Acidez potencial estimada pelo método do pH SMP em solos da região do Vale do Jequitinhonha no Estado de Minas Gerais

A acidez potencial tem grande importância pelo seu uso na determinação da necessidade de calagem pelo método da saturação de bases. O objetivo deste trabalho foi definir uma equação de regressão que estime o teor de H + Al a partir do pH SMP medido na suspensão solo-solução SMP, associada à determinção do pH em água, para solos da Região do Vale do Jequitinhonha. As análises dos teores de H + Al, extraídos por acetato de cálcio 0,5 mol L-1 a pH 7,0, e dos valores de pH SMP foram realizadas no laboratório de fertilidade do solo da UFVJM em 50 amostras de solos, com valores de pH em água variando de 4,0 a 7,6, teores de carbono orgânico de 1 a 29 g kg-1 e os de argila de 100 a 810 g kg-1. A acidez potencial, expressa em cmol c dm-3, pode ser estimada pelo uso do pH SMP, por meio da equação: Ln (H + Al) = 8,26 - 1,124312 pH SMP (R² = 0,97).

Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial.

PURPOSE: This study assessed whether a cycle of "routine" therapeutic drug monitoring (TDM) for imatinib dosage individualization, targeting an imatinib trough plasma concentration (C min) of 1,000 ng/ml (tolerance: 750-1,500 ng/ml), could improve clinical outcomes in chronic myelogenous leukemia (CML) patients, compared with TDM use only in case of problems ("rescue" TDM). METHODS: Imatinib concentration monitoring evaluation was a multicenter randomized controlled trial including adult patients in chronic or accelerated phase CML receiving imatinib since less than 5 years. Patients were allocated 1:1 to "routine TDM" or "rescue TDM." The primary endpoint was a combined outcome (failure- and toxicity-free survival with continuation on imatinib) over 1-year follow-up, analyzed in intention-to-treat (ISRCTN31181395). RESULTS: Among 56 patients (55 evaluable), 14/27 (52 %) receiving "routine TDM" remained event-free versus 16/28 (57 %) "rescue TDM" controls (P = 0.69). In the "routine TDM" arm, dosage recommendations were correctly adopted in 14 patients (median C min: 895 ng/ml), who had fewer unfavorable events (28 %) than the 13 not receiving the advised dosage (77 %; P = 0.03; median C min: 648 ng/ml). CONCLUSIONS: This first target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" because of small patient number and surprisingly limited prescriber's adherence to dosage recommendations. Favorable outcomes were, however, found in patients actually elected for target dosing. This study thus shows first prospective indication for TDM being a useful tool to guide drug dosage and shift decisions. The study design and analysis provide an interesting paradigm for future randomized TDM trials on targeted anticancer agents.

Estoques de carbono orgânico e de nitrogênio, pH e densidade de um Latossolo após três aplicações de lodos de esgoto

O elevado conteúdo de matéria orgânica de lodo de esgoto é uma das motivações para sua disposição no ambiente como condicionador do solo. O objetivo deste trabalho foi avaliar o efeito de aplicações consecutivas de lodo de esgoto sobre o acúmulo de C e de N (total e mineral), sobre o pH e sobre a densidade de um Latossolo. As avaliações foram feitas em duas profundidades do solo (0-0,1 e 0,2-0,4 m) após três cultivos de milho, em experimento realizado entre os anos de 1999 e 2001, em Jaguariúna-SP. Os tratamentos consistiram de cinco doses crescentes de dois tipos de lodo de esgoto, aplicadas a cada cultivo. O aumento das doses aplicadas (totalizando 0, 10.284, 20.568, 41.136 e 82.272 kg ha-1) do lodo da Estação de Tratamento de Esgotos de Franca-SP, de origem urbana, causou crescimento significativo dos estoques de C orgânico e de N na camada superficial. Nos tratamentos com o lodo da Estação de Tratamento de Esgotos de Barueri-SP (totalizando 0, 17.405, 34.810, 69.620 e 139.240 kg ha-1), produzido a partir de esgotos urbanos e industriais, apesar da incorporação de 14 % a mais de C ao solo, os estoques de C não foram influenciados pelas doses aplicadas e houve crescimento significativo dos estoques de N. A densidade na camada superficial diminuiu significativamente com o aumento das doses dos dois tipos de lodo de esgoto. Houve acidificação do solo nas duas camadas estudadas, com necessidade de duas calagens, após o segundo e terceiro cultivos. Observou-se lixiviação de N-mineral para maiores profundidades do solo.

Acumulação de silício em arroz em diferentes condições de pH da rizosfera

A quantidade de Si acumulada pelas plantas depende do teor de Si disponível, e este, do pH do solo. É possível que a absorção e acumulação de Si em gramíneas possam estar associadas ao pH rizosférico. Este trabalho teve como objetivo estudar o efeito do pH de rizosfera na disponibilidade do Si no solo, na acumulação por plantas de arroz de sequeiro (vr. Epagri 109) e na produção de massa seca. Para isso, instalou-se um ensaio em casa de vegetação, em parcela subdividida, no esquema fatorial 5 x 2. Os cinco tratamentos (TR) foram constituídos de dose única de N (200 mg kg-1), aplicada nas seguintes relações de N-NH4+e N-NO3-: TR1 = 0,0:1,0; TR2 = 0,25:0,75; TR3 = 0,50:0,50; TR4 = 0,75:0,25; e TR5 = 1,0:0,0. O fator subparcela consistiu da aplicação de 200 mg kg-1 de Si. As fontes de N usadas foram nitrato de cálcio e sulfato de amônio, e a fonte de Si foi o tetracloreto de Si, aplicadas em uma amostra de Neossolo Quartzarênico. Para inibir a nitrificação foram utilizados 10 mg kg-1 de nitrapirina nos tratamentos em que amônio foi empregado. Os valores de pH rizosférico decresceram proporcionalmente ao aumento da concentração de N-NH4+ e influenciaram de forma significativa o teor de Si no solo: quanto maior o pH rizosférico, maior a disponibilidade de Si e maior a absorção pela planta de arroz.

Adsorção de boro em solos ácricos em função da variação do pH

A adsorção de B pelo solo é o principal fenômeno que afeta sua disponibilidade e seu potencial de contaminação. Os objetivos deste estudo foram: (a) investigar os efeitos do pH na adsorção de B em amostras superficiais e subsuperficiais de um Latossolo Vermelho Acriférrico (LVwf) e de um Latossolo Amarelo Ácrico (LAw) - ambos com balanço positivo de cargas no horizonte Bw - e de um Nitossolo Vermelho eutroférrico (NVef); (b) avaliar a adequação do modelo de Langmuir em simular os resultados experimentais de adsorção; e (c) correlacionar os atributos químicos, físicos e mineralógicos dos solos com os valores de adsorção máxima (Ads máx) e do coeficiente de afinidade (K L), derivados das isotermas. Experimentos do tipo "batch" foram realizados para determinação da quantidade de boro adsorvido, tendo como eletrólito-suporte soluções de NaCl 0,01 mol L-1 com 0,1; 0,2; 0,4; 0,8; 1,2; 1,6; 2,0; e 4,0 µg mL-1 de B. Houve aumento da adsorção de B com a elevação do pH e da concentração inicial de B adicionado. Maiores quantidades de B foram adsorvidas na amostra superficial do NVef e nos horizontes Bw positivamente carregados dos Latossolos ácricos. A adsorção de B foi representada por isotermas dos tipos C (linear) e L (exponencial) e adequadamente ajustada pelo modelo de Langmuir. Os parâmetros Ads máx e K L estimados por regressão não-linear não se correlacionaram com o pH. No pH natural, teores de matéria orgânica (MO) e de argila foram as variáveis que mais influenciaram a Ads máx nas camadas superficiais. Nas camadas subsuperficiais, a Ads máx correlacionou-se negativamente com os teores de MO e positivamente com os de gibbsita. Teores de (hidr)óxidos de Fe cristalinos e amorfos estiveram correlacionados aos valores de K L obtidos nas amostras subsuperficiais e ao pH natural, bem como à Ads máx das camadas superficiais após aumento do pH.

Comparação de métodos para estimar a acidez potencial mediante determinação do pH SMP em Organossolos da Serra do Espinhaço Meridional

Apesar do potencial para uso agrícola e das características edáficas peculiares, poucos trabalhos são desenvolvidos para estimar a acidez potencial dos solos com elevado teor de matéria orgânica. O objetivo deste trabalho foi definir um modelo matemático que estime a acidez potencial (H + Al) a partir do pH SMP após determinação do pH do solo em água ou em solução de CaCl2 10 mmol L-1, com leitura do pH na suspensão ou sobrenadante da solução SMP de equilíbrio, em determinada relação solo:tampão SMP, em Organossolos da Serra do Espinhaço Meridional (SdEM), Estado de Minas Gerais, situada entre 17 ° 30 ' a 20 ° 30 ' S e 43 ° a 44 ° W. Foram utilizadas 22 amostras de Organossolos classificados como Organossolo Háplico sáprico térrico, Organossolo Háplico fíbrico típico e Organossolo Háplico hêmico típico da SdEM. A acidez potencial dos Organossolos da SdEM pode ser estimada satisfatoriamente por meio do pH SMP na relação solo:tampão SMP de 10:10 medido na suspensão solo-solução SMP associada à rotina de determinação do pH do solo em água. O C orgânico foi o atributo químico que mais influenciou a acidez potencial dos Organossolos da SdEM.

Protective effect of divalent cations against aluminum toxicity in soybean

A large proportion of soybean fields in Brazil are currently cultivated in the Cerrado region, where the area planted with this crop is growing considerably every year. Soybean cultivation in acid soils is also increasing worldwide. Since the levels of toxic aluminum (Al) in these acid soils is usually high it is important to understand how cations can reduce Al rhizotoxicity in soybean. In the present study we evaluated the ameliorative effect of nine divalent cations (Ca, Mg, Mn, Sr, Sn, Cu, Zn, Co and Ba) in solution culture on Al rhizotoxicity in soybean. The growth benefit of Ca and Mg to plants in an acid Inceptisol was also evaluated. In this experiment soil exchangeable Ca:Mg ratios were adjusted to reach 10 and 60 % base saturation, controlled by different amounts of CaCl2 or MgCl2 (at proportions from 100:0 up to 0:100), without altering the soil pH level. The low (10 %) and adequate (60 %) base saturation were used to examine how plant roots respond to Al at distinct (Ca + Mg)/Al ratios, as if they were growing in soils with distinct acidity levels. Negative and positive control treatments consisted of absence (under native soil or undisturbed conditions) or presence of lime (CaCO3) to reach 10 and 60 % base saturation, respectively. It was observed that in the absence of Aluminum, Cu, Zn, Co and Sn were toxic even at a low concentration (25 µmol L-1), while the effect of Mn, Ba, Sr and Mg was positive or absent on soybean root elongation when used in concentrations up to 100 µmol L-1. At a level of 10 µmol L-1 Al, root growth was only reverted to the level of control plants by the Mg treatment. Higher Tin doses led to a small alleviation of Al rhizotoxicity, while the other cations reduced root growth or had no effect. This is an indication that the Mg effect is ion-specific and not associated to an electrostatic protection mechanism only, since all ions were divalent and used at low concentrations. An increased exchangeable Ca:Mg ratio (at constant soil pH) in the acid soil almost doubled the soybean shoot and root dry matter even though treatments did not modify soil pH and exchangeable Al3+. This indicates a more efficient alleviation of Al toxicity by Mg2+ than by Ca2+. The reason for the positive response to Mg2+ was not the supply of a deficient nutrient because CaCO3 increased soybean growth by increasing soil pH without inducing Mg2+ deficiency. Both in hydroponics and acid soil, the reduction in Al toxicity was accompanied by a lower Al accumulation in plant tissue, suggesting a competitive cation absorption and/or exclusion of Al from plant tissue stimulated by an Mg-induced physiological mechanism.

Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: Results from the randomized controlled I-COME Trial

Introduction: Imatinib trough plasma concentrations (Cmin) have been correlated with treatment response in chronic myeloid leukemia (CML) patients. The use of Cmin monitoring for optimizing imatinib dosage (therapeutic drug monitoring [TDM]) is therefore proposed for patients with unsatisfying response or tolerance ("rescue TDM"). A cycle of "routine TDM" for dosage individualization could also be beneficial to prevent unfavorable events, yet its clinical usefulness has not been evaluated. We aimed to assess prospectively whether a "routine TDM" intervention targeting imatinib Cmin of 1000 ng/mL (tolerance, 750-1500 ng/mL) could improve efficacy, tolerance, and persistence on treatment compared with "rescue TDM" use only. Patients (or Materials) and Methods: The Swiss Imatinib COncentration Monitoring Evaluation (I-COME) study was a multicenter randomized controlled trial (ISRCTN31181395). Adult patients in chronic or accelerated phase CML receiving imatinib ≤5 years were eligible. Patients were randomly (1:1) allocated to receive "routine TDM" intervention or to serve as controls with access only to "rescue TDM". All had 1-year follow-up. The primary endpoint was a combined efficacy-safety outcome (failure- and toxicity-free survival without imatinib discontinuation), analyzed in intention-to-treat. Results: Among 56 CML recruited patients, 55 had their molecular and cytogenetic response measured. 14/27 of patients receiving "routine TDM" (52% [33%-71%]) remained event-free versus 16/28 of control patients with "rescue TDM" only (57% [39%-75%]; P=0.69). In the "routine TDM" group, dosage recommendations were adopted entirely in 50% of patients (median Cmin at study end, 895 ng/mL; CV = 33%). These patients had fewer unfavorable events (28% [5%-52%]) compared with patients not receiving the advised dosage (77% [54%-99%]; P = 0.03; median Cmin at study end, 648 ng/mL; CV = 38%). Conclusion: This first prospective target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" of imatinib, especially due to a small patient number and limited prescriber's adherence to dosage recommendations. Nevertheless, the patients receiving the advised dosage more often met target concentrations and the combined outcome (efficacy, tolerance, and persistence). A cycle of routine TDM could thus be favorable, at least in patients eligible for dosage adjustment. Its usefulness should, however, be further confirmed in larger trials.

The geographical concentration of industry across Spanish Regions, 1856-1995

New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

Etude de l'activation et de l'inactivation pH-dépendantes des canaux ASICs (Acide-Sensing Ion Channels)

RESUME: Etude de l'activation et de l'inactivation pH-dépendantes des canaux ASICs (Acid-Sensing Ion Channels) Benoîte BARGETON, Département de Pharmacologie et de Toxicologie, Université de Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Suisse Les canaux sodiques ASICs (Acid-Sensing Ion Channels) participent à la signalisation neuronale dans les systèmes nerveux périphérique et central. Ces canaux non voltage dépendants sont impliqués dans l'apprentissage, l'expression de la peur, la neurodégénération consécutive à une attaque cérébrale et la douleur. Les bases moléculaires sous-tendant leur activité ne sont pas encore totalement comprises. Ces canaux sont activés par une acidification du milieu extracellulaire et régulés, entre autres, par des ions tels que le Ca2+, le Zn2+ et le CI". La cristallisation de ASIC inactivé a été publiée. Le canal est un trimére de sous-unités identiques ou homologues. Chaque sous-unité a été décrite en analogie à un avant bras, un poignet et une main constituée d'un pouce, d'un doigt, d'une articulation, une boule β et une paume. Nous avons appliqué une approche bioinformatique systématique pour identifier les pH senseurs putatifs de ASICIa. Le rôle des pH senseurs putatifs a été testé par mutagénèse dirigée et des modifications chimiques combinées à une analyse fonctionnelle afin de comprendre comment les variations de ρ H ouvrent ces canaux. Les pH senseurs sont des acides aspartiques et glutamiques éparpillés sur la boucle extracellulaire suggérant que les changements de pH contrôlent l'activation et l'inactivation de ASIC en (dé)protonant ces résidus en divers endroits de la protéine. Par exemple lors de l'activation, la protonation des résidus à l'interface entre le pouce, la boule β et le doigt d'une même sous-unité induit un mouvement du pouce vers la bouie β et le doigt. De même lors de l'inactivation du canal les paumes des trois sous-unités formant une cavité se rapprochent. D'après notre approche bioinformatique, aucune histidine n'est impliquée dans la détection des variations de pH extracellulaire c'est-à-dire qu'aucune histidine ne serait un pH-senseur. Deux histidines de ASIC2a lient le Zn2+ et modifient l'affinité apparente du canal pour les protons. Une seule des deux est conservée parmi tous les ASICs, hASICIa H163. Elle forme un réseau de liaison hydrogène avec ses voisins conservés. L'étude détaillée de ce domaine, Pinterzone, montre son importance dans l'expression fonctionnelle des canaux. La perturbation de ce réseau par l'introduction d'un résidu hydrophobe (cystéine) par mutagénèse dirigée diminue l'expression du canal à la membrane plasmique. La modification des cystéines introduites par des réactifs spécifiques aux groupements sulfhydryle inhibe les canaux mutés en diminuant leur probabilité d'ouverture. Ces travaux décrivent les effets de l'acidification du milieu extracellulaire sur les canaux ASICs. ABSTRACT: Study of pH-dependent activation and inactivation of ASIC channels Benoîte BARGETON, Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, CH-1G05 Lausanne, Switzerland The ASIC (Acid-Sensing Ion Channels) sodium channels are involved in neuronal signaling in the central and peripheral nervous system. These non-voltage-gated channels are involved in learning, the expression of fear, neurodegeneration after ischemia and pain sensation. The molecular bases underlying their activity are not yet fully understood. ASICs are activated by extracellular acidification and regulated, eg by ions such as Ca2+, the Zn2+ and CI". The crystallization of inactivated ASIC has been published. The channel is a trimer of identical or homologous subunits. Each subunit has been described in analogy to a forearm, wrist and hand consisting of a thumb, a finger, a knuckle, a β-ball and a palm. We applied a systematic computational approach to identify putative pH sensor(s) of ASICIa. The role of putative pH sensors has been tested by site-directed mutagenesis and chemical modification combined with functional analysis in order to understand how changes in pH open these channels. The pH sensors are aspartic and glutamic acids distributed throughout the extracellular loop, suggesting that changes in pH control activation and inactivation of ASIC by protonation / deprotonation of many residues in different parts of the protein. During activation the protonation of various residues at the interface between the finger, the thumb and the β-ball induces the movement of the thumb toward the finger and the β-ball. During inactivation of the channel the palms of the three subunits forming a cavity approach each other. No histidine has been shown to be involved in extracellular pH changes detection, i.e. no histidine is a pH- sensor. Two histidines of ASIC2 bind Zn2+ and alter the apparent affinity of channel for protons. Only one of the two His is conserved among all ASICs, hASICIa H163. This residue is part of a network of hydrogen bonding with its conserved neighbors. The detailed study of this area, the interzone, shows its importance in the functional expression of ASICs. Disturbance of this network by the introduction of hydrophobic residues decreases the cell surface channel expression. Chemical modification of the introduced cysteines by thiol reactive compounds inhibits the mutated channels by a reduction of their open probability. These studies describe the effects of extracellular acidification on ASICs. RESUME GRAND PUBLIC: Etude de l'activation et de l'inactivation pH-dépendantes des canaux ASICs (Acid-Sensing Ion Channels) Benoîte BARGETON, Département de Pharmacologie et de Toxicologie, Université de Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Suisse La transmission synaptique est un processus chimique entre deux neurones impliquant des neurotransmetteurs et leurs récepteurs. Un dysfonctionnement de certains types de synapses est à l'origine de beaucoup de troubles nerveux, tels que certaine forme d'épilepsie et de l'attention. Les récepteurs des neurotransmetteurs sont de très bonnes cibles thérapeutiques dans de nombreuses neuropathologies. Les canaux ASICs sont impliqués dans la neurodégénération consécutive à une attaque cérébrale et les bloquer pourraient permettre aux patients d'avoir moins de séquelles. Les canaux ASICs sont des détecteurs de l'acidité qui apparaît lors de situations pathologiques comme l'ischémie et l'inflammation. Ces canaux sont également impliqués dans des douleurs. Cibler spécifiquement ces canaux permettrait d'avoir de nouveaux outils thérapeutiques car à l'heure actuelle l'inhibiteur de choix, l'amiloride, bloque beaucoup d'autres canaux empêchant son utilisation pour bloquer les ASICs. C'est pourquoi il faut connaître et comprendre les bases moléculaires du fonctionnement de ces récepteurs. Les ASICs formés de trois sous-unités détectent les variations de l'acidité puis s'ouvrent transitoirement pour laisser entrer des ions chargés positivement dans la cellule ce qui active la signalisation neuronale. Afin de comprendre les bases moléculaires de l'activité des ASICs nous avons déterminé les sites de liaison des protons (pH-senseurs), ligands naturels des ASICs et décrit une zone importante pour l'expression fonctionnelle de ces canaux. Grâce à une validation systématique de résultats obtenus en collaboration avec l'Institut Suisse de Bioinformatique, nous avons décrit les pH-senseurs de ASICIa. Ces résultats, combinés à ceux d'autres groupes de recherche, nous ont permis de mieux comprendre comment les ASICs sont ouverts par une acidification du milieu extracellulaire. Une seconde étude souligne le rôle structural crucial d'une région conservée parmi tous les canaux ASICs : y toucher c'est diminuer l'activité de la protéine. Ce domaine permet l'harmonisation des changements dus à l'acidification du milieu extracellulaire au sein d'une même sous-unité c'est-à-dire qu'elle participe à l'induction de l'inactivation due à l'activation du canal Cette étude décrit donc quelle région de la protéine atteindre pour la bloquer efficacement en faisant une cible thérapeutique de choix.

Majority carrier capture cross section determination in the large deep trap concentration cases

A method to determine the thermal cross section of a deep level from capacitance measurements is reported. The results enable us to explain the nonexponential behavior of the capacitance versus capture time when the trap concentration is not negligible with respect to that of the shallow one, and the Debye tail effects are taken into account. A figure of merit for the nonexponential behavior of the capture process is shown and discussed for different situations of doping and applied bias. We have also considered the influence of the position of the trap level"s energy on the nonexponentiality of the capture transient. The experimental results are given for the gold acceptor level in silicon and for the DX center in Al0.55 Ga0.45As, which are in good agreement with the developed theory.

Extraction and concentration of biogenic calcium oxalate from plant leaves

The objective of this study was to extract and concentrate calcium oxalate (CaOx) crystals from plant leaves that form the above mentioned crystals. The chemical and physical studies of CaOx from plant to be performed depend on an adequate amount of the crystals. The plant used in this study was croton (Codiaeum variegatum). The leaves were ground in a heavy duty blender and sieved through a 0.20 mm sieve. The suspension obtained was suspended in distilled water. The crystals were concentrated at the bottom of a test tube. The supernatant must be washed until it is free of plant pigments and other organic substances. Biogenic CaOx crystals have well-defined and sharp peaks, indicating very high crystallinity. Moreover, the CaOx crystals were not damaged during the extraction procedure, as can be seen on the scanning electron microscope images. The porposed method can be considered efficient to extract and concentrate biogenic calcium oxalate.