), as mucoadhesive polymer, has been widely exploited in the preparation of nanoparticles (NPs). The objective of this study was to develop and characterize QS’s NPs for intranasal administration of AZT. For both NPs have been developed by ionic crosslinking of QS with sodium tripolyphosphate (TPP). These NPs were characterized by studies of particle size distribution, zeta potential, morphology, mucoadhesion tests, assessing the ability of encapsulation of the drug and permeation profile of AZT. The evaluation of AZT in the NPs was determined by UV-Vis spectroscopy. Mucoadhesion measures were made using a texture analyzer, using a mucin disk and porcine mucous membrane , and permeation assay were conducted using porcine nasal mucous membrane adapted to the Franz cell. These results suggest that the systems in hand have great potential for nasal AZT administration

Caracterização de sistemas mucoadesivos para potencial administração de zidovudina

A zidovudina (AZT) é um antirretroviral que apresenta baixa biodisponibilidade devido seu intenso metabolismo pré2sistêmico. A via nasal tem sido estudada como alternativa para evitar este efeito, mas possui limitações, como os mecanismos de depuração mucociliar, que podem ser minimizadas através do desenvolvimento de sistemas de liberação mucoadesivos. O presente estudo tem por objetivo caracterizar sistemas tensoativos visando o desenvolvimento de uma formulação mucoadesiva para potencial administração nasal de AZT. Para isso, foi utilizada uma microemulsão (ME) composta por álcool cetílico etoxilado 20 OE e propoxilado 5 OP (PRO), ácido oleico (AO) e água. Foi testada a incorporação de polímeros mucoadesivos – policarbofil (PF), carbopol 971 (C971), 974 (C974) e quitosana (QS) na ME. Os sistemas foram caracterizados por microscopia de luz polarizada (MLP), quantificação do AZT, reologia de fluxo e oscilatória, análise do perfil de textura (TPA) e obtenção da força de mucoadesão. Os resultados mostraram que foi possível incorporar 0,1 % (p/v) dos polímeros e os sistemas incorporaram mais AZT do que a solução aquosa. Os sistemas apresentam fluxo newtoniano. Quando misturados ao muco artificial (MA), os sistemas tiveram G’ aumentado e houve mudança da ME para fase hexagonal. No teste TPA, a dureza da ME contendo PF foi a maior. Pode2se concluir que é possível obter uma formulação precursora de matriz com características de textura e reologia favoráveis à aplicação nasal. O sistema foi capaz de incorporar o AZT e apresentou grande potencial mucoadesivo. Esta estratégia se mostra promissora na melhora da terapia... (Resumo completo, clicar acesso eletrônico abaixo)

Pituitary Macroadenoma Presenting As A Nasal Tumor: Case Report.

Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass. The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases. Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present.

Facial Changes After Early Treatment Of Unilateral Coronal Synostosis Question The Necessity Of Primary Nasal Osteotomy.

The premature fusion of unilateral coronal suture can cause a significant asymmetry of the craniofacial skeleton, with an oblique deviation of the cranial base that negatively impacts soft tissue facial symmetry. The purpose of this study was to assess facial symmetry obtained in patients with unilateral coronal synostosis (UCS) surgically treated by 2 different techniques. We hypothesized that nasal deviation should not be addressed in a primary surgical correction of UCS. Consecutive UCS patients were enrolled in a prospective study and randomly divided into 2 groups. In group 1, the patients underwent total frontal reconstruction and transferring of onlay bone grafts to the recessive superior orbital rim (n = 7), and in group 2, the patients underwent total frontal reconstruction and unilateral fronto-orbital advancement (n = 5). Computerized photogrammetric analysis measured vertical and horizontal axis of the nose and the orbital globe in the preoperative and postoperative periods. Intragroup and intergroup comparisons were performed. Intragroup preoperative and postoperative comparisons showed a significant (all P < 0.05) reduction of the nasal axis and the orbital-globe axis in the postoperative period in the 2 groups. Intergroup comparisons showed no significant difference (all P > 0.05). Facial symmetry was achieved in the patients with UCS who underwent surgery regardless of surgical approach evaluated here. Our data showed a significant improvement in nasal and orbital-globe deviation, leading us to question the necessity of primary nasal correction in these patients.

Nasal Potential Difference In Cystic Fibrosis Considering Severe Cftr Mutations.

The gold standard for diagnosing cystic fibrosis (CF) is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD) test. CFTR gene sequencing can identify CFTR mutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-III CFTR mutations (10 patients) (G1), CF patients with classes IV-VI CFTR mutations (five patients) (G2), and 21 healthy subjects (G3). The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis, χ(2), and Fisher's exact tests, α = 0.05. No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-III CFTR mutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects.

Administração limpa e enxuta em sistemas hidráulicos de colhedoras de cana-de-açúcar

Among the important changes in the production processes, it is necessary to guarantee the sustainability of the human enterprises, what makes us to foresee changes in the managerial administration to adapt to a new model, with the insert of the concepts of Clean Production, Cleaner, Lean and Total Productive Maintenance (TPM). The main focus of this work was to elaborate a methodology that made it possible to guarantee the reliability in the waterworks of the sugarcane harvester, identifying and analyzing the manners of flaws, in order to result in the improvement of the environmental and socioeconomic quality in the atmosphere of an industry of sugarcane through the significant decrease of hydraulic oil spill. Through the existent report in ERP (Enterprise Resource Planning), used in a Sugarcane Industry Plant, it was possible to accompany of the operational acting of the sugarcane harvester used during 03 crops, regarding the manners of flaws in the waterworks of the same ones, and, in one of the crops it was elaborated the total control of the waterworks of 5 harvesters. Based on the obtained data and the developed methodology it was possible to develop a software that specifies the electric outlet of decisions.

Ocular masquerade syndrome associated with extranodal nasal natural killer/T-cell lymphoma: case report

A 33-year-old woman complained of unilateral eyelid edema and blurred vision. Initial ophthalmic examination disclosed anterior chamber reaction with keratic precipitates on the cornea, without posterior abnormalities. Anterior uveitis was treated. Despite that, patient showed rapidly progressive unilateral vision loss with optic nerve swelling. Systemic workup was inconclusive, as well as cranial magnetic resonance imaging and cerebrospinal fluid examination. Based on the hypothesis of optic neuritis, intravenous methylprednisolone pulse was performed with no success. During the following days, the patient presented pericardial effusion and cardiac tamponade, progressing to death. Necropsy was performed and diagnosis of extranodal natural killers/T-cell lymphoma, nasal type with ocular involvement was confirmed by immunohistochemistry.

Angioleiomioma de cavidade nasal: relato de um caso e revisão de literatura

Leiomioma de cavidade nasal e seios paranasais é raro. Ele constitui menos de 1% de todos os leiomiomas do corpo humano. Isto se deve à escassez de células musculares no nariz. Estas neoplasias podem ser classificadas em três grupos: leiomioma, angiomioma e leiomioma epitelióide. Somente 15 casos de angiomioma foram encontrados na literatura. O tratamento de escolha é a excisão cirúrgica. Um novo caso e a revisão da literatura são apresentados.

Rhinometric evaluation of nasal cavity geometry and its relation to the upper arch transverse distance

The objective of this study was to evaluate children's respiratory patterns in the mixed dentition, by means of acoustic rhinometry, and its relation to the upper arch width development. Fifty patients were examined, 25 females and 25 males with mean age of eight years and seven months. All of them were submitted to acoustic rhinometry and upper and lower arch impressions to obtain plaster models. The upper arch analysis was accomplished by measuring the interdental transverse distance of the upper teeth, deciduous canines (measurement 1), deciduous first molars (measurement 2), deciduous second molars (measurement 3) and the first molars (measurement 4). The results showed that an increased left nasal cavity area in females means an increased interdental distance of the deciduous first molars and deciduous second molars and an increased interdental distance of the deciduous canines, deciduous first and second molars in males. It was concluded that there is a correlation between the nasal cavity area and the upper arch transverse distance in the anterior and mid maxillary regions for both genders.

Efeitos da administração de monensina por meio de cápsulas de liberação controlada no desempenho de vacas Holandesas no início da lactação

Com o objetivo de estudar o efeito da monensina sobre a produção e composição de leite, a contagem de células somáticas, a condição corporal e os parâmetros sangüíneos e reprodutivos de vacas da raça Holandesa de alta produção no início de lactação, foram utilizadas 44 vacas com produção diária de 33,44 ± 4,93 litros de leite, em delineamento inteiramente casualizado, com dois tratamentos: um controle (C) e outro com cápsulas de liberação controlada de monensina com eficácia de 100 dias (300 mg/vaca/dia). A administração individual de monensina foi realizada 30 dias antes da data provável do parto. A monensina não alterou a produção, a composição do leite e a contagem de células somáticas do leite nem a condição corporal e a concentração de glicose e BHBA (beta-hidroxibutirato) no soro das vacas, no entanto, diminuiu a concentração de AGNE (ácidos graxos não-esterificados) no soro das vacas com 60 dias de lactação. O período de serviço e o número de serviços por concepção não diferiram entre os tratamentos, porém, a administração de monensina diminuiu o número de animais que apresentaram retenção de placenta e laminite. A administração de monensina para vacas Holandesas de alta produção no início de lactação não modifica a produção e a composição do leite, contudo, diminui a concentração de AGNE 60 dias após o parto e a incidência de laminite e retenção de placenta nas vacas no pós-parto.

Photographic assessment of nasal morphology following rapid maxillary expansion in children

OBJECTIVE: The aim of the present study was to use facial analysis to determine the effects of rapid maxillary expansion (RME) on nasal morphology in children in the stages of primary and mixed dentition, with posterior cross-bite. MATERIAL AND METHODS: Facial photographs (front view and profile) of 60 patients in the pre-expansion period, immediate post-expansion period and one year following rapid maxillary expansion with a Haas appliance were evaluated on 2 occasions by 3 experienced orthodontists independently, with a 2-week interval between evaluations. The examiners were instructed to assess nasal morphology and had no knowledge regarding the content of the study. Intraexaminer and interexaminer agreement (assessed using the Kappa statistic) was acceptable. RESULTS: From the analysis of the mode of the examiners' findings, no alterations in nasal morphology occurred regarding the following aspects: dorsum of nose, alar base, nasal width of middle third and nasal base. Alterations were only detected in the nasolabial angle in 1.64% of the patients between the pre-expansion and immediate post-expansion photographs. In 4.92% of the patients between the immediate post-expansion period and 1 year following expansion; and in 6.56% of the patients between the pre-expansion period and one year following expansion. CONCLUSIONS: RME performed on children in stages of primary and mixed dentition did not have any impact on nasal morphology, as assessed using facial analysis.

Efeitos da administração diária da associação estavudina/nelfinavir sobre os fetos e placentas da rata albina

OBJETIVO: avaliar o efeito da administração da associação estavudina/nelfinavir durante toda a prenhez da rata, avaliando seu peso e dos conceptos, bem como o número de implantações, fetos, placentas, reabsorções e mortalidades materna e fetal. MÉTODOS: quarenta ratas albinas EPM-1 Wistar, prenhes, foram aleatoriamente divididas em quatro grupos: GCtrl (controle do veículo) e três experimentais, ExpI, ExpII e ExpIII, que receberam, respectivamente, 1/40, 3/120 e 9/360 mg/kg por dia de estavudina/nelfinavir por via oral. As drogas e o veículo (água destilada) foram administrados por gavagem em duas tomadas diárias (12/12 horas), desde o dia 0 até o 20º dia da prenhez. No último dia do experimento, todos os animais foram anestesiados e eutanasiados. Foram avaliados a evolução do peso materno no 7º, 14º e 20º dias, número de fetos, placentas, implantações, reabsorções, óbitos intrauterinos, malformações maiores e o peso dos fetos e das placentas. A análise estatística foi realizada por análise de variância (ANOVA), complementada pelo teste de Kruskal-Wallis (p<0,05). RESULTADOS: em relação ao peso corporal das ratas, houve ganho gradual e progressivo durante o decorrer da prenhez em todos os grupos, sendo este ganho mais evidente no período final; porém não foram constatadas diferenças estatisticamente significantes entre eles. O número de fetos, placentas, implantações, assim como os pesos fetais e placentários também não mostraram diferenças estatisticamente significantes entre os grupos analisados. Não foram observadas, também nos grupos experimentais, reabsorções e malformações fetais maiores externas, no entanto, observamos entre o 8º e o 14º dias de gestação um caso de morte materna em cada grupo experimental. CONCLUSÕES: a administração da associação estavudina/nelfinavir não mostrou efeitos deletérios sobre os conceptos.