Pharmacokinetic/pharmacodynamic relationships of FTY720 in kidney transplant recipients

FTY720 is a new and effective immunosuppressive agent, which produces peripheral blood lymphopenia through a lymphocyte homing effect. We investigated the relationship between the dose of FTY720 or blood concentration (pharmacokinetics, PK) and peripheral lymphopenia (pharmacodynamics, PD) in 23 kidney transplant recipients randomized to receive FTY720 (0.25-2.5 mg/day) or mofetil mycophenolate (2 mg/day) in combination with cyclosporine and steroids. FTY720 dose, blood concentrations and lymphocyte counts were determined weekly before and 4 to 12 weeks after transplantation. The effect of PD was calculated as the absolute lymphocyte count or its reductions. PK/PD modeling was used to find the best-fit model. Mean FTY720 concentrations were 0.36 ± 0.05 (0.25 mg), 0.73 ± 0.12 (0.5 mg), 3.26 ± 0.51 (1 mg), and 7.15 ± 1.41 ng/ml (2.5 mg) between 4 and 12 weeks after transplantation. FTY720 PK was linear with dose (r² = 0.98) and showed low inter- and intra-individual variability. FTY720 produced a dose-dependent increase in mean percent reduction of peripheral lymphocyte counts (38 vs 42 vs 56 vs 77, P < 0.01, respectively). The simple Emax model [E = (Emax * C)/(C + EC50)] was the best-fit PK/PD modeling for FTY720 dose (Emax = 87.8 ± 5.3% and ED50 = 0.48 ± 0.08 mg, r² = 0.94) or concentration (Emax = 78.3 ± 2.9% and EC50 = 0.59 ± 0.09 ng/ml, r² = 0.89) vs effect (% reduction in peripheral lymphocytes). FTY720 PK/PD is dose dependent and follows an Emax model (EC50 = 0.5 mg or 0.6 ng/ml). Using lymphopenia as an FTY720 PD surrogate marker, high % reductions (~80%) in peripheral lymphocytes are required to achieve best efficacy to prevent acute allograft rejection.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Hospital do Rim e HipertensãoNovartis PharmaceuticalsUNIFESP, EPM, Hospital do Rim e HipertensãoSciEL

Exploratory calcineurin inhibitor-free regimens in living-related kidney transplant recipients

Chronic allograft nephropathy is among the major causes of graft loss even in low-risk kidney transplant recipients and correlates with acute nephrotoxic events during the first year post-transplant. Therefore, calcineurin inhibitor-free regimens may improve patient and graft survival among recipients of living-related kidney transplants. To confirm this hypothesis, we evaluated the efficacy and safety of two calcineurin inhibitor-free regimens in 92 low-risk recipients of one-haplotype living-related kidney transplants. Immunosuppression consisted of tacrolimus, azathioprine and prednisone (group I, GI, N = 38), 2 doses of daclizumab, mycophenolate mofetil (MMF), and prednisone (GII, N = 33) and 2 doses of daclizumab, MMF, sirolimus and prednisone (GIII, N = 21). At 12 months, treatment failure (biopsy-confirmed acute rejection, graft loss or death) was higher in GII compared to GIII and GI (54.5 vs 24.0 vs 13.1%, P < 0.01, respectively). In patients of black ethnicity the incidence of acute rejection was 25 vs 83.3 vs 20% (P = 0.055), respectively. Patient and graft survival was comparable. There were no differences in mean creatinine or calculated creatinine clearance at 12 months. Overall incidence of post-transplant diabetes mellitus (3.3%) and cytomegalovirus disease (4.3%) was similar in all groups. Further development of effective calcineurin inhibitor-free regimens should exclude patients of black ethnicity and may need full-induction therapy, perhaps with depleting agents, and concentration-controlled use of sirolimus and MMF.Universidade Federal de São Paulo (UNIFESP) Hospital do Rim e Hipertensão Divisão de NefrologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de PatologiaUNIFESP, Hospital do Rim e Hipertensão Divisão de NefrologiaUNIFESP, Depto. de PatologiaSciEL

GEOTECHNOLOGY AND MULTIVARIATE ANALYSIS TO INVESTIGATION OF THE TYPOLOGY OF THE AGRICULTURAL USE OF THE STATE OF MATO GROSSO

Objetivou-se identificar o padrão de distribuição espacial dos principais tipos agropecuários do estado de Mato Grosso, visando a caracterização e agrupamento das municipalidades mato-grossense segundo o seu grau de similaridade em relação as formas de uso da terra. O estudo abrangeu os 141 municípios do estado de Mato Grosso, cujos dados para elaboração do trabalho foram provenientes do Censo Agropecuário de 2006, estes foram sistematizados em duas matrizes. Aplicou-se o método de análise de agrupamento realizado por meio da extensão “Action Stat”, no software livre “Excel”. Para a identificação do padrão das formas de uso agropecuário os resultados foram representados adotando-se as técnicas da cartografia temática. Das 12 regiões de planejamento, a região Sudeste de planejamento (V) é a que apresenta maior diversificação produtiva. Sabe-se que o dinamismo de produção é de suma importância para a economia regional, não apenas concentrando sua renda em uma única produção. As regiões de planejamento I e XI predominam vegetação, cujas atividades de uso da terra, tanto agrícola quanto pecuária são incipientes. Em Mato Grosso predomina o tipo de uso da terra voltada para exploração de pastagens, visando o desenvolvimento da bovinocultura. A produção agrícola do Estado apresenta-se centralizada em 11 municípios

EFFECT OF ECTOMYCORRHIZAL FUNGI ISOLATES INOCULATION IN Eucalyptus grandis Hill ex Maiden SEEDLINGS DEVELOPMENT

No Estado do Rio Grande do Sul, os reflorestamentos de eucalipto t\ueam se concentrado em solos com baixa fertilidade natural, e o desempenho dessas mudas poder\ue1 depender da forma\ue7\ue3o da associa\ue7\ue3o ectomicorr\uedzica. Nesse trabalho, avaliou-se o efeito da inocula\ue7\ue3o dos isolados de fungos ectomicorr\uedzicos UFSC-Pt116, UFSC-Pt188 e UFSC-SA9, individualmente e em mistura, sobre mudas de Eucalyptus grandis . As avalia\ue7\uf5es foram realizadas aos 30, 45, 60, 75 e 90 dias ap\uf3s semeadura. A inocula\ue7\ue3o individual do isolado f\ufangico ectomicorr\uedzico UFSC-Pt116 promoveu maior altura e massa seca da parte a\ue9rea. As mudas inoculadas com mistura dos isolados f\ufang\uedcos UFSC-Pt116 + UFSC-Pt188 + UFSC-SA9 acumularam maior quantidade de f\uf3sforo aos 90 dias. Para os teores de nitrog\ueanio e pot\ue1ssio, e massa seca de ra\uedzes n\ue3o mostrou diferen\ue7a significativa entre os tratamentos.In the Rio Grande do Sul state, where eucalyptus reforestation is common in low fertility soils, the seedling performance may depend on the ectomycorrhizal association. In this paper, the inoculation effects of UFSC-Pt116, UFSC-Pt188 and UFSC-SA9 ectomycorrhizal fungi isolates, individually and in mixture, on Eucalyptus grandis seedlings were evaluated. Evaluations were performed at 30, 45, 60, 75, and 90 days after sowing. The individual inoculation of UFSC-Pt116 isolate promoted highest height and aerial dry mass. The seedlings inoculated with the mixture UFSC-Pt116 + UFSC-Pt188 + UFSC-SA9 accumulated highest amounts of phosphorus at 90 days. The nitrogen and potassium concentrations, and root dry mass did not show significant differences among the treatments

ECTOMYCORRHIZAL ISOLATES IN THE SEEDLING PRODUCTION OF Eucalyptus grandis W. Hill ex. Maiden IN QUARTZARENIC NEOSOLS

No estado do Rio Grande do Sul, os reflorestamentos de eucalipto encontram-se, geralmente, em solos de baixa fertilidade natural, favorecendo a associa\ue7\ue3o ectomicorr\uedzica. Neste trabalho, avaliou-se o efeito da inocula\ue7\ue3o dos isolados de fungos ectomicorr\uedzicos UFSC-Pt116, UFSC-Pt188 e UFSC-SA9, sobre plantas de Eucalyptus grandis, em Neossolo Quartzar\ueanico. As avalia\ue7\uf5es foram realizadas aos 30, 45, 60, 75 e 90 dias ap\uf3s semeadura. Plantas inoculadas com os isolados UFSC-Pt116, UFSC-Pt188 e UFSC-SA9 alcan\ue7aram maior altura, di\ue2metro do caule, massa seca da parte a\ue9rea e volume de ra\uedzes em rela\ue7\ue3o ao controle. Plantas inoculadas com o isolado de fungo ectomicorr\uedzico UFSC-Pt188 apresentaram maior teor de f\uf3sforo e pot\ue1ssio na parte a\ue9rea que as plantas n\ue3o inoculadas. A inocula\ue7\ue3o com o isolado f\ufangico ectomicorr\uedzico UFSC-Pt116 promoveu maior altura e massa seca da parte a\ue9rea. Para os teores de nitrog\ueanio e pot\ue1ssio, e para massa seca de ra\uedzes n\ue3o foram observadas diferen\ue7as significativas entre os tratamentos. A inocula\ue7\ue3o com os fungos ectomicorr\uedzicos UFSC-Pt116, UFSC-SA9 e UFSC-Pt188 isoladamente, promoveram maior altura, di\ue2metro de caule, ac\ufamulo de massa seca da parte a\ue9rea e volume de ra\uedzes das plantas de Eucalyptus grandis.In Rio Grande do Sul state, the eucalyptus planted forests are cultivated in low fertility soils, which contribute to ectomycorrhizal association. This study evaluated the effect of ectomycorrhizal isolates UFSC-Pt116, UFSC-Pt188 and UFSC-SA9 inoculation, individually and in combination, with Eucalyptus grandis in Quartzarenic Neosols. Evaluations were performed at 30, 45, 60, 75 and 90 days after sowing. Plants inoculated with isolates UFSC-Pt116, UFSC-Pt188 and UFSC-SA9 showed highest height, stem diameter, dry mass of shoot and root volume than the control. Plants inoculated with the ectomycorrhizal fungus isolate UFSC-Pt188 showed highest content of phosphorus and potassium in shoots than non-inoculated plants. Inoculation individual ectomycorrhizal isolate UFSC-Pt116 promoted the highest height and shoot dry mass. For nitrogen and potassium, and root biomass have not showed significant differences between treatments. Then inoculation with ectomycorrhizal UFSC-Pt116, UFSC-Pt188 and UFSC-SA9 alone promoted highest height, stem diameter, dry mass of shoot and plant root volume of Eucalyptus grandis

Substract and phosphour influence in seedling production of Acacia mearnsii De Wild level

A inocula\ue7\ue3o de fungos micorr\uedzicos arbusculares (FMAs) \ue9 vi\ue1vel em mudas de esp\ue9cies florestais. O objetivo deste trabalho foi avaliar o estabelecimento de duas esp\ue9cies de FMAs na produ\ue7\ue3o de mudas de Acacia mearnsii em diferentes substratos e doses de f\uf3sforo. O experimento constou de cinco tratamentos, sendo dois tratamentos de inocula\ue7\ue3o de esp\ue9cies de FMAs, ( Glomus clarum Nicolson &amp; Schenck e Glomus etunicatum Becker &amp; Gerdemann) e tr\ueas tratamentos com diferentes substratos (mecplani, turfa f\ue9rtil e Neossolo Quartzar\ueanico); com cinco doses de f\uf3sforo (0, 50, 100, 500 e 1000 mg.kg-1), e dez repeti\ue7\uf5es. Alto n\uedvel de P no substrato n\ue3o impediu coloniza\ue7\ue3o micorr\uedzica das ra\uedzes. Os isolados G. clarum e G. etunicatum apresentaram alta efici\ueancia na coloniza\ue7\ue3o das ra\uedzes da A. mearnsii, e os substratos mecplani e turfa-f\ue9rtil foram os mais eficientes na produ\ue7\ue3o das mudas.The inoculation of mycorrhizal arbuscular fungi (FMAs) is viable in forest species. The aim of this study was to evaluate the establishment of two species of FMAs, in Ac\ue1cia mearnsii production, considering different substracts and phosphour levels. The experiment was carried out with five treatments, with two species of FMAs ( Glomus clarum Nicolson &amp; Schenck and Glomus etunicatum Becker &amp; Gerdemann), and three kinds of substracts (Mecplani, Fertil Turfa and Neossolo Quartzar\ueanico) with four phosphour levels, with 10 repetitions. The high level of P in the substract did not influence the mycorrhizal colonization in the roots. These mycorrhizal fungi showed high efficiency in roots colonization of A. mearnsii. The Mecplani and Fertil Turfa substracts were the most efficient ones in seedling growing