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‣ Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting

Serralheiro, Ana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Português
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The currently available antiepileptic drugs are typically administered via oral or intravenous (IV) routes which commonly exhibit high systemic distribution into non-targeted tissues, leading to peripheral adverse effects and limited brain uptake. In order to improve the efficacy and tolerability of the antiepileptic drug therapy, alternative administration strategies have been investigated. The purpose of the present study was to assess the pharmacokinetics of carbamazepine administered via intranasal (IN) and IV routes to mice, and to investigate whether a direct transport of the drug from nose to brain could be involved. The similar pharmacokinetic profiles obtained in all matrices following both administration routes indicate that, after IN delivery, carbamazepine reaches quickly and extensively the bloodstream, achieving the brain predominantly via systemic circulation. However, the uneven biodistribution of carbamazepine through the brain regions with higher concentrations in the olfactory bulb and frontal cortex following IN instillation, in comparison with the homogenous brain distribution pattern after IV injection, strongly suggests the involvement of a direct transport of carbamazepine from nose to brain. Therefore, it seems that IN delivery represents a suitable and promising alternative route to administer carbamazepine not only for the chronically use of the drug but also in emergency conditions.

‣ Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson`s Disease

PREDIGER, Rui D. S.; AGUIAR JR., Aderbal S.; ROJAS-MAYORQUIN, Argelia Esperanza; FIGUEIREDO, Claudia P.; MATHEUS, Filipe C.; GINESTET, Laure; CHEVARIN, Caroline; BEL, Elaine Del; MONGEAU, Raymond; HAMON, Michel; LANFUMEY, Laurence; RAISMAN-VOZARI, Rita
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
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Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson`s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD...

‣ Potencial de abuso do midazolam intranasal em usuários de cocaína aspirada e voluntários normais; Abuse liability of intranasal midazolam in intranasal cocaine users and healthy volunteers

Braun, Ivan Mario
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 25/10/2012 Português
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INTRODUÇÃO: O midazolam é uma imidazobenzodiazepina usada para induzir o sono, produzir sedação antes de procedimentos dolorosos e no tratamento do estado de mal epiléptico. Seu uso pela via intranasal proporciona um rápido início de ação e esta via, em muitos casos, pode substituir as vias endovenosa e intramuscular, mais invasivas. Assim, o midazolam intranasal tem sido sugerido no tratamento extra-hospitalar de crises epilépticas e ataques de pânico. Por outro lado, os benzodiazepínicos possuem um potencial para serem abusados, principalmente em usuários de outras drogas. OBJETIVO: o presente estudo objetivou verificar o potencial de abuso do midazolam intranasal numa população experiente no uso intranasal de substâncias - abusadores de cocaína aspirada. MÉTODOS: Foram estudados 31 voluntários abusadores ou dependentes de cocaína e 34 controles saudáveis, subdivididos em quatro grupos: Abusadores de Cocaína (N = 16) e Voluntários Saudáveis (N= 17) que receberam midazolam (0,5 mg de hidrocloreto de midazolam em cada narina), e Abusadores de Cocaína (N = 15) e Voluntários Saudáveis (N = 17) que receberam o mesmo volume de um placebo ativo. As variáveis de resposta foram a Apreciação da Substância (AS) e a Vontade de Repetir o Uso da Substância (VR)...

‣ Utilização do midazolam intranasal como sedativo para tomografia em crianças; Utilization of aerosolized intranasal midazolam as a single sedative for pediatric tomographic studies

Mekitarian Filho, Eduardo
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 11/03/2013 Português
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38.00227%
Objetivos: Avaliar a segurança e a eficácia do midazolam intranasal (MIN) para sedação para tomografia em crianças, bem como a qualidade dos estudos radiológicos obtidos com esta técnica. Material e métodos: Entre dezembro de 2011 e julho de 2012, este estudo prospectivo avaliou o MIN como sedativo para crianças submetidas à tomografia sem acesso venoso. Após aprovação do Comitê de Ética em Pesquisa e consentimento dos responsáveis, 0,4 mg/kg de MIN foi administrado, sendo feita dose adicional de 0,1 mg/kg se o nível de sedação avaliado pela Escala de Sedação de Ramsay não fosse atingida após 15 minutos da primeira dose. Os desfechos relacionados à sedação incluíram tempo para sedação e para atingir os critérios de alta; parâmetros fisiológicos como oximetria de pulso e frequência cardíaca foram registrados a cada cinco minutos até a alta. A qualidade dos exames tomográficos foi avaliada quanto à presença de artefatos de imagem e movimento. Resultados: 60 eventos de sedação foram realizados em 58 pacientes. A idade média foi de 15,5 meses, sendo 90,9% dos exames tomográficos de crânio. O tempo médio para sedação foi de 15,2 minutos (5-40) e o tempo médio para atingir os critérios de alta foi de 74...

‣ Avaliação do perfil farmacocinético da administração intranasal de guanosina e seu potencial neuroprotetor em um modelo de isquemia do córtex parietal cerebral por termocoagulação em ratos

Ramos, Denise Barbosa
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Dissertação Formato: application/pdf
Português
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A isquemia cerebral é uma das principais causas de morte no mundo, sendo decorrente de uma interrupção transitória ou permanente do fluxo sanguíneo, podendo levar à massiva morte neuronal. Um dos eventos neurotóxicos relacionados à isquemia é o aumento excessivo da concentração de glutamato extracelular, o que leva a hiperestimulação do sistema glutamatérgico (excitotoxicidade) podendo assim desencadear uma cascata de eventos intracelulares nos neurônios culminando em sua morte. Nos últimos anos, o nucleosídeo guanosina tem ganhado atenção dos pesquisadores devido ao seu potencial efeito neuroprotetor frente a insultos envolvendo excitotoxicidade. Na maioria dos experimentos in vivo no qual foram observados efeitos neuroprotetores, a guanosina foi administrada sistemicamente, apresentando considerável variabilidade na magnitude de seus efeitos entre os animais. Dado que a guanosina é uma molécula endógena, podendo ser rapidamente metabolizada via sistêmica até alcançar o cérebro, novas vias de administração devem ser exploradas a fim de maximizar seus efeitos neuroprotetores. A administração pela via intranasal tem se mostrado uma excelente alternativa visto que a boa perfusão da mucosa nasal fornece um excelente local para uma rápida absorção de drogas e transporte para o cérebro via líquido cefalorraquidiano (liquor). Neste sentido...

‣ Intranasal delivery of zidovudine by PLA and PLA-PEG blend nanoparticles

Mainardes, Rubiana Mara; Khalil, Najeh Maissar; Daflon Gremiao, Maria Palmira
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 266-271
Português
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 05/50994-6; This study describes the preparation and evaluation of biodegradable poly(L-lactide) (PLA) and poly(L, lactide)-poly(ethylene glycol) (PLA-PEG) blend nanoparticles containing zidovudine as model drug. The prepared nanoparticles were characterized in terms of size, zeta potential, morphology and drug entrapment efficiency. The pharmacokinetics of zidovudine following intranasal administration in mice was assessed. The results showed that although PLA and blend nanoparticles had the same morphology, the particle size and zeta potential were changed by the PEG. The drug entrapment efficiency was increased by PEG presence. The pharmacokinetic study showed that all the nanoparticles were able to sustain zidovudine delivery over time, but greater efficiency was obtained with PLA-PEG blend nanoparticles, whose T(max) was twice that of PLA nanoparticles. The PLA and PLA-PEG nanoparticles formulations increased the zidovudine mean half-life by approximately 5.5 and 7 h, respectively, compared to zidovudine aqueous solution. The relative bioavailability of zidovudine-loaded PLA-PEG blend nanoparticles was 2.7, relative to zidovudine-loaded PLA nanoparticles and 1.3 relative to aqueous solution formulation. Thus...

‣ Reversed phase HPLC determination of zidovudine in rat plasma and its pharmacokinetics after a single intranasal dose administration

Mainardes, Rubiana M.; Gremiao, Maria Palmira D.
Fonte: Soc Biolgia Chile Publicador: Soc Biolgia Chile
Tipo: Conferência ou Objeto de Conferência Formato: 357-364
Português
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 05/50994-6; The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of zidovudine in rat plasma and its application to a pharmacokinetic study following a single intranasal dose zidovudine is described. Zidovudine was extracted from the plasma using, a single-step deproteinization. Chromatographic separation of zidovudine from interfering components wits achieved with a C-18 reverse phase column, a mobile phase Consisting of a mixture of sodium acetate buffer (55 mM) with pH adjusted to 7.0 and acetonitrile (91: 9 v/v) and UV detection set at 265 run. The method was linear from 100 to 10000 ng.mL(-1) (r(2) >= 0.9995), and zidovudine had a mean recovery from plasma of 92.8%. The coefficient of variation of inter-day and intra-day quality control samples was less than 15%. After a single intranasal dose of zidovudine administered to rats, pharmacokinetic parameters (AUC(0-24), C(max), t(max), t(1/2)) were determined. The proposed method was found to be simple, specific. accurate, and precise and could be applied to the quantitative analysis of clinical pharmacokinetic studies of zidovudine in rats.

‣ Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery

Mainardes, Rubiana Mara; Cocenza Urban, Maria Cristina; Cinto, Priscila Oliveira; Chaud, Marco Vinícius; Evangelista, Raul Cesar; Daflon Gremião, Maria Palmira
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Revisão Formato: 275-285
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The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery. © 2006 Bentham Science Publishers Ltd.

‣ Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy

Carvalho, Flávia Chiva; Campos, Michel Leandro; Peccinini, Rosângela Gonçalves; Gremião, Maria Palmira Daflon
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 219-227
Português
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The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT). The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior. Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior. Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1:1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD). Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G′) at nasal temperatures. Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion. Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation. The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms. Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20...

‣ Utilização da provocação nasal com histamina e avaliação rinomanometrica em estudos de bioequivalencia para sprays nasais; Use of histamine nasal challenge and rhinomanometry evaluation in bioequivalence studies for nasal sprays

Natalia Eliza Zanellato Fabbri
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 20/08/2009 Português
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Rinite alérgica é uma doença comum com ampla morbidade, que gera aumento considerável nos custos de tratamento médico, redução da produtividade no trabalho e absenteísmo escolar. A aplicação tópica de corticosteróides intranasal é amplamente reconhecida como primeira linha de tratamento antiinflamatório. Espera-se que a maioria dos sprays nasais prescritos como drogas de ação local, ainda não possuam patente permitindo o aumento de cópias genéricas desses medicamentos, levando a concorrência e redução de preço. Estudos de bioequivalência para sprays nasais estão ainda em discussão. Geralmente, os estudos para essa finalidade usa modelos de intervenção terapêutica a longo prazo, com altos custos para o paciente e longo tempo de duração. O objetivo deste trabalho foi mostrar a aplicabilidade da provocação nasal com histamina e rinomanometria em estudos de bioequivalência para sprays nasais. Trata-se de um estudo aberto, cruzado aleatorizado, utilizando dois períodos e duas seqüências para avaliar a equivalência farmacodinâmica entre duas formulações de sprays de dipropionato de beclometasona de manufaturamento distinto. Após estímulo nasal com histamina (0,5 mg/ml em ambas narinas), 25 voluntários saudáveis foram submetidos a rinomanometria anterior nos tempos 0; 15; 30 e 60 minutos para estabelecimento do fluxo...

‣ Intranasal steroids for acute sinusitis

Zalmanovici Trestioreanu, Anca; Yaphe, John
Fonte: Cochrane Collaboration Publicador: Cochrane Collaboration
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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Acute sinusitis is a common reason for primary care visits. It causes significant symptoms and often results in time off work and school.

‣ Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration

Ducharme, Nicole; Banks, William A.; Morley, John E.; Robinson, Sandra M.; Niehoff, Michael L.; Mattern, Claudia
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Neurosteroids hold great promise for the treatment of diseases of the central nervous system (CNS). We compared the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection. Both neurosteroids appeared in blood and brain after either method of administration, but with important differences in uptake. Bioavailability based on appearance in arterial serum showed that about 23% and 14% of the intranasal administered doses of pregnenolone and progesterone, respectively, entered the blood. Brain levels were about two fold lower after intranasal administration for the two neurosteroids. With intranasal administration, brain levels of the two steroids did not vary over time (2–120 min), whereas brain levels were higher early (10 min or less) after i.v. administration. With i.v. administration, uptake by brain regions did not vary, whereas the olfactory bulb, hippocampus, and hypothalamus had high uptake rates after intranasal administration. Intranasal administration of prenenolone improved memory, whereas progesterone decreased anxiety, thus demonstrating that therapeutic levels of neurosteroids can be delivered to the brain by intranasal administration. The neurosteroids were rapidly degraded after i.v. or intranasal delivery...

‣ Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae

Briles, D.; Hollingshead, S.; Paton, J.; Ades, E.; Novak, L.; van Ginkel, F.; Benjamin Jr, W.
Fonte: Univ Chicago Press Publicador: Univ Chicago Press
Tipo: Artigo de Revista Científica
Publicado em //2003 Português
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Intranasal infection of mice with certain strains of capsular group 19 Streptococcus pneumoniae can result in focal pneumonia in the absence of bacteremia. Using this model of murine pneumonia, we demonstrated that immunization with recombinant forms of either pneumococcal surface protein A (PspA) or PdB (a genetically detoxified derivative of pneumolysin) elicited significant protection against focal pulmonary infection. This may be the first demonstration that a proposed vaccine antigen can protect against pneumococcal pneumonia. The best protection was obtained by immunizing mice with a mixture of PspA and PdB, indicating that the protection elicited by these antigens can complement each other. This result is in agreement with previous studies that used pneumococcal sepsis and nasal colonization models and demonstrate that the best protein vaccines for prevention of infection may be those that include more than one protection-eliciting pneumococcal protein.; David E. Briles, Susan K. Hollingshead, James C. Paton, Edwin W. Ades, Lea Novak, Frederik W. van Ginkel, and William H. Benjamin, Jr.

‣ Pancreatic β-cell function and immune responses to insulin after administration of intranasal insulin to humans at risk for type 1 diabetes; Pancreatic beta-cell function and immune responses to insulin after administration of intranasal insulin to humans at risk for type 1 diabetes

Harrison, L.; Honeyman, B.; Steele, C.; Stone, N.; Sarugeri, E.; Bonifacio, E.; Couper, J.; Coleman, P.
Fonte: Amer Diabetes Assoc Publicador: Amer Diabetes Assoc
Tipo: Artigo de Revista Científica
Publicado em //2004 Português
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48.261147%
OBJECTIVE: Mucosal administration of insulin retards development of autoimmune diabetes in the nonobese diabetic mouse model. We conducted a double-blind crossover study in humans at risk for type 1 diabetes to determine if intranasal insulin was safe, in particular did not accelerate beta-cell destruction, and could induce immune effects consistent with mucosal tolerance. RESEARCH DESIGN AND METHODS: A total of 38 individuals, median age 10.8 years, with antibodies to one or more pancreatic islet antigens (insulin, GAD65, or tyrosine phosphatase-like insulinoma antigen 2) were randomized to treatment with intranasal insulin (1.6 mg) or a carrier solution, daily for 10 days and then 2 days a week for 6 months, before crossover. The primary outcome was beta-cell function measured as first-phase insulin response (FPIR) to intravenous glucose at 0, 6, and 12 months and then yearly; the secondary outcome was immunity to islet antigens, measured monthly for 12 months. RESULTS: No local or systemic adverse effects were observed. Diabetes developed in 12 participants with negligible beta-cell function at entry after a median of 1.1 year. Of the remaining 26, the majority had antibodies to two or three islet antigens and FPIR greater than the first percentile at entry...

‣ Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children

Belshe, R.; Newman, F.; Anderson, E.; Wright, P.; Karron, R.; Tollefson, S.; Henderson, F.; Meissner, H.; Madhi, S.; Roberton, D.; Marshall, H.; Loh, R.; Sly, P.; Murphy, B.; Tatem, J.; Randolph, V.; Hackell, J.; Gruber, W.; Tsai, T.
Fonte: Univ Chicago Press Publicador: Univ Chicago Press
Tipo: Artigo de Revista Científica
Publicado em //2004 Português
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We evaluated a combination respiratory syncytial virus (RSV) and parainfluenza 3 virus (PIV3) live, attenuated intranasal vaccine for safety, viral replication, and immunogenicity in doubly seronegative children 6–18 months old. RSV cpts-248/404 and PIV3-cp45 vaccines were combined in a dose of 105 plaque-forming units of each per 0.5-mL dose and compared with monovalent vaccines or placebo. The virus shedding pattern of RSV was not different between monovalent RSV cpts-248/404 vaccine and combination vaccine. Modest reductions in the shedding of PIV3-cp45 vaccine virus were found after the administration of RSV cpts-248/404 and PIV3-cp45 vaccine, relative to monovalent PIV3 vaccine; 16 (76%) of 21 children given combination vaccine shed PIV3-cp45 versus 11 (92%) of 12 of those given monovalent PIV3 vaccine. Both vaccines were immunogenic, and antibody responses were similar between the monovalent groups and the combination group. Combined RSV/PV3 vaccine is feasible for simultaneous administration, and further studies are warranted.; Robert B. Belshe, Frances K. Newman, Edwin L. Anderson, Peter F. Wright, Ruth A. Karron,Sharon Tollefson, Frederick W. Henderson, H. Cody Meissner, Shabir Madhi, Don Roberton, Helen Marshall,Richard Loh...

‣ Evaluation of the dose-response relationship for intra-nasal oxymetazoline hydrochloride in normal adults

Taverner, D.; Bickford, L.; Shakib, S.; Tonkin, A.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Artigo de Revista Científica
Publicado em //1999 Português
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OBJECTIVES: To evaluate the dose-response relationship of increasing doses of oxymetazoline compared with placebo in normal subjects, and to determine the sensitivities of rhinomanometry, acoustic rhinometry and symptoms in discriminating between differing doses of oxymetazoline in normal subjects. METHODS: The study had a randomized, double-blind, placebo-controlled, parallel group, dose-response design. One hundred and twenty-five healthy volunteers with no nasal obstruction were randomized to administration of a single intra-nasal dose of oxymetazoline (6.25 microg, 12.5 microg, 25 microg or 50 microg) or placebo to each nasal cavity. Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Total minimum cross-sectional area (tMCA) and volume (tVOL) were measured by acoustic rhinometry. Symptoms of congestion (CON) were assessed on a visual analogue scale. RESULTS: The two highest doses of oxymetazoline produced a significant decrease in NAR compared with placebo (P = 0.015) but not between placebo and 12.5 microg or 6.25 microg. There was a dose-response relationship for tVOL, which increased significantly after all doses compared with placebo (P < 0. 001) and showed differences between 6.25-microg and 25-microg (P < 0. 014) and 12.5-microg and 50-microg (P < 0.05) doses. tMCA increased compared with placebo after all treatments (P = 0.028)...

‣ Effects of the route of estrogen administration on insulinlike growth factor-I, IGF binding protein-3, and insulin resistance in healthy postmenopausal women: results from a randomized, controlled study

Davis, S.; Stuckey, B.; Norman, R.; Papalia, M.A.; Drillich, A.; Bell, R.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
Relevância na Pesquisa
48.120103%
OBJECTIVE: Oral estrogen therapy suppresses insulin like growth factor I (IGF-I) levels, whereas conventional dose transdermal estradiol (E2) does not. However, it has been proposed that if sufficiently high serum E2 levels are achieved, nonoral E2 will also suppress serum IGF-I. The aim of the study was to investigate the effects of intranasal E2 with norethisterone (E2/NET) versus oral E2/NET acetate on IGF-I, IGF binding protein 3, and insulin resistance in postmenopausal women. DESIGN: This was a randomized, multicenter, double-blind, double-dummy trial. Postmenopausal women were randomized to receive either daily intranasal E2/NET (175 microg/275 microg) as a spray and a placebo tablet (n = 41) or oral E2/NET acetate (1 mg/0.5 mg) plus placebo intranasal spray (n = 41) for 1 year. Fasting plasma concentrations of IGF-I, IGF binding protein 3, glucose and insulin, glucose and insulin at 120 minutes post-glucose challenge, and the homeostasis model assessment for insulin resistance were assessed at baseline and after 52 weeks of treatment. RESULTS: The two groups were well matched for all clinical and biochemical parameters at baseline. There were no significant between-group differences for fasting and 120-minute glucose, insulin...

‣ C-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection

Ogunniyi, A.; Paton, J.; Kirby, A.; McCullers, J.; Cook, J.; Hyodo, M.; Hayakawa, Y.; Karaolis, D.
Fonte: Elsevier Sci Ltd Publicador: Elsevier Sci Ltd
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or pneumococcal surface protein A (PspA) before pneumococcal challenge, were investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of Streptococcus pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in a significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and a significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases.; http://www.elsevier.com/wps/find/journaldescription.cws_home/30521/description#description; Abiodun D. Ogunniyi...

‣ Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections

Alsharifi, M.; Furuya, Y.; Bowden, T.; Lobigs, M.; Koskinen, A.; Regner, M.; Trinidad, L.; Boyle, D.; Mullbacher, A.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
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Background Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that γ-ray inactivated flu virus can induce cross-reactive Tc cell responses. Methodology/Principal Finding Here, we report that intranasal administration of purified γ-ray inactivated human influenza A virus preparations (γ-Flu) effectively induces heterotypic and cross-protective immunity. A single intranasal administration of γ-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. Conclusions/Significance Intranasal γ-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections.; Mohammed Alsharifi, Yoichi Furuya, Timothy R. Bowden, Mario Lobigs, Aulikki Koskinen, Matthias Regner, Lee Trinidad, David B. Boyle and Arno Müllbacher

‣ Increased antigen specific T cell numbers in the absence of altered migration or division rates as a result of mucosal cholera toxin administration

Kaparakis-Liaskos, Maria; Tate, Michelle D.; Price, Jason D.; Pearse, Martin; Wijburg, Odilia L. C.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica Formato: 11 pages
Português
Relevância na Pesquisa
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Cholera toxin (CT) is a mucosal adjuvant capable of inducing strong immune responses to co-administered antigens following oral or intranasal immunization of mice. To date, the direct effect of CT on antigen-specific CD4(+) T cell migration and proliferation profiles in vivo is not well characterized. In this study, the effect of CT on the migration pattern and proliferative responses of adoptively transferred, CD4(+) TCR transgenic T cells in orally or intranasally vaccinated mice, was analyzed by flow cytometry. GFP-expressing or CFSE-labeled OT-II lymphocytes were adoptively transferred to naïve C57BL/6 mice, and mice were subsequently vaccinated with OVA with or without CT via the oral or intranasal route. CT did not alter the migration pattern of antigen-specific T cells, regardless of the route of immunization, but increased the number of transgenic CD4(+) T cells in draining lymphoid tissue. This increase in the number of transgenic CD4(+) T cells was not due to cells undergoing more rounds of cellular division in vivo, suggesting that CT may exert an indirect adjuvant effect on CD4(+) T cells. The findings reported here suggest that CT functions as a mucosal adjuvant by increasing the number of antigen specific CD4(+) T cells independent of their migration pattern or kinetics of cellular division.; Grant support was received from the National Health and Medical Research Council of Australia (NHMRC). OLW is a recipient of an R.D. Wright Career Development Award.