Spray-dried raloxifene submicron particles for pulmonary delivery: Development and in vivo pharmacokinetic evaluation in rats.

Raloxifene hydrochloride (RH) is a selective oestrogen receptor modulator used for the treatment of osteoporosis. Even though 60% of an oral dose is quickly absorbed via the gastrointestinal tract, the absolute bioavailability of RH is only 2-3% in humans due to extensive first-pass metabolism. Various approaches to improve RH bioavailability have been reported over the past few years; however, none have focused on the development of products for pulmonary administration. Therefore, in this study, submicron particles containing RH were produced for pulmonary administration with the aim to limit first-pass metabolism. Powders were produced by vibrational atomisation spray drying with a high process yield (>80%). The drug content was between 440 and 890 mg·g-1, and powders had a high encapsulation efficiency (>95%), mean particle size of 400-700 nm, low residual moisture (<2%) and spherical shape. These powders showed an improved drug dissolution rate compared to the raw RH material. Moreover, they presented high dose uniformity (95-100%), a high in vitro respirable fraction (>55%) and adequate mass median aerodynamic diameter for pulmonary delivery (<5 µm). The pharmacokinetic study in male Wistar rats demonstrated an absolute bioavailability of 47.20% after pulmonary administration of the particles. Therefore, these submicron-sized powders are promising for pulmonary RH delivery as a dry powder medicine.

LC-UV method to assay raloxifene hydrochloride in rat plasma and its application to a pharmacokinetic study

A specific, precise, and accurate LC-UV method was developed and validated to assay raloxifene hydrochloride in rat plasma. Raloxifene was analyzed after liquid-liquid extraction and quantified by reversed phase liquid chromatography (C18 column) using acetonitrile and ammonium acetate buffer 0.05 M (pH 4.0) as mobile phase at a flow rate of 1 mL.min-1 and UV detection at 287 nm. Retention times of raloxifene and internal standard (dexamethasone) were approximately 11 min and 14 min, respectively. Linearity was checked for a concentration range between 25 ng.mL-1 and 1000 ng.mL-1. Intra- and inter-day precision had relative standard deviation lower than 10% and 15%, respectively. Recovery from plasma was higher than 90%. Accuracy values were 98.21%, 99.70%, and 102.70% for lower, medium, and upper limits of quantification, respectively. Limit of quantification was 25 ng.mL-1. Drug stability was analyzed at room temperature using plasma kept in a freezer at -80 °C for 45 days after processing for 6 h and three freeze-thaw cycles. The advantages of the method developed include stability under different conditions and low limit of quantification. Its applicability was confirmed by the analysis of raloxifene levels in plasma samples in a designed pharmacokinetic study in rats after intravenous administration (5 mg.kg-1).

Nanoencapsulation of Clobetasol Propionate Decreases Its Penetration to Skin Layers Without Changing Its Relative Skin Distribution.

An immunosuppressive effect with drug release control and higher NTPDase activity in the treatment of contact dermatitis was previously reported for a hydrogel containing 0.05% clobetasol propionate-loaded lipid-core nanocapsules (HG-LNC-CP) compared to a hydrogel containing the non-encapsulated drug (HG-CP). In order to investigate the factors underlying this different performance, we evaluated the in vitro skin permeation/penetration of CP from both formulations (HG-LNC-CP and HG-CP). CP did not permeate to the receptor medium during the experiment (24 h), but penetrated into the stratum corneum and viable skin (epidermis and dermis) in significant amounts after 24 h, regardless the type of the formulation. Comparing both formulations, although the relative amount of CP in each skin layer was not affected by the nanoencapsulation, HG-LNC-CP was able to reduce in 5.8, 6.9 and 3.7 times the amount of CP released into the stratum corneum, epidermis and dermis respectively. In this way, the higher effect of HG-LNC-CP previously observed could be due to the controlled drug penetration rate into the skin layers. Moreover, HG-LNC-CP reduces the chances of the corticosteroid to be absorbed systemically as the amount of CP reaching the dermis was reduced. The study reinforces the HG-LNC-CP as a promising dermatological nanomedicine for the treatment of skin disorders.

Controlled release of raloxifene by nanoencapsulation: effect on in vitro antiproliferative activity of human breast cancer cells.

Raloxifene hydrochloride (RH) is considered to be an antiproliferative agent of mammary tissue. The aim of this study was to investigate the effect of the encapsulation of RH in polymeric nanocapsules with anionic or cationic surface on its release profile and antiproliferative activity. They were prepared by interfacial deposition of preformed polymer, followed by wide physicochemical characterization. The in vitro RH release was assessed by the dialysis membrane method and the data analyzed by mathematical modeling. The antiproliferative effect on MCF-7 cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as well as by counting viable cells. They had high encapsulation efficiency, low polydispersity, and nanometric mean size. Nanocapsules prepared with Eudragit(®) RS100 and Eudragit(®) S100 presented positive and negative zeta potentials, respectively. Drug release studies demonstrated controlled release of RH from anionic nanocapsules, which could be explained due to a stronger interaction of the drug to these nanocapsules and the larger amount of entrapped drug. On the other hand, this control was not observed from cationic nanocapsules due to the larger amount of drug adsorbed onto their surface. MCF-7 cell viability studies and cell counting showed that RH-loaded Eudragit(®) RS100 nanocapsules promote the best antiproliferative activity after 24 hours of treatment, whereas the best activity was observed for RH-loaded Eudragit(®) S100 nanocapsules after 72 hours. Furthermore, the combined treatment of these formulations improved the antiproliferative effect during the entire treatment.

An experimental model of contact dermatitis: evaluation of the oxidative profile of Wistar rats treated with free and nanoencapsulated clobetasol.

OBJECTIVE: An experimental animal model of contact dermatitis (CD) was used to investigate the effects of free and nanoencapsulated clobetasol propionate on the skin and on the oxidative profile of liver tissue. METHODS: Female Wistar rats were divided into six groups, each containing eight rats. The first group, control (C), was sensitized with solid vaseline. Group 2, (CD), was sensitized with 5% NiSO(4). Groups 3 and 4 were sensitized with 5% NiSO(4) and treated with free (FC) and nanoencapsulated (NC) clobetasol (0.42 mg/g), respectively, daily for 5 days. Group 5 was treated with nanoencapsulated clobetasol (0.42 mg/g) on days 1, 3, and 5 (C135) and group 6 received a hydrogel containing empty nanoparticles (NP) daily for 5 days. Thiobarbituric acid reactive substances (TBARS), carbonyl levels, non-protein sulfhydryl groups (NPSH) and catalase activity were measured in liver homogenates. RESULTS: A significant increase was observed in the levels of TBARS, NPSH, and catalase activity for the groups CD and NP. DISCUSSION: Our results suggest that both NiSO(4) sensitization and NP administration induced oxidation of cellular lipids and activated the antioxidant enzyme catalase to protect from this damage. These results also indicated that daily treatment with the free and nanoencapsulated clobetasol, as well as treatment with the nanoencapsulated clobetasol every other day, were able to prevent these redox alterations and protect against histological damage.

Doença de von Recklinghausen / Von Recklinghausen

Descreve-se um caso de NFI que se apresentou com quadro clínico típico e exuberante. Acredita-se que a riqueza dos achados clínicos deste paciente poderá ajudar no reconhecimento desta patologia e de suas complicações. Apresenta-se, ain- da, uma breve revisão da literatura e su gestões para diagnóstico e acompanha- mento dos Dacientes.

Acidentes biológicos em Hospital Universitário / Biological accidents in a School Hospital

Os profissionais da saúde estão frequentemente expostos a acidentes com material biológico e, dentre as doenças de possível contaminação, as hepatites e a AIDS são as que mais preocupam essa categoria. Foi realizada análise retrospectiva de todas as notificações referentes a esses acidentes arquivados junto ao SESMT durante o período de 1 ano, com o objetivo de quantificar o número de acidentes biológicos, avaliar qual a equipe profissional mais sujeita a esses acidentes e identificar os motivos e locais mais prevalentes de sua ocorrência.Uma vez observado que a maior foi o descaso em seguir as normas recomendadas, os autores apontam a necessidade de um treinamento continuado dos profissionais da área para a redução de riscos ocupacionais

Patologias benignas da mama / Benign breast diseases

As duas lesões benignas predominantes na literatura são os fibroadenomas e as alterações fibrocísticas. O objetivo deste estudo foi estimar a prevalência destes tumores na área de abrangência do Intituto de Patologia, em Passo Fundo e regiões vizinhas, considerando localização, idade e frequência em uma análise dos últimos 10 anos. Os autores concluem que as doenças benignas da mama merecem atenção especial por sua alta prevallência, seu impacto na qualidade de vida do paciente e, para alguns tipos histológicos, seu potencial de malignização. Além disso, o diagnóstico clínico, radiológico e ecográfico desses tumores pode simular uma neoplasia maligna de mama

Utilizaçäo de Ceftriaxona no Hospital Universitário de Passo Fundo / Ceftriaxone in the School Hospital of the University of Passo Fundo Medical School, Passo Fundo/RS, Brazil

Os antimicrobianos são os fármacos de uso mais prevalente em hospitais, acarretando significativos gastos hospitalares. Tal uso deve ser judicioso e restrito em algumas circunstâncias, pois o mau emprego pode trazer, como consequência, desnecessário dispêndio e resistência microbiana. O presente trabalho avalia as condições locais de emprego de Ceftriaxona, que apresenta prescrição predominante em Hospital Universitário, comparando-as com critérios definidos como corretos. Uma vez que o uso justificado, conforme critérios pré-determinados, ocorreu somente em 16 casos dos 100 formulários e prontuários analisados e que em 42 pacientes houve erro relacionado à duração do tratamento, os autores concluem que os prescritores devam ser conscientizados para o uso racional deste fármaco

Errata de: Linfoma cutâneo de células T: Relato de caso / Erratum to: Cutaneous T-cell lymphoma: Case Repor

A micose fungóide é uma entidade clínica do linfoma cutâneo de células T (LCCT), desordem maligna, caracterizada pela ocorrência de uma população monoclonal de linfóticos T. Os autores apresentam um caso dessa forma clínica com o objetivo de discutir, principalmente, aspectos relacionados ao quadro clínico, dando ênfase para o diagnóstico precoce das lesões iniciais dessa patologia, pela sua similaridade a outras dermatoses benignas

Tratamento das neoplasias malignas de cólon e reto / Treatment of malignant neoplasms of the colon and rectum

O presente trabalho objetiva avaliar o tratamento cirúrgico do carcinoma coloretal, considerando localização, tipo histológico, estadiamento, diferenciação, tempo de internação hospitalar e morbi-mortalidade. Trata-se de um estudo transversal prospectivo referente a 63 pacientes com câncer colo-retal, atendidos no HSVP, no período de 1993 a 1999. A região mais afetada foi o cólon e o tipo histológico predominante foi o adenocarcinoma, com 70,5 por cento das lesões estágio II e III, incidindo tumores bem e moderadamente diferenciados. Dentre os 63 pacientes atendidos, em 92 por cento foi realizada ressecção cirúrgica da lesão primária. Cinco (8 por cento) foram submetidos a ostomias com intenção paliativa. Ocorreram complicações pós-operatórias em 17 por cento dos casos, sendo retenção urinária a mais frequente. O tempo médio de internação hospitalar foi de 15 dias e ocorreram 5 óbitos pós-operatórios. Os autores concluem que a baixa mortalidade e as complicações pós-operatórias, a despeito dos extensos procedimentos cirúrgicos realizados, foram comparáveis às descritas na literatura

Linfoma cutâneo de células T / Cutaneous T -Cell lymphoma

A micose fungóide é uma entidade clínica do linfoma cutâneo de células T (LCCT), desordem maligna, caracterizada pela ocorrência de uma população monoclonal de linfócitos T. Os autores apresentam um caso dessa forma clínica com o objetivo de discutir, principalmente, aspectos relacionados ao quadro clínico, dando ênfase para o diagnóstico precoce das lesões iniciais dessa patologia, pela sua similaridade a outras dermatoses benignas

Tuberculose pulmonar no paciente HIV positivo / Pulmonary tuberculosis in HIV positive patients

Os autores apresentam a análise retrospectiva de doze pacientes HIV positivos com diagnóstico de tuberculo pulmonar internados no HUSVP de Passo Fundo, RS, durante o ano de 1997. Foram observados o perfil dos pacientes, sinais clínico-radiológicos e laboratoriais, métodos diagnósticos e o tratamento utilizado

Involução de litíase renal com citrato de potássio e hidroclorotiazida / Clinical treatment of renal lithiasis with potassium citrate and hidroclorotiazide: a case report

Recentemente tem surgido estudos buscando comprovar os efeitos benéficos da terapêutica com citrato de potássio para prevenção e tratamento da litíase renal. Os autores relatam um caso de involução de cálculo renal e revisam a literatura atual sobre a patogenia dos cálculos, tratamentos disponíveis e prevenção de recidivas

Síndrome de Guillain-Barré na infância / Guillain-Barre syndrome in childhood

A ocorrência de desmielinização aguda do sistema nervoso periférico de gravidade variável, após doenças infecciosas é reconhecida há longo tempo. Relata-se caso de Síndrome de Guillain-Barré em criança, ocorrida após infecção respiratória...

Infarto agudo do miocárdio e Síndrome da Imunodeficiência Adquirida / Acute myocardial infarction in patient with AIDS

Os autores relatam o caso de um paciente com AIDS que apresentou infarto agudo do miocárdio durante internaçäo hospitalar. Além disso, säo feitas consideraçöes sobre a possibilidade do HIV estar relacionado, como fator predisponente, no desenvolvimento de infarto agudo do miocárdio