We compared the binding of [3H]-dexamethasone in cytosols prepared from atria and ventricles. The effects of steroid treatment and adrenalectomy on receptor concentration were measured in both male and female rats. In male rats the distribution of receptors was similar in atria and ventricles. In contrast, the atria of female rats in all treatment groups had twice the number of receptors as did the ventricles. Adrenalectomy in females resulted in receptor up-regulation, but dexamethasone treatment, which was effective in reducing binding in males and in the ventricles of females, failed to alter atrial binding in females. These results suggest that the atria of female rats may be more responsive than ventricles to the effects of circulating glucocorticoids.

ABSTRACT Purpose: Dexamethasone provides potent analgesic and antiemetic effects. Sevoflurane are associated with an increased incidence of postoperative nausea and vomiting (PONV) and delayed patient discharge compared to propofol. This study was designed to evaluate whether the prophylatic use of dexamethasone with sevoflurane could minimize the incidence of PONV and facilitate early recovery after outpatient anorectal surgery. Methods: Forty outpatients undergoing anorectal surgery were randomly assigned to receive either dexamethasone (5 mg IV; n=20) or an equal volume of saline (n=20) before the induction of anesthesia. Anesthesia was induced with sevoflurane 8% and N2O 67% in oxygen (at 6 L/min) followed by placement of laryngeal mask. Anesthesia was maintained with sevoflurane 2-4% end-tidal in combination with N2O 50% in oxygen 3 L/min. All patients were allowed to breathe spontaneously during the operation. The postoperative nausea and vomiting (PONV), VAS pain score and patient satisfaction were recorded. Results: The incidence of PONV and VAS pain score were significant lower in dexamethasone-treated patients compared with saline-treated ones. The time required for discharge was significantly shorter in dexamethasone-treated patients. Above all, the dexamethasone-treated patients expressed higher satisfaction index. There was no significant difference in recovery time for eye opening, response to commands, orientation, and ambulatory. Conclusions: The prophylactic administration of dexamethasone reduces the incidence of PONV andVAS pain score, promotes recovery to home readiness, and improves the satisfaction after the anesthesia with spontaneously breathing of sevoflurane through laryngeal mask in outpatients undergoing anorectal surgery.

Background: MY7 clinical trial compared dexamethasone plus melphalan (MD) vs. prednisone plus melphalan (MP) in multiple myeloma treatment and found no statistically significant difference in overall survival (OS) between the two groups. But, patients reacted to treatment differently. We aimed to identify patients who might have benefited from dexamethasone, and characterize them by their baseline demographic and clinical factors. Methods: First, the prognostic model for OS was developed on the MP arm. The estimated coefficients and baseline hazard were applied to the MD arm to derive martingale residuals (MR). Classification and regression tree analysis was done to identify independent predictive factors for OS and MR was used as response variable. All covariates in categorical shape were used as independent variables to develop the predictive model in MD arm. MP arm was divided accordingly. Subgroups with negative mean MR (survived > expected) were candidates for positive responders while those with positive mean MR (survived < expected) were candidates of negative responders. Mean MR in each subgroup and p values from comparison of OS (log rank test stratified by subgroups) were used to combine the appropriate subgroups as the positive responders or negative responders. Results: A total of 97 patients (42%) in MD arm were identified as positive responders and their OS (median of 44.5 months) was significantly longer than that (median of 33 months) in the corresponding subgroups in MP arm (HR = 0.56, 95% CI 0.4-0.8; p = 0.0014). All positive responders had three common baseline characteristics: aged ≤75 years, calcium concentration ≤2.6 mmol/L and Durie-Salmon stages 2 or 3. Among patients with ECOG performance status<2 those with either HGB≥100 mg/dl or HGB<100 mg/dl and WBC≥4,000 and <4 lytic bone lesions were categorized as positive responders. Also, among the patients with ECOG performance status≥2, males with >3 lytic bone lesions were positive responders. Negative responders (HR = 1.56, 95% confidence interval 1.1 – 2.2; p = 0.006) included patients aged >75 or aged ≤75 with calcium concentration >2.6 mmol/L or aged ≤75 with calcium concentration ≤2.6 mmol/L but had Durie-Salmon stage 1. Conclusions: Evaluation of the hypotheses validity warrants further studies. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2008-07-21 13:46:53.748

Thesis (M.S.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-05-25T13:40:41Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Tese_Anivaldo_Pereira_Duarte_Junior.pdf: 10191822 bytes, checksum: 646b55c8dd337a59ccd673e84bb95f92 (MD5) / Made available in DSpace on 2017-05-25T13:40:41Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Tese_Anivaldo_Pereira_Duarte_Junior.pdf: 10191822 bytes, checksum: 646b55c8dd337a59ccd673e84bb95f92 (MD5) Previous issue date: 2016-05-20 / CAPES / Carreadores lipídicos nanoestruturados (CLN) são sistemas coloidais que apresentam potencial de uso tópico. A utilização de constituintes de origem natural se apresenta como alternativa aos lipídios sintéticos, por isso a cera de carnaúba e óleo de pracaxi foram utilizados na preparação de CLN contendo dexametasona (DXM) com finalidade de tratar inflamações cutâneas. A caracterização do óleo foi realizada através da determinação da composição de ácidos graxos por cromatografia gasosa acoplada a detector de ionização de chama (CG-FID), densidade, viscosidade dinâmica e cinemática utilizando viscosímetro rotacional e EHL requerido. A elaboração de diagrama pseudoternário de fases (óleo/tensoativos/água), avaliação da mistura de cera/óleo por DSC e DRX, determinação do coeficiente de partição da DXM em óleo de pracaxi/água e a solubilidade em óleo de pracaxi também foram realizadas. A metodologia analítica por CLAE acoplada a detector UV para quantificação da DXM foi validada e um planejamento experimental fracionado seguido de composto central foi executado com objetivo de obter CLN em torno de 200nm, PDI ≤ 0,4 e maior eficiência de incorporação da DXM. O perfil e modelo cinético da liberação in vitro foi estabelecido e avaliou-se a penetração e/ou permeação cutânea in vitro da DXM em pele de orelha de porco utilizando células de difusão de Franz. O óleo de pracaxi contém 17% de ácido behênico e densidade de 0,90 −0,85g/cm3, viscosidade dinâmica de 65,75 −7,77mPa/s e cinemática de 72,99−9,09mm2/s entre 30−100℃. O EHL requerido do óleo de pracaxi foi 8,8 para Tween® 80 e Span® 60 (40:60) e o diagrama pseudoternário apresentou região de emulsão liquida leitosa com proporção de água a partir de 38% e a ocorrência de nanoemulsão (tamanho de 131,6 −258,3nm) com proporção de água de 87,5%. As misturas lipídicas apresentaram índice de cristalinidade de 71,88% e 31,93% em comparação com a cera de carnaúba. O método analítico apresentou parâmetros de validação adequados e a solubilidade da DXM em óleo de pracaxi foi de 190,16µg/mL. O log P da DXM em óleo de pracaxi/água foi de -0,4250. O CLN composto por DXM (0,15%), lipídios 10% (40% de óleo de pracaxi), tensoativos 5%, obtido com um ciclo de homogeneização e pressão de 600bar apresentou tamanho de 173,26nm, PDI 0,166 e eficiência de incorporação de DXM de 49,30%. O perfil cinético das formulações CLN-DXM e Gel DXM foi ajustado por modelo linear, com velocidades de 11,59 ± 0,49 µg/cm2/h e 2,42 ± 0,25µg/cm2/h, respectivamente. Entretanto, a formulação Gel CLNDXM apresentou perfil cinético melhor ajustado ao modelo de Higuchi, de acordo com a equação Q=15,64.t0,5 (2−12h)−18,432 (r 2 =0,9903). Os ensaios em pele não apresentaram absorção percutânea. A retenção da DXM no estrato córneo foi de 0,80 ± 0,13, 0,77± 0,15 e 0,16 ± 0,03µg/cm2 e na pele remanescente de 0,96± 0,17, 0,49± 0,18 e 0,13± 0,03 µg/cm2 para as formulações Gel CLN-DXM, Gel DXM e Creme DXM, respectivamente. A formulação Gel CLN-DXM promoveu penetração significativamente maior da DXM nas camadas profundas da pele em comparação às demais formulações, apresentando assim, possibilidade de exercer maior eficácia terapêutica da DXM. / Nanostructured lipid carriers (NLC) are colloidal systems that have potential for topical drug delivery. The use of natural lipids is an alternative to synthetic lipids and therefore carnauba wax and pracaxi oil were used to obtain dexamethasone-loaded NLC to treat skin inflammation. Pracaxi oil characterization was performed by fatty acids determination using gas chromatography coupled to a flame ionization detector (GC-FID). Density, kinematic and dynamic viscosities using a rotational viscometer and required HLB value were determined. Furthemore, pseudo ternary phase diagram (oil/surfactants/water), dispersed systems evaluation, wax/oil lipid mixture investigation by x-ray difraction and DSC, DXM partition coeficient in pracaxi oil/water and DXM solubility in pracaxi oil were determined. Analytical method for determining DXM content using HPLC coupled to an UV detector was validated. A fractional factorial and central composite designs to determine a CLN formulation with size around 200nm, PDI ≤ 0.4 and the best DXM incorporation efficiency was developed. The DXM in vitro release kinetic profile was evaluated and a kinetic model established. In vitro penetration and/or permeation in porcine ear skin using Franz diffusion cells was evaluated. Pracaxi oil contains 17% of behenic acid and presents a density, dynamic and kinematic viscosities, between 30 −100℃, of 0.90 −0.85g/cm3, 65.75−7.77mPa/s and 72.99−9.09mm2/s, respectively. Pracaxi oil required HLB was 8.8 using Tween® 80 and Span® 60 (40:60) surfactants. Pseudo ternary phase diagram presented a milky liquid emulsion region starting with 38% of water and the occurrence of nanoemulsion (size of 131.6 −258.3nm) at 87.5% of water. Lipid mixtures of pracaxi oil/carnauba wax showed crystallinity index varying from 71.88% to 31.93% comparedwithcarnaubawax.TheanalyticalmethodwassuitableforDXMdeterminations and the DXM solubility in pracaxi oil was 190.16µg/mL. The log P value of DXM in pracaxi oil/water was −0.4250. The CLN consisted of DXM 0.15%, 10% lipids (40% pracaxi oil), 5% surfactants was obtained with one homogenisation cycle and 600bar pressure, presented a particle size of 173.26nm, PDI of 0.166 and DXM encapsulation efficiency of 49.30%. The kinetic profile of CLN-DXM and DXM gel formulations was fitted by linear model, with speeds of 11.59 ± 0.49µg/cm2/hr, and 2.42± 0.25µg/cm2/hr, respectively. However, the CLN-DXM gel formulation presented kinetic profile best fitted to Higuchi model, according to the equation Q=15,64.t0,5 (2−12h)−18,432 (r 2 =0,9903). Skin penetration/permeation studies showed no percutaneous absorption. The formulations DXM-NLC/gel, DXM-gel and DXM cream showed DXM retention in stratum corneum layer of 0.80 ± 0.13, 0.77± 0.15 e 0.16± 0.03µg/cm2, and in remaining skin of 0.96± 0.17, 0.49 ± 0.18 e 0.13± 0.03µg/cm2, respectively. From these findings DXM-NLC/gel promoted significantly higher DXM penetration in deep skin in comparison with other DXM formulations, thus demonstrating a possible better DXM-NLC/gel therapeutic efficacy.

Orientador: Edson Antunes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T20:51:39Z (GMT). No. of bitstreams: 1 Datti_FernandaBeatrizBordonideGodoy_D.pdf: 2343891 bytes, checksum: 9aabaf2f218b6ed403cfd51c26441ed8 (MD5) Previous issue date: 2010 / Resumo: Estudos conduzidos em animais de experimentação e em humanos mostram que o período pré-natal é de suma importância para o desenvolvimento da prole. Estressores de qualquer natureza, se aplicados nesse período, podem promover alterações como baixo peso ao nascer, risco de intolerância à glicose, hipertensão arterial, dislipidemias e asma. O objetivo deste trabalho foi investigar o impacto da exposição de ratas prenhes a "estressores" que alteram a programação do eixo hipotálamo hipófise adrenal (HPA), como corticóides exógenos e endotoxina, sobre a resposta pulmonar alérgica. Para tanto, ratas Wistar prenhes foram submetidas à administração de dexametasona (0.1 mg/Kg, via s.c.; do 17° ao 20° dia gestacional) ou à administração de lipopolissacarídeo (LPS; 7 ?g/Kg, via i.p.; no 17° dia gestacional). A injeção de LPS foi realizada na ausência e na presença de tratamento com aminoguanidina (inibidor da sintase induzível de óxido nítrico; iNOS), oferecida na ingesta hídrica (50 mg/dia) a partir do 13° dia gestacional. Os descendentes adultos foram sensibilizados com ovalbumina (OVA; 200 g). Quatorze dias após a sensibilização, todos os animais foram desafiados com OVA (injeção intratraqueal contendo 2,5 mg/ml em 0,4 ml). Os lavados broncoalveolares (LBA), medula óssea e o sangue foram coletados 48 h após o desafio antigênico com OVA. Nossos resultados mostraram que a exposição pré-natal à dexametasona não altera o peso corpóreo dos descendentes fêmeas e machos ao nascer; porém, no desmame, fêmeas e machos apresentaram redução significativa no peso corpóreo (10,5% e 7,1% de redução, respectivamente). No LBA de fêmeas e machos observamos uma exacerbação de aproximadamente 120% e 128%, respectivamente, do influxo eosinofílico nos animais expostos prenatalmente à dexametasona e desafiados com OVA em comparação ao grupo controle. Nos protocolos de exposição pré-natal ao LPS, notamos um aumento do peso dos descendentes fêmeas e machos ao nascer, de aproximadamente 10,5% e 9,6%, respectivamente, em comparação com o controle. Este aumento foi ainda maior no desmame, quando fêmeas e machos prenatalmente expostos ao LPS estavam 19% e 22,5% mais pesados que os animais controle. Os animais prenatalmente expostos ao LPS, tanto fêmeas quanto machos, apresentaram redução significativa do influxo eosinofílico (aproximadamente 66,5% e 66,7%, respectivamente) no LBA dos animais desafiados com OVA em relação aos animais controle. O tratamento pré-natal com aminoguanidina restaurou o influxo eosinofílico, mantendo-o igual aos valores do grupo controle. No conjunto, nossos dados mostram que a exposição pré-natal à corticóides exógenos ou LPS são capazes de promover alterações na resposta inflamatória alérgica pulmonar na prole adulta, possivelmente por alterações na programação do eixo HPA / Abstract: Studies in experimental animals and in humans have showed that the prenatal period is critical for the development of the offspring; stress of any kind, if applied during this period, promotes definitive changes in late life. The aim of this study was to investigate the impact of exposure of pregnant rats to challenges that can alter the programming of the hypothalamic pituitary adrenal axis (HPA), such as exogenous steroids or endotoxin, on the pulmonary allergic inflammatory reaction to ovalbumin (OVA) challenge. Pregnant Wistar rats were submited to administration of either dexamethasone (0.1 mg / kg, sc; from 17th to 20th day of gestation) or lipopolysaccharide (LPS; 7 mg / kg, via ip; on the 17th gestation day). The LPS injection was performed in the absence and in the presence of treatment with aminoguanidine, given in tap water (50 mg / day) from the 13th gestation day. The adult offspring were sensitized by subcutaneous injection (0.15 ml) of a solution containing 200 g OVA adsorbed in aluminum hydroxide. Fourteen days after sensitization, all animals were challenged with an intratracheal injection of 0.4 ml saline containing OVA (2.5 mg/ml). The bronchoalveolar lavage (BAL), bone marrow and blood were collected 48 h after OVA challenge. Our data showed that prenatal exposure to dexamethasone did not alter the body weight of female and male offspring at birth, but at weaning, both sexes showed a significant litter weight reduction (10.5% and 7.1% reduction, respectively). In BAL fluid collected from females and males offspring, we observed an exacerbation (120% and 128%, respectively) of eosinophil influx in animals challenged with OVA and exposed prenatally to dexamethasone in comparison with control animals. The prenatal exposure to LPS caused an increase of body weight in male and female offspring at birth, approximately 10.5% and 9.6% respectively, in comparison with saline controls. This increase was higher at weaning, when females and males prenatally exposed to LPS were approximately 19% and 22.5% heavier than control animals. Animals prenatally exposed to LPS, both females and males, showed significant reductions of eosinophil influx (66.5% and 66.7% respectively) in the BAL fluid of animals challenged with OVA compared with control animals. Prenatal treatment with the nitric oxide synthesis inhibitor, aminoguanidine, restored the eosinophil influx to control values. Taken together, our data show that prenatal exposure to either exogenous corticoids or LPS are able to promote changes in the pulmonary allergic inflammatory response in adult offspring, possibly due to changes in HPA axis / Doutorado / Doutor em Farmacologia

Orientador: Eduardo Dias de Andrade / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-24T16:11:06Z (GMT). No. of bitstreams: 1 Brito_FabianoCapatode_D.pdf: 1226607 bytes, checksum: bf93752c3c24f16fc0b41670850b7e5d (MD5) Previous issue date: 2014 / Resumo: A analgesia preemptiva é um regime analgésico instituído previamente ao estímulo nocivo, com o objetivo de prevenir a hiperalgesia inflamatória e o subsequente estímulo que amplifica a dor no sistema nervoso central. Para aplicá-la na clínica cirúrgica odontológica, alguns fármacos com propriedades analgésicas e anti-inflamatórias têm sido avaliados, todavia com resultados ainda conflitantes. Por este motivo, propôs-se investigar, de forma comparativa, a analgesia preemptiva com dexametasona ou cetorolaco em cirurgias implantodônticas. Para tal, foram selecionados 33 indivíduos de ambos os gêneros, ASA I, que necessitavam de reabilitação bucal por meio da instalação de implantes dentários na região posterior da maxila ou mandíbula. Por ocasião da primeira ou da segunda intervenção, os voluntários foram tratados de maneira randomizada, com uma única dose de dexametasona 4 mg (via oral) ou cetorolaco 10 mg (via sublingual), administrada uma hora antes do início da cirurgia. A analgesia preemptiva foi avaliada pelo período de tempo compreendido entre o término do procedimento cirúrgico e o momento exato da tomada do primeiro comprimido do analgésico de resgate (paracetamol 750 mg), na fase pós-operatória. Os sujeitos da pesquisa também foram orientados a expressar a presença ou não de dor, e sua intensidade, no período das primeiras 12 horas pós-operatórias, na forma de uma escala analógica visual. Os dados foram tratados estatisticamente pelo teste de Wilcoxon, com nível de significância de 5%. Considerando o tempo decorrido entre a administração dos fármacos e a tomada do primeiro comprimido de analgésico, ou não, foi possível observar que não houve diferença estatisticamente significante (Wilcoxon, p = 0,0596) entre o cetorolaco (mediana = 3,6 h) e a dexametasona (mediana = 2,75 h). Também não houve diferença na incidência e na intensidade de dor no período das primeiras 12 horas pós-operatórias, se comparados os tratamentos (p = 0,7610). Concluiu-se que a dexametasona e o cetorolaco promovem analgesia preemptiva de forma similar em cirurgias de instalação de implantes dentários / Abstract: Preemptive analgesia is an analgesic regimen instituted prior to the noxious stimulus, in order to prevent inflammatory hyperalgesia and subsequent stimulus that amplifies pain in the central nervous system. To apply it in clinical dental surgery, drugs that have analgesic and anti-inflammatory properties have been studied, but the results are still conflicting. For this reason, we proposed to investigate, in a comparative way, preemptive analgesia with dexamethasone or ketorolac in surgical installation of dental implants. To this end, we selected 33 individuals of both genders, ASA I, who needed oral rehabilitation using dental implants in the posterior maxilla or mandible. On the occasion of the first or second intervention, the volunteers were treated randomly with dexamethasone 4 mg orally or ketorolac 10 mg sublingual on a single dose one hour before the intervention. Preemptive analgesia was assessed for the period of time between the end of the surgical procedure and the exact time of taking the first tablet of analgesic rescue medication (paracetamol 750 mg) postoperatively. The subjects were also instructed to express the presence or absence of pain and its intensity within the first 12 postoperative hours in the form of a visual analog scale. The data were statistically analyzed using the Wilcoxon test, with the significance level of 5%. Considered the mean time elapsed between drug administration and the first tablet, it was observed that there was no statistically significant difference (Wilcoxon, p = 0.0596) between ketorolac (median = 3, 6 h) and dexamethasone (median = 2.75 h). There was no difference in the incidence and intensity of pain during the first 12 postoperative hours, when the treatments (p = 0.7610) were compared. It was concluded that dexamethasone and ketorolac promote preemptive analgesia in a similar manner to the installation of dental implant surgery / Doutorado / Farmacologia, Anestesiologia e Terapeutica / Doutor em Odontologia

Glucocorticoids are widely used as anti-inflammatory and chemotherapeutic agents. However, prolonged use of glucocorticoids leads to osteoporosis. This study was designed to examine the mechanism of dexamethasone (DEX)-induced apoptosis in murine osteoblastic MC3T3-E1 cells. Total RNA was extracted from MC3T3-E1 cells treated with 10-7 M DEX for 6 h. DEX exerted a variety of effects on apoptotic gene expression in osteoblasts. Ribonuclease protection assays (RPA) revealed that DEX upregulated mRNA levels of caspases-1, -3, -6, -8, -11, -12, and bcl-XL. Western blot analysis showed enhanced processing of these caspases, with the appearance of their activated enzymes 8 h after DEX treatment. In addition, DEX also induced the activation of caspase-9. DEX elevated the levels of cleaved poly(ADP-ribose) polymerase and lamin A, a caspase-3 and a caspase-6 substrate, respectively. Expression of bcl-XL protein level was upregulated by DEX. Cytochrome c release was detected in the cytosol of DEX-treated cells. Furthermore, caspase-3 enzyme activity was elevated by 2-fold after DEX treatment for 7 h. Finally, early apoptotic cells were detected in cells treated with DEX for 3 h. Our results demonstrate that DEX-induced apoptosis involves gene activation of a number of caspases.

Bupivacaine is one of the amide type local anesthetics and is widely used for epidural anesthesia and blockade of nerves. Bupivacaine administration locally could result in neuron injury showing transient neurologic symptoms. Dexamethasone is a synthetic glucocorticoid and may exert cytoprotective properties against damage induced by some stimuli. In the present study, we evaluated the effects of dexamethasone on bupivacaine-induced toxicity in mouse neuroblastoma N2a cells. N2a cells were exposed to bupivacaine in the presence or absence of dexamethasone. After treatment, the cell viability, nuclear condensation, and lactate dehydrogenase levels were evaluated. Mitochondrial potential and Akt (threonine-serine protein kinase B) activation were also examined. In a separate experiment, we examined the effect of Akt inhibition by triciribine on cell viability following dexamethasone treatment. We also investigated whether dexamethasone could prevent lidocaine-induced neurotoxicity. Treatment of N2a cells with bupivacaine resulted in significant cell injury as evidenced by morphological changes, LDH leakage, and nuclear condensation. Pretreatment of the cells with dexamethasone significantly attenuated bupivacaine- and lidocaine-induced cell injury. Dexamethasone treatment prevented the decline of mitochondrial potential caused by bupivacaine and increased the levels of Akt phosphorylation. Importantly, pharmacological inhibition of Akt abolished the protective effect of dexamethasone against bupivacaine-induced cell injury. Our data suggest that pretreatment of neuroblastoma cells with dexamethasone exerts a protective effect on bupivacaine-induced neuronal cell injury. The mechanisms involve activating the Akt signaling pathway.

No description available.