Spelling suggestions: "subject:"cyclosporine A""
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Effects of Cyclosporin A on Peripheral Immune ToleranceVanier, Laurent E. January 1994 (has links)
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A study of the medicinal chemistry related to the C9-ene amino acid of cyclosporinChan, Weng C. January 1988 (has links)
No description available.
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Analysis of Interieukin-8 Gene Promoter function in Human Osteoblast-like Cells : Regulation by Ca^<2+>-signaling and Cyclosporin AMITSUYAMA, Hirohito, KAMBE, Fukushi, MURAKAMI, Ryuichiro, ISHIGURO, Naoki, SEO, Hisao 12 1900 (has links)
国立情報学研究所で電子化したコンテンツを使用している。
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Daunorubicin Kinetics and Drug Resistance in LeukaemiaJanuary 1996 (has links)
The aims of this thesis were to examine: (1) plasma and cellular pharmacokinetics of daunorubicin and its major metabolite daunorubicinol in patients with acute leukaemia, and the relationships between pharmacokinetics, patient response and the presence of P glycoprotein; (2) actions of the multidrug resistance reversing agents cyclosporin A and trifluoperazine, at clinically achievable concentrations, on daunorubicin accumulation and retention in human leukaemia cell lines and patients with acute leukaemia; and (3) effect of daunorubicin on the cell membrane of both sensitive and resistant cell lines, with and without the multidrug resistance reversing agents. Twenty-seven patients with acute leukaemia received daunorubicin as part of induction therapy. The plasma and cellular levels of daunorubicin and its metabolite daunorubicinol were determined using HPLC. There were no significant differences between patients who went into complete remission (12 out of 23) compared to those who did not respond for any of the plasma pharmacokinetic parameters. There was a significant difference in the cellular daunorubicin and daunorubicinol area under the concentration-time curve between responders and non responders (p less than 0.02), as well as in cellular Cmax, cellular clearance and cellular volume of distribution. Eleven patients were P glycoprotein positive and 10 P glycoprotein negative (no sample available for 2 patients). There was no correlation between patient response and the presence of P glycoprotein; nor a correlation between the cellular concentration of daunorubicin or daunorubicinol and P glycoprotein. Patients responding to chemotherapy had higher cellular daunorubicin and daunorubicinol compared to non responders. In contrast to in vitro studies, overexpression of P glycoprotein was not the reason for the lower cellular daunorubicin levels. Cyclosporin A was capable of increasing both cellular accumulation and retention in the drug resistant CEM/VLB and HL 60/ADR cell lines, but not in the drug sensitive CEM and HL 60 cell lines. Trifluoperazine had no effect in any of the four cell lines. In contrast to the cell line findings, only the combination of cyclosporin A and trifluoperazine were able to increase both accumulation and retention in the blast cells of patients at initial presentation. The multidrug resistant reversing agents alone had no effect in increasing accumulation or retention in the blast cells of P glycoprotein positive patients, nor patients in relapse. The cell line studies show that at clinically relevant concentrations only cyclosporin A is capable of increasing daunorubicin accumulation in both the drug resistant P glycoprotein positive (VLB) and P glycoprotein negative (ADR) cell lines. Thus, cyclosporin A does not work only by inhibiting the actions of P glycoprotein. Trifluoperazine was unable to reverse drug resistance at clinically relevant concentrations in either cell lines or patient blast cells. However, the combination of cyclosporin A and trifluoperazine increased accumulation in patient blast cells at initial presentation, suggesting that these agents may be more useful in patients at initial presentation than relapse. Daunorubicin was immobilised by linking it to poly vinyl alcohol and the effect of immobilised-daunorubicin was studied on the four cell lines above. The immobilised-daunorubicin was able to decrease cell growth in the drug sensitive HL 60 cell line but not in the drug resistant VLB or ADR cell lines. Poly vinyl alcohol itself was cytotoxic to the CEM cell line. The multidrug resistance reversing agents cyclosporin A and trifluoperazine were only capable of increasing cytotoxicity in the HL 60 cell line, with no effect in the drug resistant VLB or ADR cell lines.
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Canine Pancreatic Allotransplantation with Duodenum (Pancreaticoduodenal Transplantation) Using Cyclosporin AKONDO, TATSUHEI, TAKAGI, HIROSHI, MORIMOTO, TAKESHI 01 1900 (has links)
No description available.
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Daunorubicin Kinetics and Drug Resistance in LeukaemiaJanuary 1996 (has links)
The aims of this thesis were to examine: (1) plasma and cellular pharmacokinetics of daunorubicin and its major metabolite daunorubicinol in patients with acute leukaemia, and the relationships between pharmacokinetics, patient response and the presence of P glycoprotein; (2) actions of the multidrug resistance reversing agents cyclosporin A and trifluoperazine, at clinically achievable concentrations, on daunorubicin accumulation and retention in human leukaemia cell lines and patients with acute leukaemia; and (3) effect of daunorubicin on the cell membrane of both sensitive and resistant cell lines, with and without the multidrug resistance reversing agents. Twenty-seven patients with acute leukaemia received daunorubicin as part of induction therapy. The plasma and cellular levels of daunorubicin and its metabolite daunorubicinol were determined using HPLC. There were no significant differences between patients who went into complete remission (12 out of 23) compared to those who did not respond for any of the plasma pharmacokinetic parameters. There was a significant difference in the cellular daunorubicin and daunorubicinol area under the concentration-time curve between responders and non responders (p less than 0.02), as well as in cellular Cmax, cellular clearance and cellular volume of distribution. Eleven patients were P glycoprotein positive and 10 P glycoprotein negative (no sample available for 2 patients). There was no correlation between patient response and the presence of P glycoprotein; nor a correlation between the cellular concentration of daunorubicin or daunorubicinol and P glycoprotein. Patients responding to chemotherapy had higher cellular daunorubicin and daunorubicinol compared to non responders. In contrast to in vitro studies, overexpression of P glycoprotein was not the reason for the lower cellular daunorubicin levels. Cyclosporin A was capable of increasing both cellular accumulation and retention in the drug resistant CEM/VLB and HL 60/ADR cell lines, but not in the drug sensitive CEM and HL 60 cell lines. Trifluoperazine had no effect in any of the four cell lines. In contrast to the cell line findings, only the combination of cyclosporin A and trifluoperazine were able to increase both accumulation and retention in the blast cells of patients at initial presentation. The multidrug resistant reversing agents alone had no effect in increasing accumulation or retention in the blast cells of P glycoprotein positive patients, nor patients in relapse. The cell line studies show that at clinically relevant concentrations only cyclosporin A is capable of increasing daunorubicin accumulation in both the drug resistant P glycoprotein positive (VLB) and P glycoprotein negative (ADR) cell lines. Thus, cyclosporin A does not work only by inhibiting the actions of P glycoprotein. Trifluoperazine was unable to reverse drug resistance at clinically relevant concentrations in either cell lines or patient blast cells. However, the combination of cyclosporin A and trifluoperazine increased accumulation in patient blast cells at initial presentation, suggesting that these agents may be more useful in patients at initial presentation than relapse. Daunorubicin was immobilised by linking it to poly vinyl alcohol and the effect of immobilised-daunorubicin was studied on the four cell lines above. The immobilised-daunorubicin was able to decrease cell growth in the drug sensitive HL 60 cell line but not in the drug resistant VLB or ADR cell lines. Poly vinyl alcohol itself was cytotoxic to the CEM cell line. The multidrug resistance reversing agents cyclosporin A and trifluoperazine were only capable of increasing cytotoxicity in the HL 60 cell line, with no effect in the drug resistant VLB or ADR cell lines.
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Modulatoren des Calcineurin-NFATc-Signalweges in humanen TH-Zellen / Modulators of the calcineurin-NFATc signalling pathway in human T helper cellsSieber, Matthias January 2010 (has links)
Die Ca2+/Calmodulin-aktivierte Serin/Threonin-Phosphatase Calcineurin ist ein Schlüsselmolekül des T-Zell-Rezeptorabhängigen Signalnetzwerkes. Calcineurin aktiviert die Transkriptionsfaktoren der NFATc-Familie durch Dephosphorylierung und reguliert darüber die Expression wichtiger Zytokine und Oberflächenproteine. Die Aktivität von Calcineurin wird durch zahlreiche endogene Proteine moduliert und ist Angriffspunkt der immunsuppressiven Substanzen Cyclosporin A und FK506.
In dieser Arbeit wurde der alternative niedermolekulare Calcineurin-NFATc-Inhibitor NCI3 hinsichtlich seiner Effekte auf T-Zell-Rezeptor-abhängige Signalwege charakterisiert. Die Ergebnisse zeigen, daß das Pyrazolopyrimidinderivat NCI3 nichttoxisch und zellmembranpermeabel ist. In T-Zell-Rezeptor-stimulierten primären humanen TH-Zellen unterdrückt NCI3 die Proliferation und IL-2-Produktion (IC50-Wert ~4 µM), da die Dephosphorylierung von NFATc und die anschließende nukleäre Translokation gehemmt wird. NCI3 inhibiert die calcineurinabhängige NFAT- und NF-κB-, aber nicht die AP-1-kontrollierte Reprtergenexpression, in mikromolaren Konzentrationen (IC50-Werte 2 bzw. 7 µM). Im Gegensatz zu Cyclosporin A stört NCI3 nicht die Phosphataseaktivität von Calcineurin, sondern interferiert mit der Calcineurin-NFATc-Bindung.
Ein wichtiges endogenes Modulatorprotein für die Calcineurinaktivität ist RCAN1, das vermutlich den Calcineurin-NFATc-Signalweg über einen negativen Rückkopplungsmechanismus reguliert.
Hier wurde gezeigt, daß RCAN1 in humanen TH-Zellen exprimiert wird. Die Spleißvariante RCAN1-1 ist in ruhenden T-Zellen basal exprimiert und wird nicht durch T-Zell-Rezeptor-Stimulierung in seiner Expression verändert. RCAN1-4 dagegen ist in ruhenden Zellen kaum zu detektieren und wird stimulierungsabhängig induziert. Durch die Verwendung Calcineurin-NFATc-spezifischer Inhibitoren wie NCI3 wurde gezeigt, daß die RCAN1-4-Induktion durch diesen Signalweg limitiert ist.
Die in dieser Arbeit gewonnenen Daten und Erkenntnisse tragen dazu bei, das Verständnis der Funktion und Regulation von Calcineurin in T-Zellen zu vertiefen. / The Ca2+/calmodulin dependent serine/threonine phosphatase calcineurin is a key molecule in the T cell receptor dependent signalling network. Calcineurin dephosphorylates and thereby activates the transcription factors of the NFATc family that, among others, control the expression of important cytokines and cell surface molecules. The activity of Calcineurin is modulated by several endogenous proteins and is inhibited by the immunosuppressants cyclosporine A and FK506.
Here, the novel low molecular weight inhibitor NCI3 was characterized in respect to its effects on T cell receptor dependent signalling. The results of this work show, that the pyrazolopyrimidine derivate NCI3 is nontoxic and permeates the cell membrane. Upon TCR stimulation NCI3 suppresses T cell proliferation and IL-2 production of primary human TH cells with IC50 values of ~4 µM by blocking the dephosphorylation and subsequent nuclear translocation of NFATc. NCI3 conse-quently inhibits calcineurin dependent NFAT- and NF-κB-, but not AP-1-controlled reporter gene expression, in micromolar concentrations (IC50 values 2 and 7 µM, respectively). In opposite to cyclosporine A and FK506, NCI3 does not interfere with the phosphatase activity of calcineurin but rather disturbs the calcineurin-NFATc interaction.
A major endogenous modulator of calcineurin is the protein RCAN1, which is supposed to regulate calcineurin-NFATc signalling in a negative feedback loop.
The presented data show that RCAN1 is expressed in human TH cells. The splice variant RCAN1-1 is basally expressed in resting T cells, and its expression levels are not changed by T cell receptor stimulation. Expression of RCAN1-4, on the other hand, is nearly undetectable in resting TH cells and is induced upon cell stimulation. By using calcineurin-NFATc specific inhibitors such as NCI3 it could be shown that RCAN1-4 induction is limited by this pathway.
This work provides a comprehensive characterization of the novel inhibitor NCI3 and insights into the regulation of calcineurin by RCAN1 in human TH cells.
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Associação entre crescimento gengival e a condição clínica e microbiológica periodontal de pacientes transplantados cardíacos submetidos à terapia com ciclosporina-A. Estudo transversal. / Association between gingival overgrowth and clinical and microbiological periodontal conditions in heart transplant patients under cyclosporin-a therapy. A cross-sectional study.Giuseppe Alexandre Romito 22 September 2000 (has links)
Foram examinados 30 pacientes (10 mulheres e 20 homens - média 44,89 anos). Todos os pacientes estavam sob terapia com ciclosporina-A (CsA), e não tinham sido submetidos à antibioticoterapia e nem a tratamento periodontal prévio, por pelo menos 3 meses do início do estudo. O paciente deveria ter, no mínimo 6 dentes. Foram registrados os índices de placa bacteriana (IP), índice gengival (IG), e os valores de profundidade clínica de sondagem (PCS) e nível clínico de inserção (NCI). Análise microbiológica foi realizada a partir de amostras coletadas do sulco/bolsa (s/b) gengival e da saliva estimulada (se). Os pacientes foram divididos em 2 grupos: com crescimento gengival (CCG) e sem crescimento gengival (SCG). Após análise estatística (Teste do Qui-quadrado; teste t de Student; Prova exata de Fisher; ?£0,05), concluiu-se que não houve diferença entre os dois grupos de pacientes com relação ao sexo dos pacientes, dosagem de CsA, tempo decorrido após o transplante, IP, IG, PCS e NCI. O exame microbiológico das amostras coletadas mostrou a presença de Actinobacillus actinomycetemcomitans (s/b-23% e se-13%), Porphyromonas sp. (s/b-36% e se-13%), Prevotella sp. (s/b-93% e se-93%), Campylobacter sp. (s/b-30%), Fusobacterium sp. (s/b-66% e se-50%), Peptostreptococcus micros (66%) e Streptococcus b-hemolítico (s/b-57% e se-83%). Destes microorganismos, apenas P. micros mostrou-se diretamente associado ao grupo CCG. Foi possível a detecção de Candida sp. (s/b-30% e se-30%), na amostra de saliva estimulada a presença de Candida sp. estava associada aos pacientes SCG. / This cross-sectional study was aimed at determining the association among cyclosporin-A induced gingival overgrowth in heart transplant patients and periodontal and microbiological conditions. Thirty patients (10 female, 20 male) undergoing cyclosporin treatment were evaluated using gingival index (GI), plaque index (PI), pocket depth (PD) and clinical attachment level (CAL). Subgingival and saliva samples were collected for microbial analysis. All patients had 6 teeth at least. Exclusion criteria was no antibiotic and/or periodontal treatment could been done 3 months prior. Patients were divided in two groups: with gingival overgrowth (WGO) and no gingival overgrowth (NGO). After statistical analysis (Qui-square test, t-Student test, Exact Fisher test, ?£0,05), was concluded that there was no statistically differences between WGO and NGO groups when compared CsA dosage, time of transplant, GI, PI, PD and CAL. Microbiological exam from subgingival sample detected: A. actinomycetemcomitans (23%), Porphyromonas p. (36%), Prevotella sp. (93%), Campylobacter sp. (30%), Fusobacterium sp. (66%), Peptostreptococcus micros (66%), Streptococcus b-hemolítico (57%). It was found a positive association between P. micros and WGO group. From subgingival and saliva samples was possible the detection of microorganism Candida sp. (30%). There was a positive association between presence of Candida sp. in saliva and NGO group.
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Associação entre crescimento gengival e a condição clínica e microbiológica periodontal de pacientes transplantados cardíacos submetidos à terapia com ciclosporina-A. Estudo transversal. / Association between gingival overgrowth and clinical and microbiological periodontal conditions in heart transplant patients under cyclosporin-a therapy. A cross-sectional study.Romito, Giuseppe Alexandre 22 September 2000 (has links)
Foram examinados 30 pacientes (10 mulheres e 20 homens - média 44,89 anos). Todos os pacientes estavam sob terapia com ciclosporina-A (CsA), e não tinham sido submetidos à antibioticoterapia e nem a tratamento periodontal prévio, por pelo menos 3 meses do início do estudo. O paciente deveria ter, no mínimo 6 dentes. Foram registrados os índices de placa bacteriana (IP), índice gengival (IG), e os valores de profundidade clínica de sondagem (PCS) e nível clínico de inserção (NCI). Análise microbiológica foi realizada a partir de amostras coletadas do sulco/bolsa (s/b) gengival e da saliva estimulada (se). Os pacientes foram divididos em 2 grupos: com crescimento gengival (CCG) e sem crescimento gengival (SCG). Após análise estatística (Teste do Qui-quadrado; teste t de Student; Prova exata de Fisher; ?£0,05), concluiu-se que não houve diferença entre os dois grupos de pacientes com relação ao sexo dos pacientes, dosagem de CsA, tempo decorrido após o transplante, IP, IG, PCS e NCI. O exame microbiológico das amostras coletadas mostrou a presença de Actinobacillus actinomycetemcomitans (s/b-23% e se-13%), Porphyromonas sp. (s/b-36% e se-13%), Prevotella sp. (s/b-93% e se-93%), Campylobacter sp. (s/b-30%), Fusobacterium sp. (s/b-66% e se-50%), Peptostreptococcus micros (66%) e Streptococcus b-hemolítico (s/b-57% e se-83%). Destes microorganismos, apenas P. micros mostrou-se diretamente associado ao grupo CCG. Foi possível a detecção de Candida sp. (s/b-30% e se-30%), na amostra de saliva estimulada a presença de Candida sp. estava associada aos pacientes SCG. / This cross-sectional study was aimed at determining the association among cyclosporin-A induced gingival overgrowth in heart transplant patients and periodontal and microbiological conditions. Thirty patients (10 female, 20 male) undergoing cyclosporin treatment were evaluated using gingival index (GI), plaque index (PI), pocket depth (PD) and clinical attachment level (CAL). Subgingival and saliva samples were collected for microbial analysis. All patients had 6 teeth at least. Exclusion criteria was no antibiotic and/or periodontal treatment could been done 3 months prior. Patients were divided in two groups: with gingival overgrowth (WGO) and no gingival overgrowth (NGO). After statistical analysis (Qui-square test, t-Student test, Exact Fisher test, ?£0,05), was concluded that there was no statistically differences between WGO and NGO groups when compared CsA dosage, time of transplant, GI, PI, PD and CAL. Microbiological exam from subgingival sample detected: A. actinomycetemcomitans (23%), Porphyromonas p. (36%), Prevotella sp. (93%), Campylobacter sp. (30%), Fusobacterium sp. (66%), Peptostreptococcus micros (66%), Streptococcus b-hemolítico (57%). It was found a positive association between P. micros and WGO group. From subgingival and saliva samples was possible the detection of microorganism Candida sp. (30%). There was a positive association between presence of Candida sp. in saliva and NGO group.
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Avaliação do efeito da Sinvastatina em ratos submetidos a periodontite experimental e imunossuprimidos por Ciclosporina-A e TacrolimusNassar, Patrícia Oehlmeyer [UNESP] 27 March 2008 (has links) (PDF)
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nassar_po_dr_arafo.pdf: 667309 bytes, checksum: 5cca54174057241803a84367b451b25b (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Há relatos na literatura que os ossos de maneira geral assim como o processo alveolar são acometidos pela Ciclosporina-A (CsA) desequilibrando sua homeostase, induzindo a perda óssea. Alguns trabalhos experimentais mostram que o Tacrolimus (FK506) induz perda óssea, enquanto outros relatam conferir uma proteção contra inflamação e perda óssea associada à periodontite, em ratos com doença periodontal induzida. Adicionalmente, tem sido recentemente revelado que algumas estatinas poderiam estimular a formação óssea e inibir a reabsorção óssea. Assim os objetivos do estudo foram avaliar os efeitos da administração da CsA, FK506 associados ou não com sinvastatina no desenvolvimento da doença periodontal induzida em ratos submetidos a modelo de periodontite experimental, através de avaliações bioquímica, molecular e esterométrica. Foram utilizados 320 ratos divididos em 32 grupos e em diferentes períodos de 15, 30 e 60 dias associados ou não a periodontite experimental e/ou a administração diária de CsA (10mg/kg por peso corporal), FK506 (1mg/kg por peso corporal ) e Sinvastatina (20mg/kg por peso corporal). Ao final de cada período experimental, coletas de sangue foram realizadas para medir os níveis séricos de cálcio, fósforo e fosfatase alcalina e biópsias gengivais para as avaliações de ELISA e PCR. Após o processamento histológico, a densidade volumétrica de osso, osteoblastos e osteoclastos foram medidas na região de primeiro molar inferior. Após 15 e 30 dias de tratamento quando associado ao uso de Sinvastatina, houve melhora nos parâmetros bioquímicos em relação à CsA (p<0.05) e sem ser significante em relação ao FK506 (p>0.05) com ou sem associação de doença periodontal. / In the literature that the bones as well as the alveolar process are attack by the CsA having unbalanced its homeostasis, inducing the bone loss. Some experimental studies show that the FK506 induced bone loss, while others demonstrated to confer a protection against inflammation and bone loss associate to the periodontitis, in rats with induced periodontal disease. Additionally, he has been recently disclosed that some statins could stimulate the bone formation and inhibit the bone resorption. Thus the objectives of the study had been to evaluate the effect of the administration of the CsA, FK506 associates or not with sinvastatin in the development of the induced periodontal disease in submitted rats the model of experimental periodontite, through evaluations biochemistry, molecular and stereometric. 320 rats divided in 32 groups and different periods of 15, 30 and 60 days had been used associates or not to the experimental periodontitis and/or the daily administration of CsA (10mg/kg body weight), FK506 (1mg/kg body weight) and Sinvastatin (20mg/kg body weight). At the end of period experimental, blood collection was obtained and serum levels calcium, phosphorus and alkaline phosphatase were measured and ELISA end PCR analysis were extracted from gingival tissue samples. After the histologic processing, the volumetric density of bone, osteoblasts and osteoclasts had been measured in the first region molar inferior. After 15 and 30 days of treatment when associated to the use of sinvastatin, it had improvement in the parameters biochemistries in relation to the CsA (p<0,05) with or without association of periodontal disease The same characteristics had been presented in the stereometric analysis.
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