Maria Cristina Silva

Imatinib treatment duration is related to decreased estimated glomerular filtration rate in chronic myeloid leukemia patients

BACKGROUND We analyzed the incidence of acute kidney injury and chronic renal failure in chronic myeloid leukemia (CML) patients using imatinib and investigated whether there is a relation between duration of imatinib therapy and decrease in estimated glomerular filtration rate (GFR). PATIENTS AND METHODS One hundred five CML patients on imatinib therapy were enrolled. Creatinine, urea, uric acid, and potassium measurements from imatinib treatment onset until the end of follow-up (median 4.5 years) were included in the analysis. GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS During follow-up, 7% of patients developed acute kidney injury; creatinine levels returned to baseline in only one of them. According to the regression equation, the mean baseline value of the estimated GFR was 88.9 ml/min/1.73 m(2). Estimated GFR decreased significantly with imatinib treatment duration; the mean decrease per year was 2.77 ml/min/1.73 m(2) (P < 0.001); 12% of patients developed chronic renal failure. Age, hypertension, and a history of chronic renal failure or interferon usage were not significantly related to the mean decrease in the estimated GFR over time. CONCLUSION The introduction of imatinib therapy in nonclinical trial CML patients is associated with potentially irreversible acute renal injury, and the long-term treatment may cause a clinically relevant decrease in the estimated GFR.

Computational Enzymology and Organophosphorus Degrading Enzymes: Promising Approaches Toward Remediation Technologies of Warfare Agents and Pesticides

The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.

Immobilization of soybean peroxidase on silica-coated magnetic particles: a magnetically recoverable biocatalyst for pollutant removal

In this work we investigated the enzymatic degradation of ferulic acid, a model pollutant, by free and immobilized soybean peroxidase. With the aim of developing greener catalysts, we proposed the synthesis of a magnetic catalyst prepared via immobilization of soybean peroxidase onto a magnetic nanosupport by covalent attachment. The immobilization of soybean peroxidase was carried out using magnetite nanoparticles modified with amino groups as support. The magnetite particles were characterized before and after chemical modification by XRD, SEM and TEM analysis. The characterization data indicated that the Fe3O4–SiO2 nanoparticles were successfully synthetized. The high immobilization yield was obtained in only 1 hour of reaction (89.23%). The resulting nanobiocatalyst (enzyme load 5.25 U) was able to remove 99.67 ± 0.10% of ferulic acid in comparison to 57.67 ± 0.27% for free enzyme under the same reaction conditions. The immobilized peroxidase could easily be separated under a magnetic field and reused. On the basis of these results, we concluded that the prepared magnetic nanoparticles can be considered a high-performance nanocatalyst for environmental remediation.

Combined experimental and theoretical study on the removal of pollutant compounds by peroxidases: affinity and reactivity toward a bioremediation catalyst

Water pollution is a significant and growing problem throughout the world, especially in developing countries. In order to minimize environmental problems, catalysts have increasingly been designed to remove pollutants from the water. In an attempt to innovate by the creation of new low-cost alternatives to efficiently remove pollutants, the enzymatic treatment has been intensely studied for this purpose. Reactions catalyzed by enzymes are able to perform specific treatments, commonly with high rates of the final products. With this, the enzyme, peroxidase, is a promising candidate as a bioremediation catalyst. The efficiency of oxidoreductive enzymes, such as horseradish peroxidase (HRP) and soybean peroxidase (SP) have been studied, given that their performance depends on the substrate. In this investigation, experimental techniques and theoretical calculations have been employed in order to investigate the oxidative process for the ferulic acid and bromophenol blue dyes, performed by HRP and SP. Both enzymes showed a comparable behavior with respect to ferulic acid substrate. On the other hand, by utilizing bromophenol blue dye as a substrate, the behavior of the employed catalysts was significantly different. Experimental data have shown that HRP was more active toward bromophenol blue when compared to ferulic acid, being more rapidly degraded by the HRP enzyme. This tendency was confirmed by our theoretical docking, PM6 semi-empirical method, and DFT calculation results, in which the interaction, binding energies, and transition states were determined.

The duration of the use of imatinib mesylate is only weakly related to elevated BNP levels in chronic myeloid leukaemia patients

Cardiotoxicity has been feared as a potential side effect of imatinib therapy. Studies with short‐term follow‐up failed to identify an excess of cardiac events, but longer‐term observations are needed to more definitely exclude this adverse effect. This study was designed to assess the cardiac effects of imatinib in patients under long‐term treatment. We included 90 chronic myeloid leukaemia (CML) patients under imatinib therapy for a median treatment time of 3.3 years (mean age 48.9 ± 15.1 years). Patients underwent clinical evaluation, electrocardiography, echocardiography (two‐dimensional, colour flow, tissue Doppler and strain imaging), brain natiuretic peptide (BNP) and troponin I measurements. Twenty healthy volunteers were included as a control group for strain measurements. The mean ejection fraction was 68 ± 7% and the median BNP level was 9.6 pg/ml (interquartile range [IQR] 5.7–17.0 pg/ml). Two patients had either an elevated BNP or a depressed ejection fraction (2.2%; 90%CI 0.9–6.8%). Most of troponin I measurements were lower than the detection limit, except for two patients. Longitudinal strain was similar to measurements in healthy controls. A weak relation was observed between log BNP and imatinib treatment duration and dose. There was no relation between these variables and left ventricle ejection fraction. In conclusion, matinib‐related cardiotoxicity is an uncommon event in CML patients, even during long‐term treatment. Therefore, its use should not be cause of great concern, and the usefulness of regular cardiac monitoring all patients while on imatinib therapy is questionable. Copyright

Enzymatic oxidation of phenolic compounds in coffee processing wastewater

Peroxidases can be used in the treatment of wastewater containing phenolic compounds. The effluent from the wet processing of coffee fruits contains high content of these pollutants and although some studies propose treatments for this wastewater, none targets specifically the removal of these recalcitrant compounds. This study evaluates the potential use of different peroxidase sources in the oxidation of caffeic acid and of total phenolic compounds in coffee processing wastewater (CPW). The identification and quantification of phenolic compounds in CPW was performed and caffeic acid was found to be the major phenolic compound. Some factors, such as reaction time, pH, amount of H2O2 and enzyme were evaluated, in order to determine the optimum conditions for the enzyme performance for maximum oxidation of caffeic acid. The turnip peroxidase (TPE) proved efficient in the removal of caffeic acid, reaching an oxidation of 51.05% in just 15 minutes of reaction. However, in the bioremediation of the CPW, the horseradish peroxidase (HRP) was more efficient with 32.70%±0.16 of oxidation, followed by TPE with 18.25%±0.11. The treatment proposed in this work has potential as a complementary technology, since the efficiency of the existing process is intimately conditioned to the presence of these pollutants.

The use of imatinib mesylate has no adverse effects on the heart function. Results of a pilot study in patients with chronic myeloid leukemia

To investigate cardiac effects of imatinib at an extended follow-up (median 12.4 months), 12 chronic myeloid leukemia patients underwent cardiac screening. No significant changes on the frequency of cardiovascular signs and symptoms, electrocardiographic abnormalities, echocardiographic measurements and BNP levels were observed. Median ejection fraction was 67% at baseline versus 68% at follow-up (median intra-patient change 0.5%). Median BNP levels were 8.3 versus 7.3pg/mL (median intra-patient change 0.2pg/mL). Troponin I measures were below the lower limit of detection, whereas strain measures were similar to healthy control. This pilot study suggests that it is probably safe to perform cardiac monitoring on an annual basis.

PLANT: A bibliographic database about medicinal plants

In this article we presented a bibliographical Database - PLANT, developed by the Library of the Pharmacy School from Universidade Federal de Minas Gerais (UFMG). From this database, it is possible to retrieve information on medicinal plants present in the Brazilian bibliography, which in great part are not indexed. The objective of PLANT is to contribute for the development of new herbal products, especially those with Brazilian plants.

Novel eco-friendly biocatalyst: soybean peroxidase immobilized onto activated carbon obtained from agricultural waste

The immobilization of enzymes is an excellent alternative to overcome the drawbacks of using these biocatalysts in free form. This process plays a significant role in cost-effective recovery, increased catalyst productivity and in simplifying process operations. After the soybean peroxidase (SP) extraction, a residue at high carbon and low ash content is generated. This residue was used as carbonaceous precursor for production of carbon activated (AC) with high surface area (1603 m2 g−1). The AC produced was used as support for SP immobilization. The immobilization of SP was evaluated in different time conditions, enzyme load, pH and temperature. The samples, before and after immobilization, were characterized by thermogravimetric analysis, elemental analysis composition, specific surface area, X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. In addition, repeated applications of immobilized biocatalyst were made in order to evaluate its operational stability and capacity to recover the reaction medium, in which was observed that after a decline in activity from the first to the second cycle, it remained constant until the tenth application. In the context, the process of material obtainment constitutes a clean route for the development of more sustainable biocatalysts capable of applications in various areas.

Evaluation of the protective effect of chemical additives in the oxidation of phenolic compounds catalysed by peroxidase

ABSTRACT The use of oxidoredutive enzymes in removing organic pollutants has been the subject of much research. The oxidation of phenolic compounds in the presence of chemical additives has been the focus of this study. In this investigation, the influence of the additives polyethylene glycol and Triton X-100 was evaluated in the phenol oxidation, caffeic acid, chlorogenic acid and total phenolic compounds present in coffee processing wastewater (CPW) at different pH values, performed by turnip peroxidase and peroxidase extracted from soybean seed hulls. The influence of these additives was observed only in the oxidation of phenol and caffeic acid. In the oxidation of other studied phenolic compounds, the percentage of oxidation remained unchanged in the presence of these chemical additives. In the oxidation of CPW in the presence of additives, no change in the oxidation of phenolic compounds was observed. Although several studies show the importance of evaluating the influence of additives on the behaviour of enzymes, this study found a positive response from the economic point of view for the treatment of real wastewater, since the addition of these substances showed no influence on the oxidation of phenolic compounds, which makes the process less costly.