Effect of angiotensin II and losartan on the phagocytic activity of peritoneal macrophages from Balb/C mice

Angiotensin II (AII), a product of rennin-angiotensin system, exerts an important role on the function of immune system cells. In this study, the effect of AII on the phagocytic activity of mouse peritoneal macrophages was assessed. Mice peritoneal macrophages were cultured for 48 h and the influence of different concentrations of AII (10-14 to 10-7 M) and/or losartan, 10-16 to 10-6 M), an AT1 angiotensin receptor antagonist, on phagocytic activity and superoxide anion production was determined. Dimethylthiazoldiphenyltetrazolium bromide reduction and the nucleic acid content were used to assess the cytotoxicity of losartan. A stimulatory effect on phagocytic activity (P < 0.05) was observed with 10-13 M and 10-12 M AII concentrations. The addition of losartan (up to10-14 M) to the cell cultures blocked (P < 0.001) the phagocytosis indicating the involvement of AT1 receptors. In contrast, superoxide anion production was not affected by AII or losartan. The existence of AT1 and AT2 receptors in peritoneal macrophages was demonstrated by immunofluorescence microscopy. These results support the hypothesis that AII receptors can modulate murine macrophage activity and phagocytosis, and suggest that AII may have a therapeutic role as an immunomodulatory agent in modifying the host resistance to infection.16717

Effect Of Angiotensin Ii And Losartan On The Phagocytic Activity Of Peritoneal Macrophages From Balb/c Mice.

Angiotensin II (AII), a product of rennin-angiotensin system, exerts an important role on the function of immune system cells. In this study, the effect of AII on the phagocytic activity of mouse peritoneal macrophages was assessed. Mice peritoneal macrophages were cultured for 48 h and the influence of different concentrations of AII (10(-14) to 10(-7) M) and/or losartan, 10(-16) to 10(-6) M), an AT1 angiotensin receptor antagonist, on phagocytic activity and superoxide anion production was determined. Dimethylthiazoldiphenyltetrazolium bromide reduction and the nucleic acid content were used to assess the cvtotoxicity of losartan. A stimulatory effect on phagocytic activity (P < 0.05) was observed with 10(-13) M and 10(-12 M) AII concentrations. The addition of losartan (up to10(-14) M) to the cell cultures blocked (P < 0.001) the phagocytosis indicating the involvement of AT1 receptors. In contrast, superoxide anion production was not affected by AII or losartan. The existence of AT1 and AT2 receptors in peritoneal macrophages was demonstrated by immunofluorescence microscopy. These results support the hypothesis that AII receptors can modulate murine macrophage activity and phagocytosis, and suggest that AII may have a therapeutic role as an immunomodulatory agent in modifying the host resistance to infection.99167-7

Free 2-propen-1-amine derivative and inclusion complexes with beta-cyclodextrin: scanning electron microscopy, dissolution, cytotoxicity and antimycobacterial activity

Inclusion complexes and physical mixtures of isomeric mixture of E/Z (50:50) of 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-bromophenyl)-N,N-dimethyl-2-propen-1-amine (BBAP) and beta-cyclodextrin (beta-CD) in the molar proportion of 1:1 and 1:2 were analyzed by scanning electron microscopy. The dissolution behavior of BBAP and of the inclusion complexes were also evaluated for six hours. By scanning electron microscopy (SEM), it was possible to observe an inclusion complex formed between BBAP and beta-CD by co-evaporation, either in the molar proportion of 1:1 or 1:2. In the physical mixtures, no complex was observed as previously detected by physicochemical analysis. The dissolution studies showed that the inclusion complexes BBAP/beta-CD 1:1 and 1:2 released respectively 49.07 &plusmn; 1.48 and 40.26 &plusmn; 3.90% of BBAP during six hours. Free BBAP was less soluble than the inclusion complex and reached 9.00 &plusmn; 0.75% of dissolution. Biological assays, such as cytotoxicity to J774 macrophages and to a permanent lung fibroblast cell line (V79), indicated that the BBAP does not exhibit any additional toxic effect with the beta-CD complexes. However, the complexes were less cytotoxic to V79 cells than the free form. The BBAP/beta-CD inclusion complexes were more effective (MIC) than the free compound on several mycobacteria strains. Similar behavior was observed for BBAP/beta-CD complexes and rifampicin, a front-line antitubercular drug, on M. tuberculosis H37Rv growing inside J774 macrophages.Complexos de inclusões e misturas físicas contendo mistura isomérica E/Z (50:50) de 3-(4'-bromo-[1,1'-bifenil]-4-il)-3-(4-bromofenil)-N,N-dimetil-2-propen-1-amina (BBAP) e beta-ciclodextrina (b-CD) nas proporções molares de 1:1 e 1:2 foram analisados por microscopia eletrônica de varredura (SEM). O perfil de dissolução do BBAP e dos complexos de inclusões foram também avaliados durante 6 horas. Por microscopia eletrônica de varredura foi possível observar os complexos de inclusões formados entre BBAP e beta-CD por co-evaporação nas proporções molares de 1:1 e 1:2. Como previamente detectado pela caracterização físico-química, na mistura física não se observou a presença de complexo de inclusão. Os estudos de dissolução mostraram que os complexos de inclusões 1:1 e 1:2 liberaram, respectivamente 49.07 &plusmn; 1.48 e 40.26 &plusmn; 3.90% de BBAP durante 6 horas. BBAP na forma livre foi menos solúvel que os complexos de inclusões e atingiu 9.00 &plusmn; 0.75% de dissolução. Os ensaios de citotoxicidade em macrófagos J774 e em uma linhagem de células fibroblásticas de pulmão (V79) indicaram que o BBAP não exibiu efeito tóxico adicional quando complexado com beta-CD. Entretanto, os complexos de inclusões foram menos tóxicos para células V79 que BBAP na forma livre. Os complexos de inclusões BBAP/beta-CD foram mais efetivos (CIM) que o composto livre em várias cepas de micobactérias. Resultados semelhantes foram observados sobre M. tuberculosis H37Rv intracelular para os complexos de inclusões BBAP/b-CD e rifampicina, uma droga anti-tuberculose de primeira linha.682689Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Herregårde – fornyere på landet? Gram Slot A/S mellem oplevelsesøkonomi og kulturarv

Denne artikel tager udgangspunkt i en opfattelse af, at historiske bygninger og kulturlandskaber kan medvirke til at skabe dynamik og fornyelse i lokalsamfund på landet præget af stilstand og tilbagegang. Eksempelvis var Fonden Realdania’s kampagne “Fremtidens Herregård” begrundet i et udtalt ønske om, at herregårdene kunne bidrage til regional udvikling på landet. Undersøgelser af kommercielle aktiviteter og oplevelsesøkonomi på Gram Slot A/S og andre danske herregårde vil demonstrere, på hvilke måder herregårdenes fortidige virkelighed finder anvendelse i nutidig virksomhedsdrift. Analyserne fører frem til en principiel diskussion af, i hvilket omfang – og med hvilke formål – kulturarv kan fungere som en relevant ressource for lokal og regional udvikling.SummaryCommercial heritage management at Gram Slot A/SIn recent decades, a substantial number of Danish country houses [da: “herregårde”] have explored business opportunities within the so-called “experience economy”. Privately owned country houses comprise a unique field of investigation, because these estates constitute both a shared cultural heritage and modern business ventures. In their efforts to generate income to uphold the country house and estate, owners and managers welcome visitors onto the estate and into the country house. Paying visitors are invited to “experience the country house” as venues for, among other things, weddings, parties, conferences, concerts, Christmas fairs, historical festivals, team-building, golf and tourism. This article comprises an analysis of commercial offerings and visitor practices at Gram Slot A/S, a Danish country house in southern Jutland operating as a private limited company since 2007. Gram Slot A/S produces organic food such as milk, oatmeal and potatoes as well as tourist services like fairs, dinner parties and holiday visits. Guided tours in the country house are provided to visitors with interpretations of Grams’ history as well as the present business operations. An analysis of six markedly different guided tours at Gram showed how different guides and different audiences could result in surprising shifts of perspective. Gram was variously presented as a historical country house, an innovative family business, an organic farm, a regional centre and a place of unique aesthetic qualities. The guided tours created a strong narrative that presented Gram as a place of past, present and future – a reminder that new activities may also create new history and new meaning(s) to country houses and other heritage sites. Through a presentation of various understandings of “cultural heritage” the article discusses commercial offerings and “experiences” in heritage management. The analysis shows that commercial heritage management may help bring revenue for conservation and provide historical “feeling” and a sense of place to visitors and to local and national communities. However, by academic standards historical representations are often flawed and rarely adds to historical understanding. In the final analysis, the article advocates a pragmatic view on cultural heritage management, in which country houses by adapting to new challenges – as cultural heritage as well as contemporary business – may create new meaning to historical buildings and thereby offer a different and rewarding view on how we relate to our past

Meta-analysis : study of effectiveness of drug therapy with molecular target for treatment of renal tumor metastatic

Orientadores: Wagner Eduardo Matheus, Ubirajara FerreiraTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Atualmente existem diferentes agentes para o tratamento do câncer renal avançado. O objetivo principal desse trabalho foi realizar revisão sistemática com meta-análise dos estudos clínicos randomizados que compararam: sorafenibe, sunitinibe, bevacizumabe, temsirolimus e everolimus ao interferon-?. Para isto foi realizada revisão sistemática da literatura em diferentes bancos de dados: EMBASE, LILACS e PUBMED, identificando estudos clínicos randomizados que compararam as terapias alvo moleculares (TAM) disponíveis versus interferon-alfa para tratamento de pacientes com câncer renal avançado. Para o tratamento de 1a linha foram encontrados 10 estudos que avaliaram as terapias com sunitinibe, sorafenibe, bevacizumabe e temsirolimus; e três estudos que avaliaram o sorafenibe e everolimus como tratamento de 2a linha. O Risco Relativo (RR) da sobrevida livre de progressão (SLP) dos estudos de 1a linha foi de 0.83, intervalo de confiança (IC) [0.78-0.87] com I2= 94% e p<0.00001. Os melhores resultados foram: o estudo do sunitinibe, 0.38, IC [0.25-0.58], do bevacizumabe com RR de 0.62, IC [0.47-0.83] e do temsirolimus, 0.78, IC [0.70-0.87]. A meta-análise não demonstrou benefício quanto à sobrevida global (SG), no tratamento de 1a linha com sunitinibe e temsirolimus. Os tratamentos de 1ª linha com sorafenibe e bevacizumabe não associaram benefícios clínicos significativos. Não foi possível realizar meta-análise nos estudos do tratamento de 2a linha, pois, as populações eram diferentes. Logo, para o tratamento de 1a linha, sunitinibe e temsirolimus foram a terapias mais efetivas, quanto a SLP. No tratamento de 2a linha, o sorafenibe e everolimus foram relacionados à melhora da SLP. Em todos os estudos de 1a linha os pacientes não apresentaram melhora de SG e a qualidade metodológica não foram adequadas, portanto esses resultados devem ser analisados com cautelaAbstract: Currently, there are different agents for the treatment of advanced kidney cancer. The main aim of this study was to perform a systematic review and meta-analysis of randomized clinical trials that compared: sorafenib, sunitinib, bevacizumab, temsirolimus and everolimus. It was performed a systematic review of the literature in different databases: EMBASE, LILACS and PubMed, identifying randomized clinical trials that compared the available therapies target cells versus alpha-interferon for the patient treatments with advanced kidney cancer. For the treatment of first-line were found 10 studies that evaluated the therapy with sunitinib, sorafenib, bevacizumab and temsirolimus and three studies evaluating sorafenib and everolimus as a treatment second-line. The relative risk of progression free survival of first line studies was 0.83, confidence interval (CI) [0.78-0.87] with I2 = 94% and p <0.00001. The best results were: the study of sunitinib, 0.38, CI [0:25 to 0:58], bevacizumab with RR of 0.62, CI [0.47-0.83] and temsirolimus, 0.78, CI [0.70-0.87]. The meta-analysis showed no benefit on overall survival in first-line treatment with sunitinib and temsirolimus. The first-line treatment with sorafenib and bevacizumab not associated significant clinical benefits. Unable to perform meta-analysis on studies of second-line treatment, because the cohorts were different between them. For the treatment of first-line, sunitinib and temsirolimus were more effective therapies, as the progression free survival (PFS). In the second line treatment, sorafenib and everolimus was associated with improved PFS. In these studies, patients showed no improvement in overall survival (OS) and methodological quality were not adequate, so these results should be analyzed with cautionDoutoradoFisiopatologia CirúrgicaDoutora em Ciência

Evaluation of the efficiency of a plasma sterilizater in the inactivation of Pseudomonas fluorescens

Orientador: Marcelo CristianiniDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de AlimentosResumo: Um dos problemas que enfrenta a indústria de laticínios é a recontaminação do leite decorrente da formação de biofilmes em tanques de armazenamento e trocadores de calor. A tecnologia de esterilização de materiais por gás plasma tem sido utilizada com sucesso na esterilização de instrumentos cirúrgicos, oftálmicos e dentários. Os objetivos deste trabalho foram avaliar a eficiência de um sistema de esterilização a gás plasma sob células de Pseudomonas fluorescens aderidas em placas de aço inoxidável utilizando o leite como substrato. Foram avaliadas as variáveis tempo de pré plasma, tempo de exposição ao plasma e potência do mesmo na remoção do biofilme. As placas de aço inoxidável com a bactéria aderida foram submetidas a um tratamento com gás plasma, que foi formado a partir de um produto comercial composto por ácido peracético, peróxido de hidrogênio e ácido acético. Dois sistemas modelo foram utilizados para simular a formação de biofilmes de Pseudomonas fluorescens, um dinâmico e outro estático, simulando trocadores de calor e tanques de armazenamento, respectivamente. Através do modelo estático foi possível obter contagens acima de 105 UFC por placa de aço inoxidável, mesmo após três ciclos de lavagem das placas em água estéril sob agitação. Foi observado um efeito positivo na inativação de P. fluorescens em função do tempo de pré-plasma do sanificante. Exposições acima de 7 minutos foram capazes de produzir reduções superiores a dois ciclos logarítmicos na inativação do microrganismo. Através de um planejamento experimental fatorial 23 foi demosntrado que as variáveis tempo de pré-plasma, tempo de exposição ao plasma e potência do plasma apresentaram efeitos positivos na inativação de Pseudomonas fluorescens. O tempo de exposição (min.) apresentou o maior efeito na destruição da bactéria; mas sendo um pouco superior à potência do plasma (w)Abstract: One of the problems that food industry is facing is the milk recontamination through biofims formation on storage tanks and heat exchanger. The technology of sterilization for materials through gas plasma has been used with succesfull for cirurgycal, ophathalmic and dentistry equipment. The goals of this work was to evaluate the efficiency of a gas plasma sterilization system on Pseudomonas fluorescens cells adhered on stainless steel plates using milk as substrate. Time of pre plasma, plasma exposition and potency (Watts) were evaluated as independent variables on cell destruction. The stainless steel plates were submitted to gas plasma treatment originated from a commercial product composed of peracetic acid, hydrogen peroxide and acetic acid. Two model systems were used to simulate a biofilm formation of Pseudomonas fluorescens, one dynamic and one static, in order to simulate heat exchangers and storage tanks, respectively. Through static model it was possible to get counts over 105 UFC/plate after washing three times using sterile water under stirring conditions. It was observed a positive effect on P. fluorescens inactivation by pre-plasma in a time dependent way. Expositions over seven minutes were capable to produce reductions higher than two logarithmic cycles on microorganism inactivation. A 23 factorial design indicated that the pre-plasma time, time exposition and potency showed positive effects on Pseudomonas fluorescens inactivation. Time exposition (min) was the most effective variable on bacteria destruction, being a little higher than plasma potency (w)MestradoMestre em Tecnologia de Alimento

Sìntese, Propriedades Tripanossomicidas E Toxicidade De P-bromobifenil X-metanonas (x=n-metil-3-indolila E Furanila) E /3-4(4'-bromo (1,1 -bifenil)-4-il)-3-(4-x)-n,n,dimetil-2-propen-1-aminas (x=n-metil-3-indolila, Furanila)=.

Trata-se de uma metodologia para síntese de p-bromobifenil X-metanonas (X = N-Metil-3-Indolila e Furanila) e de 3-(4’-bromo[1,1’-bifenil]-4-il)-3(4-X)-N, N-dimetil-2-propen-1amina (X = N-Metil-3-Idolila, Furanila) e a utilização das alilaminas como tripanossomicidas. A toxicidade e citotoxidade por vários métodos para ambas séries foram medidos. Foram obtidos os valores de IC50 para o furanila atuando sobre as formas tripomastigota, amastigotas e epimastigotas do Trypanosoma Cruzi.BR9805381 (A)A61K31/12A61K31/4045C07C211/26C07C211/29C07C229/38C07C317/34C07C211/26A61K31/12A61K31/4045C07C211/29C07C229/38C07C317/34BR19989805381A61K31/12A61K31/4045C07C211/26C07C211/29C07C229/38C07C317/34C07C211/26A61K31/12A61K31/4045C07C211/29C07C229/38C07C317/3