Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like... more Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon® VA 64 at 10–30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC...
In vitro-expanded bone marrow stromal cells (BMSCs) have long been proposed for the treatment of ... more In vitro-expanded bone marrow stromal cells (BMSCs) have long been proposed for the treatment of complex bone-related injuries because of their inherent potential to differentiate into multiple skeletal cell types, modulate inflammatory responses, and support angiogenesis. Although a wide variety of methods have been used to expand BMSCs on a large scale by using good manufacturing practice (GMP), little attention has been paid to whether the expansion procedures indeed allow the maintenance of critical cell characteristics and potency, which are crucial for therapeutic effectiveness. Here, we described standard procedures adopted in our facility for the manufacture of clinical-grade BMSC products with a preserved capacity to generate bone in vivo in compliance with the Brazilian regulatory guidelines for cells intended for use in humans. Bone marrow samples were obtained from trabecular bone. After cell isolation in standard monolayer flasks, BMSC expansion was subsequently perform...
International journal of radiation biology, Jul 10, 2017
In the present work, femur diaphysis of rats, treated with two different chemotherapy drugs, AC (... more In the present work, femur diaphysis of rats, treated with two different chemotherapy drugs, AC (doxorubicin + cyclophosphamide) and TC (docetaxel + cyclophosphamide) were evaluated by 3D morphological analysis using synchrotron radiation microtomography. Wistar rats were classified into three groups. One group received doses of docetaxel and cyclophosphamide (G1) - TC regimen; another group received doses of doxorubicin and cyclophosphamide (G2) - AC regimen; while control group (G0) received no further treatment. 3D tomographic images of the rat's femurs were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the ELETTRA Synchrotron Laboratory in Trieste, Italy, using monochromatic x-rays with resolution of 9 µm. It could be shown that the treatment caused significant differences in morphological parameters measured from the 3D images of femur diaphysis of rats, among the studied groups, complementing previous study using stereological methods, bioc...
The recent years advancements in microtomography have increased the achievable resolution and con... more The recent years advancements in microtomography have increased the achievable resolution and contrast, making this relatively inexpensive and a widely available technology, potentially useful for studies of insect's internal morphology. Phase Contrast X-Ray Synchrotron Microtomography (SR-PhC-μCT) is a non-destructive technique that allows the microanatomical investigations of Rhodnius prolixus, one of the most important insect vectors of Trypanosoma cruzi, the etiologic agent of Chagas' disease. In Latin America, vector control is the most useful method to prevent Chagas' disease, and a detailed knowledge of R. prolixus' interior structures is crucial for a better understanding of their function and evolution. Traditionally, in both biological morphology and anatomy, the internal structures of whole organisms or parts of them are accessed by dissecting or histological serial sectioning; so studying the internal structures of R. prolixus' head using SR-PhC-μCT i...
ABSTRACT In recent years, new techniques have been developed for the analysis of bone matrix. Two... more ABSTRACT In recent years, new techniques have been developed for the analysis of bone matrix. Two of the most common technologies that make use of X-rays are X-ray microfluorescence (μXRF) and X-ray absorption microtomography (μCT). μXRF is a powerful analytical tool for the spectroscopic determination of almost all elements (Z > 13) present in a sample. μCT is a nondestructive technique, which can be used to create cross sections of complex objects.In this work, both techniques were applied to bones to evaluate possible structural and elemental modifications caused by chemotherapy procedure. Ten adult female Wistar rats, clinically healthy, divided randomly into two groups: treated group (called G1) received doses of docetaxel and cyclophosphamide drugs, while control group (called G0) was not treated. The elemental distribution of Ca and morphometric parameters, cortical porosity and bone volume-total tissue volume ratio in femur head, was investigated using μXRF and μCT, respectively, with the aim of helping to obtain a better understanding of the side effects caused by chemotherapy treatment for breast cancer. Calcium distribution maps were obtained by μXRF in the X-ray fluorescence beamline at the Brazilian Synchrotron Light Laboratory. Morphometric parameters were calculated from three-dimensional microtomographic images carried out at the Synchrotron Radiation on Medical Physics beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. As a result of this study using μXRF, Ca levels show a significant decrease in treated bones in comparison with the control group. From μCT analysis, bone volume-total tissue volume ratio shows a tendency to decrease, while cortical porosity shows significant increase in bones from G1 group.
We have used phase-contrast X-ray microtomography (PPC-mCT) to study the head of the blood-feedin... more We have used phase-contrast X-ray microtomography (PPC-mCT) to study the head of the blood-feeding bug, Rhodniusprolixus, whichisoneofthemostimportantinsectvectorof Trypanosomacruzi, ethiologic agentofChagasdiseaseinLatinAmerica.Imagesreconstructedfromphase-retrievedprojections processedby ANKA phase are comparedtothoseobtainedthroughdirecttomographicreconstructionof the flat-field-correctedtransmissionradiographs.Itshouldbenotedthattherelativelocationsofthe importantmorphologicalinternalstructuresareobservablewithaprecisionthatisdifficulttoobtain withoutthephaseretrievalapproach
2009 IEEE Nuclear Science Symposium Conference Record (NSS/MIC), 2009
We investigated the feasibility of the micro computed tomography dual-energy imaging to map of le... more We investigated the feasibility of the micro computed tomography dual-energy imaging to map of lead deposition inside bone. Femora of Wistar rats were imaged at the SYRMEP beamline at the ELETTRA synchrotron facility at Trieste, Italy, using two different energies, one just below (15.75 keV) and other just above (16.10 keV) the L-edge absorption energy of lead. By utilizing dual-energy
ABSTRACT Recently some developments in a large number of investigative techniques have been made ... more ABSTRACT Recently some developments in a large number of investigative techniques have been made with the objective to obtain a micrometer spatial resolution imaging of elemental concentrations. The X-ray microfluorescence analysis (µXRF) is one of those techniques which is based on the localized excitation of a small area on the surface of sample, providing information of all elements contained in the material under study.
ABSTRACT Microporosities play important biologic and mechanical roles on health. One of the side ... more ABSTRACT Microporosities play important biologic and mechanical roles on health. One of the side effects caused by some chemotherapy drugs is the induction of amenorrhea, temporary or not, in premenopausal women, with a consequent decrease in estrogen production, which can lead to cortical bone changes. In the present work, the femur diaphysis of rats treated with chemotherapy drugs were evaluated by 3D morphometric parameters using synchrotron radiation microtomography. Control animals were also evaluated for comparison. The 3D tomographic images were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the ELETTRA Synchrotron Laboratory in Trieste, Italy. Results showed significant differences in morphometric parameters measured from the 3D images of femur diaphysis of rats.
... Anderson Alvarenga de Moura Meneses a , Corresponding Author Contact Information , E-mail The... more ... Anderson Alvarenga de Moura Meneses a , Corresponding Author Contact Information , E-mail The Corresponding Author , Alessandro Giusti b , André Pereira de Almeida c , Liebert Parreira Nogueira c , Delson Braz c , Regina Cely Barroso d and Carlos Eduardo deAlmeida a. ...
Synchrotron Radiation (SR) X-Ray micro-Computed Tomography (µCT) enables magnified images that mi... more Synchrotron Radiation (SR) X-Ray micro-Computed Tomography (µCT) enables magnified images that might be used as a non-invasive and non-destructive technique with a high space resolution for the qualitative and quantitative analysis of images. The research on applications of segmentation algorithms to SR-µCT is an open problem, due to the interesting and well-known characteristics of SR images for visualization, such as
In this work we investigated the consequences of irradiation in the femur of rats to a radiation ... more In this work we investigated the consequences of irradiation in the femur of rats to a radiation dose of 5 Gy. Three different sites in femur specimens were imaged using synchrotron radiation computed microtomography to assess trabecular bone microarchitecture: femur head, distal metaphysis and distal epiphysis. Histomorphometric quantification was extracted directly from the 3D tomographic images using synchrontron radiation. The
2012 IEEE Nuclear Science Symposium and Medical Imaging Conference Record (NSS/MIC), 2012
ABSTRACT The most used treatment strategies for breast cancer (BC) are surgery, chemotherapy, and... more ABSTRACT The most used treatment strategies for breast cancer (BC) are surgery, chemotherapy, and/or radiotherapy. Premenopausal women undergoing adjuvant chemotherapy BC treatment have significant bone loss from the first year after the treatment. This high bone mineral density loss can lead to an increased risk of fractures. Doxorubicin associated with Cyclophosphamide (AC) is a multidrug widely used for BC treatment, although this association can cause severe side effects. Today it is been discussed the use of the Docetaxel and cyclophosphamide (TC) association for BC treatment. The influence on the bone during chemotherapy regimens that include taxanes, like docetaxel, is unknown. Data from the “Women's Health Initiative” show that postmenopausal BC survivors have a 15% greater risk of developing fractures than women without a history of BC. In this study, it was evaluated parameters involved in osteoporosis when rats were subjected to a chemotherapy regimen (TC) and/or irradiation (IR). Female Wistar rats, 03 months old, were divided into 3 groups: control, TC+IR (G1) and AC+IR (G2). The animals were euthanized 5 after months the end of treatment and their femurs were excised and dissected. Sections of 10 μm thick were used for μXRF analysis at the National Laboratory of Synchrotron Light. The uteri of these rats were collected and weighed Statistical analyzes were performed using GraphPad Prism, and values were compared using ANOVA and Tukey post-hoc test. The obtained results showed that animals from G2 had a significant reduction (p
Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like... more Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon® VA 64 at 10–30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC...
In vitro-expanded bone marrow stromal cells (BMSCs) have long been proposed for the treatment of ... more In vitro-expanded bone marrow stromal cells (BMSCs) have long been proposed for the treatment of complex bone-related injuries because of their inherent potential to differentiate into multiple skeletal cell types, modulate inflammatory responses, and support angiogenesis. Although a wide variety of methods have been used to expand BMSCs on a large scale by using good manufacturing practice (GMP), little attention has been paid to whether the expansion procedures indeed allow the maintenance of critical cell characteristics and potency, which are crucial for therapeutic effectiveness. Here, we described standard procedures adopted in our facility for the manufacture of clinical-grade BMSC products with a preserved capacity to generate bone in vivo in compliance with the Brazilian regulatory guidelines for cells intended for use in humans. Bone marrow samples were obtained from trabecular bone. After cell isolation in standard monolayer flasks, BMSC expansion was subsequently perform...
International journal of radiation biology, Jul 10, 2017
In the present work, femur diaphysis of rats, treated with two different chemotherapy drugs, AC (... more In the present work, femur diaphysis of rats, treated with two different chemotherapy drugs, AC (doxorubicin + cyclophosphamide) and TC (docetaxel + cyclophosphamide) were evaluated by 3D morphological analysis using synchrotron radiation microtomography. Wistar rats were classified into three groups. One group received doses of docetaxel and cyclophosphamide (G1) - TC regimen; another group received doses of doxorubicin and cyclophosphamide (G2) - AC regimen; while control group (G0) received no further treatment. 3D tomographic images of the rat's femurs were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the ELETTRA Synchrotron Laboratory in Trieste, Italy, using monochromatic x-rays with resolution of 9 µm. It could be shown that the treatment caused significant differences in morphological parameters measured from the 3D images of femur diaphysis of rats, among the studied groups, complementing previous study using stereological methods, bioc...
The recent years advancements in microtomography have increased the achievable resolution and con... more The recent years advancements in microtomography have increased the achievable resolution and contrast, making this relatively inexpensive and a widely available technology, potentially useful for studies of insect's internal morphology. Phase Contrast X-Ray Synchrotron Microtomography (SR-PhC-μCT) is a non-destructive technique that allows the microanatomical investigations of Rhodnius prolixus, one of the most important insect vectors of Trypanosoma cruzi, the etiologic agent of Chagas' disease. In Latin America, vector control is the most useful method to prevent Chagas' disease, and a detailed knowledge of R. prolixus' interior structures is crucial for a better understanding of their function and evolution. Traditionally, in both biological morphology and anatomy, the internal structures of whole organisms or parts of them are accessed by dissecting or histological serial sectioning; so studying the internal structures of R. prolixus' head using SR-PhC-μCT i...
ABSTRACT In recent years, new techniques have been developed for the analysis of bone matrix. Two... more ABSTRACT In recent years, new techniques have been developed for the analysis of bone matrix. Two of the most common technologies that make use of X-rays are X-ray microfluorescence (μXRF) and X-ray absorption microtomography (μCT). μXRF is a powerful analytical tool for the spectroscopic determination of almost all elements (Z > 13) present in a sample. μCT is a nondestructive technique, which can be used to create cross sections of complex objects.In this work, both techniques were applied to bones to evaluate possible structural and elemental modifications caused by chemotherapy procedure. Ten adult female Wistar rats, clinically healthy, divided randomly into two groups: treated group (called G1) received doses of docetaxel and cyclophosphamide drugs, while control group (called G0) was not treated. The elemental distribution of Ca and morphometric parameters, cortical porosity and bone volume-total tissue volume ratio in femur head, was investigated using μXRF and μCT, respectively, with the aim of helping to obtain a better understanding of the side effects caused by chemotherapy treatment for breast cancer. Calcium distribution maps were obtained by μXRF in the X-ray fluorescence beamline at the Brazilian Synchrotron Light Laboratory. Morphometric parameters were calculated from three-dimensional microtomographic images carried out at the Synchrotron Radiation on Medical Physics beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. As a result of this study using μXRF, Ca levels show a significant decrease in treated bones in comparison with the control group. From μCT analysis, bone volume-total tissue volume ratio shows a tendency to decrease, while cortical porosity shows significant increase in bones from G1 group.
We have used phase-contrast X-ray microtomography (PPC-mCT) to study the head of the blood-feedin... more We have used phase-contrast X-ray microtomography (PPC-mCT) to study the head of the blood-feeding bug, Rhodniusprolixus, whichisoneofthemostimportantinsectvectorof Trypanosomacruzi, ethiologic agentofChagasdiseaseinLatinAmerica.Imagesreconstructedfromphase-retrievedprojections processedby ANKA phase are comparedtothoseobtainedthroughdirecttomographicreconstructionof the flat-field-correctedtransmissionradiographs.Itshouldbenotedthattherelativelocationsofthe importantmorphologicalinternalstructuresareobservablewithaprecisionthatisdifficulttoobtain withoutthephaseretrievalapproach
2009 IEEE Nuclear Science Symposium Conference Record (NSS/MIC), 2009
We investigated the feasibility of the micro computed tomography dual-energy imaging to map of le... more We investigated the feasibility of the micro computed tomography dual-energy imaging to map of lead deposition inside bone. Femora of Wistar rats were imaged at the SYRMEP beamline at the ELETTRA synchrotron facility at Trieste, Italy, using two different energies, one just below (15.75 keV) and other just above (16.10 keV) the L-edge absorption energy of lead. By utilizing dual-energy
ABSTRACT Recently some developments in a large number of investigative techniques have been made ... more ABSTRACT Recently some developments in a large number of investigative techniques have been made with the objective to obtain a micrometer spatial resolution imaging of elemental concentrations. The X-ray microfluorescence analysis (µXRF) is one of those techniques which is based on the localized excitation of a small area on the surface of sample, providing information of all elements contained in the material under study.
ABSTRACT Microporosities play important biologic and mechanical roles on health. One of the side ... more ABSTRACT Microporosities play important biologic and mechanical roles on health. One of the side effects caused by some chemotherapy drugs is the induction of amenorrhea, temporary or not, in premenopausal women, with a consequent decrease in estrogen production, which can lead to cortical bone changes. In the present work, the femur diaphysis of rats treated with chemotherapy drugs were evaluated by 3D morphometric parameters using synchrotron radiation microtomography. Control animals were also evaluated for comparison. The 3D tomographic images were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the ELETTRA Synchrotron Laboratory in Trieste, Italy. Results showed significant differences in morphometric parameters measured from the 3D images of femur diaphysis of rats.
... Anderson Alvarenga de Moura Meneses a , Corresponding Author Contact Information , E-mail The... more ... Anderson Alvarenga de Moura Meneses a , Corresponding Author Contact Information , E-mail The Corresponding Author , Alessandro Giusti b , André Pereira de Almeida c , Liebert Parreira Nogueira c , Delson Braz c , Regina Cely Barroso d and Carlos Eduardo deAlmeida a. ...
Synchrotron Radiation (SR) X-Ray micro-Computed Tomography (µCT) enables magnified images that mi... more Synchrotron Radiation (SR) X-Ray micro-Computed Tomography (µCT) enables magnified images that might be used as a non-invasive and non-destructive technique with a high space resolution for the qualitative and quantitative analysis of images. The research on applications of segmentation algorithms to SR-µCT is an open problem, due to the interesting and well-known characteristics of SR images for visualization, such as
In this work we investigated the consequences of irradiation in the femur of rats to a radiation ... more In this work we investigated the consequences of irradiation in the femur of rats to a radiation dose of 5 Gy. Three different sites in femur specimens were imaged using synchrotron radiation computed microtomography to assess trabecular bone microarchitecture: femur head, distal metaphysis and distal epiphysis. Histomorphometric quantification was extracted directly from the 3D tomographic images using synchrontron radiation. The
2012 IEEE Nuclear Science Symposium and Medical Imaging Conference Record (NSS/MIC), 2012
ABSTRACT The most used treatment strategies for breast cancer (BC) are surgery, chemotherapy, and... more ABSTRACT The most used treatment strategies for breast cancer (BC) are surgery, chemotherapy, and/or radiotherapy. Premenopausal women undergoing adjuvant chemotherapy BC treatment have significant bone loss from the first year after the treatment. This high bone mineral density loss can lead to an increased risk of fractures. Doxorubicin associated with Cyclophosphamide (AC) is a multidrug widely used for BC treatment, although this association can cause severe side effects. Today it is been discussed the use of the Docetaxel and cyclophosphamide (TC) association for BC treatment. The influence on the bone during chemotherapy regimens that include taxanes, like docetaxel, is unknown. Data from the “Women's Health Initiative” show that postmenopausal BC survivors have a 15% greater risk of developing fractures than women without a history of BC. In this study, it was evaluated parameters involved in osteoporosis when rats were subjected to a chemotherapy regimen (TC) and/or irradiation (IR). Female Wistar rats, 03 months old, were divided into 3 groups: control, TC+IR (G1) and AC+IR (G2). The animals were euthanized 5 after months the end of treatment and their femurs were excised and dissected. Sections of 10 μm thick were used for μXRF analysis at the National Laboratory of Synchrotron Light. The uteri of these rats were collected and weighed Statistical analyzes were performed using GraphPad Prism, and values were compared using ANOVA and Tukey post-hoc test. The obtained results showed that animals from G2 had a significant reduction (p
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Papers by Liebert P. Nogueira