Made available in DSpace on 2014-06-11T19:29:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-27Bitstream added on 2014-06-13T20:59:35Z : No. of bitstreams: 1 fioratti_eg_me_botfmvz.pdf: 886721 bytes, checksum: 138629ffeb23e3040d4251bc7120ebe1 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo deste estudo foi verificar a influência da adição de antiinflamatórios esteróides (AIES) ao diluidor seminal na motilidade e funcionalidade espermática e a eficiência da dexametasona na imunomodulação da resposta inflamatória após a cobertura. A dexametasona foi selecionada entre quinze diferentes AIES. Foram analisadas a motilidade (CASA), a integridade da membrana plasmática e acrossomal e o potencial da membrana mitocondrial dos espermatozóides nos momentos zero, 30, 60 e 120 minutos após a diluição. A intensidade da reação inflamatória provocada pelo sêmen foi mensurada em éguas resistentes e susceptíveis à endometrite persistente pós cobertura utilizando exame ultrassonográfico e citologia exfoliativa do útero, concentração de neutrófilos e de óxido nítrico do fluído uterino e taxa de recuperação embrionária. Dentre os AIES testados a dexametasona foi a que apresentou menor efeito deletério sobre as caracteísticas de motilidade e na morfofuncionalidade espermática. Quinze éguas resistentes e 15 susceptíveis à endometrite persistente após cobertura foram submetidas ao tratamento com dexametasona sistêmica e intra uterina adicionada ao diluidor de sêmen. As éguas susceptíveis apresentaram resposta inflamatória mais intensa durante as primeiras 8 horas após a inseminação artificial (p<0,05), porém, após 24 horas as concentrações de óxido nítrico foram semelhantes entre as éguas resistentes e susceptíveis, apesar das éguas susceptíveis manterem a reação inflamatória mais intensa até esse momento (p<0,05). As taxas de recuperação embrionária foram maiores para as éguas resistentes do que para as susceptíveis (p<0,05). Os tratamentos com dexametasona não se mostraram eficazes na imunomodulação da resposta inflamatória induzida pela cobertura / The objective of this study was to assess the influence of the addition of anti-inflammatory steroids (AIS) in the seminal extender in sperm viability and functionality, and efficiency of dexamethasone on immune modulation of inflammatory response after mating. Dexamethasone was selected from fifteen different AIS. Motility, membrane and acrosomal integrity and mitochondrial membrane potential of spermatozoa in moments 0, 30, 60 e 120 minutes after dilution were analyzed. The intensity of the inflammatory reaction caused by sperm was measured in resistant and susceptible mares using ultrasound examination and exfoliative cytology of the uterus, concentration of neutrophils and nitric oxide in uterine fluid and rate of embryo recovery. Among the AIS tested dexamethasone maintained the sperm motility parameters and did not show any deleterious effects on sperm structure and function (p>0.05). Fifteen mares resistant and 15 susceptible to post-breeding endometritis were subjected to treatment with dexamethasone systemic and intra uterine added to the semen extender. Susceptible mares showed more severe inflammatory response during the first 8 hours after artificial insemination (p<0.05), while 24 hours after mating the concentrations of nitric oxide were similar between resistant and susceptible mares, despite the fact that susceptible mares presented inflammatory reaction more intensive in this moment (p<0.05). The embryo recovery rates were higher for mares resistant compared to susceptible (p<0.05). Treatments with dexamethasone were not effective in the immunomodulation of the inflammatory response induced by mating

Orientador: Jose Roberto Bosqueiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-11T17:39:01Z (GMT). No. of bitstreams: 1 Quallio_Silvana_M.pdf: 957537 bytes, checksum: 0c375a9b9290585b85244a414a6ea02d (MD5) Previous issue date: 2008 / Resumo: Introdução e objetivos: O aumento nos níveis de glicose circulante é o principal estímulo para a secreção de insulina. A insulina se liga a receptores de membrana desencadeando diversas respostas celulares. Qualquer alteração na sensibilidade à insulina pode levar a disfunções fisiológicas como a resistência à insulina observada em pacientes diabéticos tipo 2 (T2DM). Experimentalmente, essa condição patológica pode ser mimetizada pela administração de altas doses de glicocorticóides, provendo assim um bom modelo para seu estudo. O objetivo do presente trabalho foi avaliar a plasticidade das ilhotas pancreáticas submetidas à variação na necessidade secretória de insulina por indução de resistência periférica ao hormônio por tratamento com dexametasona e posterior interrupção do tratamento. Métodos: Ratos wistar com 90 dias de vida foram tratados com dexametasona (1mg/kg, ip) por 5 dias consecutivos (DEX). Em outro grupo (DEX10), os animais foram tratados da mesma maneira e avaliados 10 dias após o último dia da administração de dexametasona. Ratos controle (CTL) receberam administração de NaCl 0,9% apenas. As ilhotas foram isoladas pelo método da colagenase. A expressão de proteínas foi feita por immunoblotting. As análises morfométricas foram realizadas microscopicamente. Resultados: O grupo DEX exibiu marcante resistência periférica à insulina, que foi revertida após o período de 10 dias no grupo DEX10. As ilhotas do grupo DEX apresentaram alterações funcionais e morfológicas como aumento da secreção de insulina estimulada por secretagogos, da área, da densidade e tendência de aumento na massa de células ß ao contrário do grupo DEX10. O conteúdo de proteínas relacionadas ao ciclo celular como a CD2 e CDK4 e a fosforilação da AKT aumentou em ilhotas do grupo DEX, mas retornou aos níveis do CTL em ilhotas DEX10. Conclusão: Estes resultados mostram a plasticidade do pâncreas endócrino haja vista a habilidade de se adaptar a situações que exigem maior ou menor demanda de insulina / Abstract: Introduction and aims: Insulin binds to plasma membrane receptors leading to a variety of cellular responses. Malfunction in any of the insulin cell signalling pathways in target tissues may lead to several conditions and diseases, like hyperglycemia, insulin resistance and type 2 diabetes mellitus (T2DM). These effects may be experimentally reproduced using high doses of glucocorticoids, providing thus a good model for the study of T2DM. The aims of this study were to evaluate the plasticity of pancreatic islets subject to variation on the need for insulin secretory induction of peripheral resistance to the hormone by treatment with dexamethasone and subsequent treatment interruption. Methods: Male wistar rats (90 days old) were treated with dexamethasone (1mg/kg, ip) for 5 consecutive days (DEX). In another group (DEX10), the animals were treated in the same way and assessed 10 days after the last day of administration. Control rats (CTL) received equivalent volume of vehicle. Protein expression was assayed trough immunoblotting. Morphometric analyses were done using a optical microscope and specific digital analysis programs. Results: DEX group showed marked peripheral insulin resistance, reverted after the recovering period in the DEX10 group. DEX islets showed functional and morphological changes, like increased insulin secretion, superficial area, population density, and a tendency for increase in the total mass content of beta cell. Cell cycle proteins CD2 and CDK4 and AKT phosphorylation were increased in the DEX group when compared to CTL group. All these effects were reverted in the group DEX10. Conclusions: These results show that the endocrine pancreas possess a plasticity regarding the capacity of pancreatic islets to adapt themselves to situations where a higher or lower demand for insulin is needed. / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / IntroduÃÃo: A mucosite induzida por antineoplÃsicos à um fator limitante na terapia anticÃncer. Mucosite à um termo clÃnico que descreve uma sÃndrome caracterizada por ulceraÃÃo da mucosa de todo o trato digestivo. O trato gastrintestinal à vulnerÃvel por causa da alta proliferaÃÃo e freqÃÃncia de renovaÃÃo celular. Assim, a mucosite intestinal resulta de eventos inflamatÃrios, que levam as alteraÃÃes de permeabilidade e trÃnsito intestinal e de alteraÃÃes na motilidade intestinal tanto na fase inflamatÃria, como na fase pÃs-inflamatÃria. Pentoxifilina (PTX) à um importante inibidor da sÃntese de citocinas, alÃm de apresentar efeito protetor sobre a mucosite oral por 5-FU em hamster. A dexametasona (DEXA) à um glicocorticÃide cujo principal efeito farmacolÃgico decorre de sua aÃÃo antiinflamatÃria e imunossupressora. Objetivos: Avaliar o efeito do tratamento com pentoxifilina ou dexametasona na resposta inflamatÃria e nas alteraÃÃes da motilidade digestiva associadas a mucosite intestinal experimental induzida por 5-FU. MÃtodos: Ratos Wistar machos (200 â 250g) foram tratados no d0 com 5-FU (150 mg/Kg, i.p. dose Ãnica) ou com 5-FU + PTX (90mg/Kg, s.c.) ou 5-FU + DEXA (2,5mg/Kg, i.p.). A PTX e a DEXA foram administradas meia hora apÃs a administraÃÃo de 5-FU no d0 e diariamente atà o sacrifÃcio. No d3 os animais foram sacrificados, amostras do duodeno, jejuno e Ãleo, foram removidas para avaliar a injÃria epitelial por morfometria, escores histolÃgicos, pela atividade de MPO e pela concentraÃÃo de GSH. Para avaliaÃÃo de citocinas amostras de duodeno foram retiradas e pelo mÃtodo de ELISA foi determinada a concentraÃÃo de TNF-&#61537; e IL-1&#61538; e pela imunohistoquÃmica foi observado a imunomarcaÃÃo. Jà na tÃcnica de esvaziamento gÃstrico os animais receberam o mesmo tratamento descrito anteriormente. Posteriormente, foram deixados em jejum de 18 horas do d2 para o d3. No d3, foram administrados 1,5 ml da soluÃÃo glicosada (5%) contendo vermelho de fenol (VF) a 0,75 mg/ml em cada animal. ApÃs 20 min, os animais foram sacrificados e submetidos a uma laparotomia mediana. O intestino delgado foi exposto e divido em 3 partes iguais: proximal, medial e distal. Com o auxÃlio de uma proveta contendo uma soluÃÃo de NaOH (100ml, 0,1N) o volume do estÃmago e dos segmentos do intestino delgado foram determinados. A absorbÃncia da amostra foi lida sob um comprimento de onda de 540 nm. Resultados: O tratamento com 5-FU foi capaz de induzir uma lesÃo intestinal com um importante comprometimento da barreira epitelial funcional com a presenÃa das seguintes alteraÃÃes: encurtamento acentuado das vilosidades intestinais, necrose parcial de criptas, vacuolizaÃÃo de cÃlulas, presenÃa de infiltrado mono e polimorfonucleares, produÃÃo de radicais livres com consumo de GSH, aumento na concentraÃÃo de TNF-&#61537; e IL-1 com maior imunomarcaÃÃo (no duodeno) e alteraÃÃes na motilidade digestiva. O tratamento com DEXA e PTX reduziu significativamente as lesÃes intestinais, com recuperaÃÃo da altura dos vilos, recuperaÃÃo da profundidade das criptas, diminuiÃÃo do infiltrado neutrofÃlico, aumento dos nÃveis de glutationa e reduÃÃo da concentraÃÃo de TNF-&#61537;, IL-1&#61538; com uma menor imunomarcaÃÃo. Contudo somente o tratamento com DEXA foi capaz de reverter o retarde do esvaziamento gÃstrico e do transito gastrintestinal. ConclusÃo: 5-FU induz mucosite intestinal em ratos com a participaÃÃo de TNF-&#61537; e IL-1&#61538;, a qual se associa com retarde no esvaziamento gÃstrico e no transito gastrintestinal. O tratamento com PTX ou DEXA foram capaz de reverter parte dos achados inflamatÃrios, entretanto, somente o tratamento com DEXA foi capaz de reverter parcialmente Ãs alteraÃÃes na motilidade digestiva associadas a mucosite por 5- FU em ratos. / Introduction: One of the most important limitation of antineoplasic chemotherapy is the intestinal mucositis. Mucositis is a clinical term wich describes a syndrome characterized for ulceration in the digestive tract. Gastrointestinal tract is vulnerable because it have elevated proliferation cellular renovation. Intestinal mucositis results in inflammatory events, that leads the alterations in permeability and gastrointestinal motility in the inflammatory phase, as in the post-inflammatory phase. Pentoxifylline (PTX) is important inhibitor of the cytokines synthesis, with a protective effect against 5-FU- induced oral mucositis in hamster. Dexamethasone (DEXA) is glucorticoide with anti-inflammatory and immunosuppressive effects. Aim: To evaluate the effect of the pentoxifylline or dexamethasone treatments in the inflammatory response and alterations of the gastrointestinal motility associate with 5-FU- induced intestinal mucositis. Methods: Male Wistar rats (200 â 250g) treated in d0 by 5-FU (150 mg/Kg, i.p. only dose) or 5-FU + PTX (90 mg/Kg, s.c.) or 5-FU + DEXA (2.5mg/Kg, i.p.). PTX or DEXA were administrated 30â after 5-FU, and then daily. In d3, animals were sacrificed, samples duodenum, jejunum and ileum were removed for assessment epithelial damage for morphometric, histological scores, MPO activity and GSH concentration. In order to evaluate the concentration of TNF-&#61537; and IL-1&#61538;, duodenum samples were removed and ELISA or imunohistoquimic for this cytocines were performed. In order to evaluated the gastrointestinal motility, animals received same treatment described previously, then were fasted for 18h of the d2 to d3. In d3 the animals were gavage-fed with a test meal and sacrificed 20 min later. Stomach and consecutive intestinal segments same (proximal, medial and distal) were obtained. Each segment was placed in a measuring cylinder and the volume measured by adding 100 mL of 0.1 NaOH. The absorbance of the sample was read at a 540 nm. Results: The treatment with 5-FU induced intestinal damage with an important disruption of the functional epithelial barrier and presence of these following alterations: shortening villus, partial necrosis crypts, vacuolated cells, presence of infiltrated mono and polymorphonuclears, production of free radicals with GSH consumption, increase in the concentration of TNF-&#61537; and IL-1&#61538; in the duodenum, and gastrointestinal dismotility. The treatment with DEXA and PTX significantly reduced the intestinal damage, with recovery of the high villus, depth of crypt, reduction of the neutrophil infiltration, increase of the levels of glutathione and reduction in the TNF-&#61537; and IL-1&#61538; concentrations. However, only the treatment with DEXA was able to reverse the delays gastric emptying and gastrointestinal transit induced by intestinal mucositis. Conclusion: 5-FU induces intestinal mucositis in rats with the participation of TNF-&#61537; and IL-1&#61538;. It associates with delayed gastric emptying and gastrointestinal transit. We conclude also that PTX or DEXA- treatments decreases the inflammatory response. On the other hand, only DEXA treatment reversed gastrointestinal dismotility associate with 5â FU- induced intestinal mucositis in rats.

Orientadores: Francisco Carlos Groppo, Eduardo Dias de Andrade / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-18T23:35:48Z (GMT). No. of bitstreams: 1 Silva_JulioCesarLeiteda_D.pdf: 4066006 bytes, checksum: ab7decd7e40b9d8792d9a6e478a205bb (MD5) Previous issue date: 2011 / Resumo: A análise das complicações pós-operatórias na remoção de terceiros molares retidos tem sido comumente usada e amplamente aceita como modelo para avaliar a eficácia dos vários fármacos analgésicos e anti-inflamatórios em humanos. Entretanto, ainda não existe consenso na literatura a respeito do melhor protocolo para o controle medicamentoso da dor e/ou inflamação nesse tipo de procedimento. Foi proposta deste estudo randomizado, duplo-cego e cruzado, observar e comparar a eficácia de dois anti-inflamatórios, um corticoide e um antiinflamatório não esteroide inibidor seletivo de COX-2 (dexametasona 8 mg e nimesulida 100 mg) respectivamente, por meio da medição da dor, do edema e da limitação da abertura bucal decorrentes de inflamação pós-exodontia de terceiros molares inferiores retidos. Para tanto, 30 voluntários de ambos os gêneros, entre 18 e 26 anos, sem patologias locais ou sistêmicas, exibindo terceiros molares inferiores retidos bilateralmente, com disposição similar e extração indicada, foram submetidos a cirurgias para remoção dos mesmos. Duas intervenções distintas foram realizadas, ambas no período da manhã, sempre pelo mesmo operador (cirurgião bucomaxilofacial) e separadas por um intervalo mínimo de 21 dias. Para uma exodontia, o voluntário recebeu um comprimido placebo uma hora antes do procedimento cirúrgico e 1 comprimido de 100 mg do anti-inflamatório nimesulida 10 minutos após o término da cirurgia e a cada 12 horas, por 3 dias. Para a exodontia seguinte o voluntário recebeu um comprimido de 8 mg do antiinflamatório dexametasona, por via oral, uma hora antes do início da intervenção cirúrgica e 1 comprimido placebo 10 minutos após a cirurgia e a cada 12 horas, por 3 dias. Após bloqueio do nervo alveolar inferior lingual e bucal com articaína a 4% com epinefrina 1:100.000 os procedimentos cirúrgicos foram realizados. Comprimidos de dipirona sódica 500 mg foram fornecidos como medicação de escape para controle da dor, anotando o dia e horário em que consumiram o medicamento, respeitando o intervalo de 6h entre as doses. Dados foram registrados no pré - operatório, 24 e 48 horas para edema e 72 e 168 horas para limitação da abertura bucal no pós-operatório. A dor foi avaliada por meio de uma escala analógica visual (EAV) em quadrados de onze pontos. A presença de limitação da abertura bucal e edema foi analisada, respectivamente, pela medição da distância interincisal e da distância do bordo inferior do lobo auricular-mento. Os resultados obtidos na EAV e a comparação do edema e limitação da abertura bucal no pré e pós-operatório foram submetidos ao teste de Wilcoxon ou teste t pareado, considerando o nível de significância de 5%. Os resultados mostraram que ambos os protocolos farmacológicos foram eficazes em cirurgias de terceiros molares inferiores retidos, bem como os efeitos das drogas dexametasona e nimesulida foram similares nos resultados para controle da dor, edema e limitação da abertura bucal / Abstract: The removal of impacted mandibular third molars has been a widely accepted model to study the efficacy of analgesics and anti-inflamatory properties of drugs in humans. However, there is no still consensus in the literature, as to the the best pharmacological protocol in order to control pain and/or inflammation after this kind of surgical procedure. The proposal of this double blind crossed-over randomized study was to observe and compare the efficacy of two antiinflammatory medicines, a corticoid (dexamethasone 8 mg), and, a non-steroid COX-2-selective inhibitor (nimesulide 100 mg), by measuring the levels of pain, edema and trismus, after the removal of impacted mandibular third-molars. For this study, 30 volunteers of both genders, aged between 18 and 26 years-old, without any local or systemic pathologies, and exhibiting impacted bilateral lower third molars in similar position and extraction recommended, were submitted to surgical removal of the teeth. Two surgical sessions, at least 21 days apart from each other were conducted in the mornings, always by the same surgeon. For one exodontia, the volunteer received a placebo pill an hour before the surgical procedure; ten minutes after the end of the surgery and every 12 hours thereafter, for 3 days, one 100 mg pill of the anti-inflammatory nimesulide was given. For the other surgery, the volunteer received an oral dose of 8mg of the anti-inflammatory dexamethasone, one hour before the surgery; 10 minutes after the surgery, and every 12 hours for the next 3 days, a placebo pill was administered. The anesthesic technique used was the blocking the lower alveolar, buccal and lingual nerves using articaine 4% with epinephrine 1:100.000. All volunteers were authorized to take analgesics, sodium dipyrone 500 mg four times daily, only in case of pain, while taking notes of the time and day when they took the medicine. Data was collected during pre-surgical period, and the 24 and 48 post-surgical hours to measure edema, and 72 and 168 hours for trismus. The pain was evaluated by Numerical Eleven Point Box Scale (BS-11). The presence of trismus and edema was respectively analyzed by the measurements of the inter-incisal distance, and by the lower part of the auricle lobe-pogonion distance. The results obtained in the VAS and the comparison of the edema and trismus levels in the pre and post-surgical periods were submitted to the Wilcoxon test, or paired t test, considering a 5% significance level. The results showed that both pharmacologic protocols are effective in retained lower molars exodontias. In addition, both antiinflammatory drugs (steroid and non-steroid), had a similar effect in the control of pain, edema and trismus / Doutorado / Farmacologia, Anestesiologia e Terapeutica / Doutor em Odontologia

Class of 2015 Abstract / Objectives: To assess the solubility and stability of tetracycline in compounded miracle mouthwash solutions over time, and at different temperatures (room temperature versus refrigerated) and pH (unaltered versus pH 7). Methods: Miracle mouthwash (MMW) solutions were compounded using tetracycline HCl capsules and 1:1 pseudo-dexamethasone elixir and diphenhydramine. High-performance liquid chromatography (HPLC) was used to measure the tetracycline concentrations in the MMW samples tested. Data on tetracycline crystal composition over time were also collected using powder x-ray diffraction, differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA). Results: For the tetracycline MMW solutions stored at room temperature, only 16% of the original tetracycline remained in solution after 24 hours, stabilizing at 65-81 mcg/mL on day 5 then decreasing further down to 45 mcg/mL by day 15. Similar results were obtained for the refrigerated tetracycline MMW solution (11% of original concentration after 5 days, with a decrease from 31-54 mcg/mL on day 5 to 22 mcg/mL on day 15). Tetracycline concentrations appeared to undergo a steeper decline in MMW solutions of pH 7 than in unadjusted MMW solutions (pH 4.68). All MMW samples exhibited a conversion from tetracycline HCl to tetracycline hexahydrate. Conclusions: Tetracycline solubility decreases rapidity in MMW within 24 hours of compounding regardless of temperature. MMW solutions at pH 7 may have further reduced solubility. Stability decreases at a stable rate from tetracycline HCl to tetracycline hexahydrate.

O estudo investigou a influência do fator de transformação de crescimento beta1 (TGFb1) sobre células osteogênicas induzidas com fatores mineralizantes (dexametasona Dex), comparando a viabilidade e a proliferação celular, a mineralização, e a expressão de proteínas não colágenas da matriz osteopontina (OPN), sialoproteína óssea (BSP) e fibronectina (FN). A morfologia foi examinada por microscopia eletrônica de transmissão (MET). O TGFb1 diminuiu a viabilidade e a proliferação celular, mesmo com Dex. A mineralização da matriz foi positivo apenas no grupo tratado com Dex, e negativo nos grupos tratados TGFb1 e TGFb1+Dex. OPN e BSP não foram imunoreativas apenas para o controle negativo, já a FN foi imunoexpressa em todos os grupos. A mineralização foi confirmada, tanto no controle positivo quanto no tratado com Dex, e alterações morfológicas foram observadas nas células tratadas com TGFb1 e TGFb1+Dex, através da MET. Esse estudo mostrou que TGFb1 inibe a mineralização, alterando a viabilidade e proliferação, bem como a morfologia celular, mesmo quando tratadas com Dex. / The study investigated the influence of transforming growth factor beta1 (TGFb1) on osteogenic cells induced with mineralizing factors (dexamethasone Dex), comparing the viability and proliferation cellular, the formation of mineral nodules in vitro, and the expression of the noncollagenous matrix proteins osteopontin (OPN), bone sialoprotein (BSP), and fibronectin (FN). The morphology was examined by transmission electron microscopy (TEM). The TGFb1 decreased the viability and proliferation cellular, even when combined with Dex. The mineralization of matrix was positive only in the group treated with Dex, and negative in the groups treated with TGFb1 and TGFb1+Dex. OPN and BSP were not immunoreactive only negative, already the FN was immunoreactive in all groups.The mineralizing was confirmed in the positive control and Dex, through TEM. Some morphological changes were seen in cells treated with TGFb1 and TGFb1+Dex. This study showed that TGFb1 inhibits the mineralization, changing the viability, proliferation and cell morphology, even when treated with Dex.

Orientador: Francisco Leydson Formiga Feitosa / Banca: Flávia de Almeida Lucas / Banca: Vanessa Veronese Ortunho / Resumo: Este trabalho teve como objetivo mensurar a produção de hidroperóxidos e a capacidade antioxidante do plasma de cabras e seus cabritos, por meio do teste d-ROMs (Reactive Oxygen Metabolites) e BAP (Biological Antioxidant Potential), após as cabras serem submetidas a diferentes protocolos de corticoterapia antenatal, os animais foram aleatoriamente alocados em quatro grupos experimentais: grupo I - constituído por quatro cabras e sete cabritos, com uma única dosagem de 20 mg de dexametasona, por via IM/SID, dois dias antes da cirurgia eletiva (139 dias); grupo II - composto por quatro cabras e seis cabritos utilizando a dosagem de 2 mg de dexametasona, dos 133 aos 136 dias; 4 mg dos 137 aos 138; e 20 mg aos 139 dias de prenhes, por via IM/SID; grupo III - constituído por quatro cabras e sete cabritos, com dosagem de 16 mg de dexametasona aos 139, com doses repetidas a cada 12 horas até a cirurgia eletiva, por via IM/BID, e grupo IV - composto por quatro cabras e seis cabritos utilizando a dose de 4, 8, 16 e 20 mg de dexametasona, por via IM/SID, aos 137, 138, 139, 140 dias de gestação, respectivamente. Para analisar d-ROMs e BAP foram feitas coletas de sangue nas cabras por punção da veia jugular aos 15 minutos (M15) após o parto, e nos cabritos foram realizadas as coletas de sangue por punção da veia jugular nos respectivos momentos com referência ao nascimento de cada neonato: 15 minutos (M15), 24 horas (M24) e 48 horas (M48). / Abstract: The objective of this work was to measure the production of hydroperoxides and the antioxidant capacity of goats and their goats by means of the d-ROMs test (Reactive Oxygen Metabolites) and BAP (Biological Antioxidant Potential), after the goats were submitted to different protocols of antenatal corticosteroid therapy, the animals were randomly assigned to four experimental groups: group I - consisting of four goats and seven goats, with a single dose of 20 mg of dexamethasone, IM / SID, two days before elective surgery (139 days); group II - composed of four goats and six goats using the dosage of 2 mg dexamethasone, from 133 to 136 days; 4 mg of 137 to 138; and 20 mg at 139 days of pregnancy, by IM/SID; group III - consisting of four goats and seven goats, with a dose of 16 mg of dexamethasone at 139, with repeated doses every 12 hours until elective surgery, by IM/BID, e group IV - composed of four goats and six goats using the dose of 4, 8, 16 and 20 mg dexamethasone, by IM / SID route, to the 137, 138, 139, 140 days of gestation, respectively. Blood samples were taken from the goats by puncture of the jugular vein at 15 minutes (M15) after calving and the kidneys were collected by puncturing the jugular vein at the respective moments with reference to the birth of each neonate: 15 minutes (M15), 24 hours (M24) and 48 hours (M48). / Mestre

Background and Purpose. Iontophoresis is a process that uses bipolar electric fields to propel molecules across intact skin and into underlying tissue. The purpose of this study was to describe and experimentally examine an iontophoresis drug delivery model. Subjects and Methods. A mechanistic model describing delivery was studied in vitro using agarose gels and was further tested in vivo by evaluation of cutaneous vasoconstriction following iontophoresis in human volunteers. Results. In vitro cathodic iontophoresis at 4 mA and 0.1 mA each delivered dexamethasone/dexamethasone phosphate (DEX/DEX-P) from a 4-mg/mL donor solution to a depth of 12 mm following a 40 mA·minute stimulation dosage. Delivery of DEX/DEX-P to at least the depths of the vasculature in humans was confirmed by observation of cutaneous vasoconstriction. This cutaneous vasoconstriction was longer lasting and greater in magnitude when using low-current, long-duration (∼0.1 mA) iontophoresis compared with equivalent dosages delivered by higher-current, shorter-duration (1.5-4.0 mA) iontophoresis. Discussion and Conclusion. From data gathered with the gel model, the authors developed a model of a potential mechanism of drug depot formation following iontophoresis. The authors believe this drug depot formation to be due to exchange of drug ions for chloride ions as the ionic current carriers. Furthermore, diffusion, not magnitude of current, appears to govern the depth of drug penetration. Although the authors did not address the efficacy of the drug delivered, the results of human experiments suggest that current magnitude and duration should be considered as factors in treating musculoskeletal dysfunctions with iontophoresis using DEX/DEX-P at a concentration of 4 mg/mL. [Anderson CR, Morris RL, Boeh SD, et al. Effects of iontophoresis current magnitude and duration on dexamethasone deposition and localized drug retention.

No description available.

Study Design: Controlled laboratory study. Objectives: To determine the time course of dexamethasone sodium phosphate (Dex-P) iontophoresis delivery to underlying tissues using microdialysis. Background: The efficacy of iontophoresis at delivering Dex-P through the skin is unknown in humans because of the lack of minimally invasive measurement techniques. Methods: Sixty-four healthy male participants (age = 24.4 ± 3.3 yrs, height = 71.8 ± 2.5 in, weight = 181.8 ± 26.1 lbs) were randomly assigned into one of six groups: 1) 1 mA current, 1 mm probes depth ; 2) 1 mA current, 4 mm probes depth; 3) 2 mA current, 1 mm probes depth; 4) 2 mA current, 4 mm probes depth; 5) in vivo retrodialysis; and 6) skin perfusion flowmetry. Microdialysis probes assess the combined recovery (Dextotal) of Dex-P, dexamethasone (Dex) and its metabolite. In vivo calibration of the microdialysis probes occurred via retrodialysis. Laser Doppler flowmetry assessed skin perfusion. Results: There was no difference of Dextotal between current intensities (P = 0.99) but a greater amount of Dextotal was recovered by the 1 mm probe (P < 0.0001) compared to the 4 mm probe. Peak means for the 1 and 2 mA at 1 mm were 10.8 ± 8.1 and 7.7 ± 5.5 μg/ml and at 4mm being 2.0 ± 0.8 and 1.3 ± 0.9 μg/ml, respectively. Skin perfusion rapidly increased during both current intensity treatments, but significantly decreased before the conclusion of the 1 mA treatment (P < 0.0001). Peak skin perfusion was 741.4 ± 408.7% and 711.6 ± 260.8% baseline for 1 and 2 mA intensities, respectively. Conclusion: Iontophoresis delivery of Dex-P was successful measured in vivo through human skin. Significant concentrations of Dextotal were found regardless of current intensity. Though current induced vasodilation occurred, it did not significantly affect the tissue accumulation of Dextotal.