Beatriz Silva Lima | Faculdade de Farmacia - Universidade de Lisboa (original) (raw)

Papers by Beatriz Silva Lima

Research paper thumbnail of Nitric oxide is involved in the mechanism for the antihypertension action of carvedilol

Acta Pharmacologica Sinica, 2006

【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure thr... more 【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure through a vasorelaxant effect mediated possibly by NO. We have shown that in the rat vas deferens(rvd) NO pathway potentiates the noradrenaline(NE)-release ...

Research paper thumbnail of Phytochemical, pre-clinical safety and efficacy evaluation of two Portuguese Asphodelus leaf extracts

Planta Medica, Dec 1, 2022

Research paper thumbnail of Identification of Marker Compounds and In Vitro Toxicity Evaluation of Two Portuguese Asphodelus Leaf Extracts

Molecules, Mar 4, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Bioguided Identification of Active Antimicrobial Compounds from Asphodelus bento-rainhae and Asphodelus macrocarpus Root Tubers

Pharmaceuticals

Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species,... more Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have traditionally been used in Portugal to treat inflammatory and infectious skin disorders. The present study aims to evaluate the in vitro antimicrobial activity of crude 70% and 96% hydroethanolic extracts of both medicinal plants, specifically against multidrug-resistant skin-related pathogens, to identify the involved marker secondary metabolites and also to assess the pre-clinical toxicity of these medicinal plant extracts. Bioguided fractionation of the 70% hydroethanolic extracts of both species using solvents of increasing polarity, namely diethyl ether (DEE: AbR-1, AmR-1), ethyl acetate (AbR-2, AmR-2) and aqueous (AbR-3, AmR-3) fractions, enabled the identification of the DEE fractions as the most active against all the tested Gram-positive microorganisms (MIC: 16 to 1000 µg/mL). Furthermore, phytochemical analyses using TLC...

Research paper thumbnail of Contribution to the Preclinical Safety Assessment of Lannea velutina and Sorindeia juglandifolia Leaves

Plants

Dried leaves of Lannea velutina A. Rich. and Sorindeia juglandifolia (A. Rich.) Planch. ex Oliv. ... more Dried leaves of Lannea velutina A. Rich. and Sorindeia juglandifolia (A. Rich.) Planch. ex Oliv. (family Anacardiaceae) are used in African traditional medicine. Although these medicinal plants have widespread use in the treatment of inflammatory diseases, there is no scientific data concerning their preclinical or clinical safety. This work aimed to investigate the phytochemical properties of the leaves of both species using HPLC-UV/DAD, as well as the in vivo oral repeated-dose toxicity of 70% hydroethanolic leaf extract of S. juglandifolia and the in vitro genotoxicity of 70% hydroethanolic leaf extracts of L. velutina and S. juglandifolia. Clinical signs of toxicity, body weight variations, and changes in food consumption, mortality, and blood biochemical parameters were monitored. Genotoxicity was assessed using the bacterial reverse mutation assay (Ames test) with and without metabolic activation, according to OECD guidelines. The obtained results showed the presence of gallic...

Research paper thumbnail of Monographic Quality Parameters and Genotoxicity Assessment of Asphodelus bento-rainhae and Asphodelus macrocarpus Root Tubers as Herbal Medicines

Plants

Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), an endemic species with relev... more Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), an endemic species with relevant interest due to conservation concerns, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have been traditionally used for culinary and medicinal purposes, mainly associated with skin infection and inflammation. The present study aims to establish the quality control criteria for the proper characterization of dried root tubers of both species as herbal substances, together with their preclinical safety assessments. Botanical identification using macroscopic and microscopic techniques and phytochemical evaluation/quantification of the main classes of marker secondary metabolites, including phenolic compounds (flavonoid, anthraquinone, condensed and hydrolysable tannin) and terpenoids were performed. Additionally, in vitro genotoxicity/mutagenicity was evaluated by Ames test. Evident morphological differences in the development of tubercles (3.5 × 1 cm in AbR and 8.7 × 1.4 cm in AmR)...

Research paper thumbnail of Anti‐inflammatory effect of Rosmarinic acid on a model of carrageenan‐induced paw edema

Research paper thumbnail of Rosmarinic acid reduces multiple organ failure in thermal injury and liver ischemia‐reperfusion injury

Research paper thumbnail of Effect of dietary n-3 PUFA from microalgae on blood, liver, brain, kidney and heart lipids

Research paper thumbnail of Rosmarinic Acid Attenuates Inflammatory-Induced Organ Injury in Thermal Injury and Liver Ischemia-Reperfusion-Injury

Research paper thumbnail of Microalgae a new promising omega 3 fatty acid source

N.M. Bandarra, D. Duarte, R. Pinto, C. Sampayo, M. Ramos, I. Batista, M.L. Nunes, A.P. Batista, A... more N.M. Bandarra, D. Duarte, R. Pinto, C. Sampayo, M. Ramos, I. Batista, M.L. Nunes, A.P. Batista, A. Raymundo, L. Gouveia, B.S. Lima (1) INRB/L-IPIMAR, Av. Brasília 1449-006 Lisboa, Portugal; (2), IMED.UL, Faculdade de Farmácia Universidade de Lisboa, Av das Forcas Armadas 1600 Lisboa, Portugal. (3) Núcleo de Investigação em Engenharia Alimentar e Biotecnologia, Instituto Piaget ISEIT de Almada, Quinta da Arreinela de Cima, 2800-305 Almada, Portugal; (4) Instituto Nacional de Engenharia e Tecnologia Industrial INETI-DER Unidade Biomassa, Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal

Research paper thumbnail of Rat skin physiology is modified by age

Journal Biomedical and Biopharmaceutical Research, 2012

Biomedical and Biopharmaceutical Research J o r n a l d e I n v e s t i g a ç ã o B i o m é d i c... more Biomedical and Biopharmaceutical Research J o r n a l d e I n v e s t i g a ç ã o B i o m é d i c a e B i o f a r m a c ê u t i c a Rat skin physiology is modified by age A Fisiologia da pele de rato é modificada pela idade 1-4

Research paper thumbnail of A Comprehensive Review on the Medicinal Plants from the Genus Asphodelus

Plants, 2018

Plant-based systems continue to play an essential role in healthcare, and their use by different ... more Plant-based systems continue to play an essential role in healthcare, and their use by different cultures has been extensively documented. Asphodelus L. (Asphodelaceae) is a genus of 18 species and of a total of 27 species, sub-species and varieties, distributed along the Mediterranean basin, and has been traditionally used for treating several diseases particularly associated with inflammatory and infectious skin disorders. The present study aimed to provide a general review of the available literature on ethnomedical, phytochemical, and biological data related to the genus Asphodelus as a potential source of new compounds with biological activity. Considering phytochemical studies, 1,8-dihydroxyanthracene derivatives, flavonoids, phenolic acids and triterpenoids were the main classes of compounds identified in roots, leaf and seeds which were correlated with their biological activities as anti-microbial, anti-fungal, anti-parasitic, cytotoxic, anti-inflammatory or antioxidant agents.

Research paper thumbnail of Phenol content, antioxidant and α- and β-glucosidase inhibitory activities of an Anacardium occidentale stem bark Traditional Herbal Preparation

Planta Medica, 2014

Introduction: Anacardium occidentale L., commonly known as cashew tree, has been traditionally us... more Introduction: Anacardium occidentale L., commonly known as cashew tree, has been traditionally used in several countries of Asia, Africa and America, due to its antihyperglycemic properties. Aim of work: To perform comparative studies between Traditional Herbal Preparation (THP) of A. occidentale stem bark red (AOR) and white (AOW) in order to assess their free radical scavenging, α- and β-glucosidase inhibition activities and total phenolic content. Methods: THP total phenol content was determined by the Folin-Ciocalteu method [1], using gallic acid as standard. Simultaneously, the free radical scavenging activity of the THPs was assessed with a 1,1-diphenyl-2-picrylhydrazine (DPPH) assay, using ascorbic acid as reference standard [2]. Moreover bioautographic assays with thin layer chromatography were performed for the detection of α- and β-glucosidase inhibitors [3]. Results: Total phenolic content was found to be 51.3 ± 1.6 and 58.0 ± 0.4 mg of gallic acid equivalent per gram of dried cashew stem bark in AOR and AOW THP, respectively. Concerning the free radical scavenging activity, IC50 value was 180.7 ± 6.7 µg/mL for the AOR THP and 143.8 ± 2.8 µg/mL for the AOW THP. Bioautography showed two chromatogram zones that were identified as α-glucosidase (Rf between 0.55 and 0.68) and β-glucosidase (Rf between 0.63 and 0.87) inhibitors in both THP. Conclusion: Assessed THP proved to be a source of natural antioxidants that may scavenge free radicals. According to data obtained from all experimental assays, AOW THP has higher antioxidant activity and total phenolic content than AOR THP. Moreover, extracts from both types of A. occidentale promoted inhibition of α- and β-glucosidase. Acknowledgements: This work was supported by grant Pest-OE/SAU/UI4013/2011 from Fundacao para a Ciencia e Tecnologia, Lisbon, Portugal. Keywords: Cashew stem bark, Traditional Herbal Preparation References: [1] Scalbert A, Monties B, Jannin G. Tannins in wood: comparison of different estimation methods. J Agricult Food Chem 1989; 37(5): 1324 – 1329. [2] Silva T, Camara C, Lins A, Barbosa-Filho J, Silva E, Freitas B, Santos F. Chemical composition and free radical scavenging activity of pollen loads from stingless bee Melipona subnitida Ducke. J Food Comp Anal 2006; 19: 507 – 511. [3] Simoes-Pires C, Hmicha B, Marston A, Hostettmann K. A TLC bioautographic method for the detection of α- and β-glucosidase inhibitors in plant extracts. Phytochem Anal 2009; 20: 511 – 515.

Research paper thumbnail of Nitric Oxide is Involved in the Mechanism for the Anti-Hypertension Action of Carvedilol

cpfd.cnki.com.cn

【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure thr... more 【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure through a vasorelaxant effect mediated possibly by NO. We have shown that in the rat vas deferens(rvd) NO pathway potentiates the noradrenaline(NE)-release ...

Research paper thumbnail of Regulatory Aspects of Oncologicals: Nanosystems Main Challenges

Advances in Delivery Science and Technology, 2014

The design and development of engineered nanosystems for disease diagnosis, prevention and treatm... more The design and development of engineered nanosystems for disease diagnosis, prevention and treatment has been boosted by significant advances observed in distinct areas. This has been combined in order to attain efficient and safe products. Even if some of those nanoproducts have successfully reached the market, the consensus underlying the nanomedicines-related regulatory requirements has still to be fully acquired by part of the scientific community and thus academia and pharmaceutical companies could be facing considerable obstacles during the research and development life cycle of these medicinal products. However, considerable progress has been made in the last years, reflecting the recognition by Regulatory Authorities of specific features associated to the nanosystems-based medicines. As a consequence, the regulatory environment for those innovative medicinal nanosystems has been increasingly challenged by key issues, which has been an opportunity to provide clearer guidance for their development.

Research paper thumbnail of Current Status and Emerging Opportunities in Replacement of the Lifetime Mouse Cancer Bioassay

Drug Information Journal

The approach to evaluating the carcinogenic potential of pharmaceuticals is a matter of debate an... more The approach to evaluating the carcinogenic potential of pharmaceuticals is a matter of debate and has undergone important changes related to increasing knowledge of the mechanisms of carcinogenesis, accumulated data from carcinogenicity studies, and technological progress. The discussions held during the International Conference of Harmonization (ICH) led to the proposal of a basic principle for carcinogenicity testing: one rodent lifespan study plus an additional short-term study carrying mechanistic insight to the carcinogenicity endpoints. Alternatively, a second lifespan study is acceptable. This approach is in line with the development of alternative models, primarily geneticallymodified mice that are conceived on the basis of known mechanisms of carcinogenesis.

Research paper thumbnail of Shared Learnings on the New EMA First-in-Human and Early Clinical Trial Guideline: Proceedings From a DIAlogue Session at DIA Europe 2018

Therapeutic Innovation & Regulatory Science

Research paper thumbnail of Toxicology and Biodistribution: The Clinical Value of Animal Biodistribution Studies

Molecular Therapy - Methods & Clinical Development

Irrespective of its origin, the development of any innovative product involves the generation of ... more Irrespective of its origin, the development of any innovative product involves the generation of a set of data aimed at informing the human risks posed by its administration, from early-stage (first in human) into late-stage clinical trials and on to wider use after marketing. Understanding of product-related risks helps to determine the safe conditions of human use of the innovative product through the establishment of risk mitigation measures. With such objectives, the nonclinical development program of any innovative product includes three main areas: pharmacodynamics, pharmacokinetics, and toxicology. Pharmacodynamic studies are performed to characterize the mode of action and the primary and secondary targets that may be involved on wanted and unwanted biological effects (primary and secondary pharmacology and safety pharmacology). Pharmacokinetic studies are intended to characterize the profile of absorption, distribution, metabolism, and excretion (ADME) of the developing molecule. Toxicity studies address the toxicological properties in general terms (general toxicity, singledose toxicity, or repeated-dose toxicity studies) and on specific aspects (reproductive toxicity, genotoxicity, carcinogenicity, phototoxicity, immunotoxicity, etc.). 1

Research paper thumbnail of Nonclinical safety evaluation of anticancer medicines for paediatric population (PP): A role for juvenile animal studies?

Research paper thumbnail of Nitric oxide is involved in the mechanism for the antihypertension action of carvedilol

Acta Pharmacologica Sinica, 2006

【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure thr... more 【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure through a vasorelaxant effect mediated possibly by NO. We have shown that in the rat vas deferens(rvd) NO pathway potentiates the noradrenaline(NE)-release ...

Research paper thumbnail of Phytochemical, pre-clinical safety and efficacy evaluation of two Portuguese Asphodelus leaf extracts

Planta Medica, Dec 1, 2022

Research paper thumbnail of Identification of Marker Compounds and In Vitro Toxicity Evaluation of Two Portuguese Asphodelus Leaf Extracts

Molecules, Mar 4, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Bioguided Identification of Active Antimicrobial Compounds from Asphodelus bento-rainhae and Asphodelus macrocarpus Root Tubers

Pharmaceuticals

Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species,... more Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have traditionally been used in Portugal to treat inflammatory and infectious skin disorders. The present study aims to evaluate the in vitro antimicrobial activity of crude 70% and 96% hydroethanolic extracts of both medicinal plants, specifically against multidrug-resistant skin-related pathogens, to identify the involved marker secondary metabolites and also to assess the pre-clinical toxicity of these medicinal plant extracts. Bioguided fractionation of the 70% hydroethanolic extracts of both species using solvents of increasing polarity, namely diethyl ether (DEE: AbR-1, AmR-1), ethyl acetate (AbR-2, AmR-2) and aqueous (AbR-3, AmR-3) fractions, enabled the identification of the DEE fractions as the most active against all the tested Gram-positive microorganisms (MIC: 16 to 1000 µg/mL). Furthermore, phytochemical analyses using TLC...

Research paper thumbnail of Contribution to the Preclinical Safety Assessment of Lannea velutina and Sorindeia juglandifolia Leaves

Plants

Dried leaves of Lannea velutina A. Rich. and Sorindeia juglandifolia (A. Rich.) Planch. ex Oliv. ... more Dried leaves of Lannea velutina A. Rich. and Sorindeia juglandifolia (A. Rich.) Planch. ex Oliv. (family Anacardiaceae) are used in African traditional medicine. Although these medicinal plants have widespread use in the treatment of inflammatory diseases, there is no scientific data concerning their preclinical or clinical safety. This work aimed to investigate the phytochemical properties of the leaves of both species using HPLC-UV/DAD, as well as the in vivo oral repeated-dose toxicity of 70% hydroethanolic leaf extract of S. juglandifolia and the in vitro genotoxicity of 70% hydroethanolic leaf extracts of L. velutina and S. juglandifolia. Clinical signs of toxicity, body weight variations, and changes in food consumption, mortality, and blood biochemical parameters were monitored. Genotoxicity was assessed using the bacterial reverse mutation assay (Ames test) with and without metabolic activation, according to OECD guidelines. The obtained results showed the presence of gallic...

Research paper thumbnail of Monographic Quality Parameters and Genotoxicity Assessment of Asphodelus bento-rainhae and Asphodelus macrocarpus Root Tubers as Herbal Medicines

Plants

Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), an endemic species with relev... more Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), an endemic species with relevant interest due to conservation concerns, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have been traditionally used for culinary and medicinal purposes, mainly associated with skin infection and inflammation. The present study aims to establish the quality control criteria for the proper characterization of dried root tubers of both species as herbal substances, together with their preclinical safety assessments. Botanical identification using macroscopic and microscopic techniques and phytochemical evaluation/quantification of the main classes of marker secondary metabolites, including phenolic compounds (flavonoid, anthraquinone, condensed and hydrolysable tannin) and terpenoids were performed. Additionally, in vitro genotoxicity/mutagenicity was evaluated by Ames test. Evident morphological differences in the development of tubercles (3.5 × 1 cm in AbR and 8.7 × 1.4 cm in AmR)...

Research paper thumbnail of Anti‐inflammatory effect of Rosmarinic acid on a model of carrageenan‐induced paw edema

Research paper thumbnail of Rosmarinic acid reduces multiple organ failure in thermal injury and liver ischemia‐reperfusion injury

Research paper thumbnail of Effect of dietary n-3 PUFA from microalgae on blood, liver, brain, kidney and heart lipids

Research paper thumbnail of Rosmarinic Acid Attenuates Inflammatory-Induced Organ Injury in Thermal Injury and Liver Ischemia-Reperfusion-Injury

Research paper thumbnail of Microalgae a new promising omega 3 fatty acid source

N.M. Bandarra, D. Duarte, R. Pinto, C. Sampayo, M. Ramos, I. Batista, M.L. Nunes, A.P. Batista, A... more N.M. Bandarra, D. Duarte, R. Pinto, C. Sampayo, M. Ramos, I. Batista, M.L. Nunes, A.P. Batista, A. Raymundo, L. Gouveia, B.S. Lima (1) INRB/L-IPIMAR, Av. Brasília 1449-006 Lisboa, Portugal; (2), IMED.UL, Faculdade de Farmácia Universidade de Lisboa, Av das Forcas Armadas 1600 Lisboa, Portugal. (3) Núcleo de Investigação em Engenharia Alimentar e Biotecnologia, Instituto Piaget ISEIT de Almada, Quinta da Arreinela de Cima, 2800-305 Almada, Portugal; (4) Instituto Nacional de Engenharia e Tecnologia Industrial INETI-DER Unidade Biomassa, Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal

Research paper thumbnail of Rat skin physiology is modified by age

Journal Biomedical and Biopharmaceutical Research, 2012

Biomedical and Biopharmaceutical Research J o r n a l d e I n v e s t i g a ç ã o B i o m é d i c... more Biomedical and Biopharmaceutical Research J o r n a l d e I n v e s t i g a ç ã o B i o m é d i c a e B i o f a r m a c ê u t i c a Rat skin physiology is modified by age A Fisiologia da pele de rato é modificada pela idade 1-4

Research paper thumbnail of A Comprehensive Review on the Medicinal Plants from the Genus Asphodelus

Plants, 2018

Plant-based systems continue to play an essential role in healthcare, and their use by different ... more Plant-based systems continue to play an essential role in healthcare, and their use by different cultures has been extensively documented. Asphodelus L. (Asphodelaceae) is a genus of 18 species and of a total of 27 species, sub-species and varieties, distributed along the Mediterranean basin, and has been traditionally used for treating several diseases particularly associated with inflammatory and infectious skin disorders. The present study aimed to provide a general review of the available literature on ethnomedical, phytochemical, and biological data related to the genus Asphodelus as a potential source of new compounds with biological activity. Considering phytochemical studies, 1,8-dihydroxyanthracene derivatives, flavonoids, phenolic acids and triterpenoids were the main classes of compounds identified in roots, leaf and seeds which were correlated with their biological activities as anti-microbial, anti-fungal, anti-parasitic, cytotoxic, anti-inflammatory or antioxidant agents.

Research paper thumbnail of Phenol content, antioxidant and α- and β-glucosidase inhibitory activities of an Anacardium occidentale stem bark Traditional Herbal Preparation

Planta Medica, 2014

Introduction: Anacardium occidentale L., commonly known as cashew tree, has been traditionally us... more Introduction: Anacardium occidentale L., commonly known as cashew tree, has been traditionally used in several countries of Asia, Africa and America, due to its antihyperglycemic properties. Aim of work: To perform comparative studies between Traditional Herbal Preparation (THP) of A. occidentale stem bark red (AOR) and white (AOW) in order to assess their free radical scavenging, α- and β-glucosidase inhibition activities and total phenolic content. Methods: THP total phenol content was determined by the Folin-Ciocalteu method [1], using gallic acid as standard. Simultaneously, the free radical scavenging activity of the THPs was assessed with a 1,1-diphenyl-2-picrylhydrazine (DPPH) assay, using ascorbic acid as reference standard [2]. Moreover bioautographic assays with thin layer chromatography were performed for the detection of α- and β-glucosidase inhibitors [3]. Results: Total phenolic content was found to be 51.3 ± 1.6 and 58.0 ± 0.4 mg of gallic acid equivalent per gram of dried cashew stem bark in AOR and AOW THP, respectively. Concerning the free radical scavenging activity, IC50 value was 180.7 ± 6.7 µg/mL for the AOR THP and 143.8 ± 2.8 µg/mL for the AOW THP. Bioautography showed two chromatogram zones that were identified as α-glucosidase (Rf between 0.55 and 0.68) and β-glucosidase (Rf between 0.63 and 0.87) inhibitors in both THP. Conclusion: Assessed THP proved to be a source of natural antioxidants that may scavenge free radicals. According to data obtained from all experimental assays, AOW THP has higher antioxidant activity and total phenolic content than AOR THP. Moreover, extracts from both types of A. occidentale promoted inhibition of α- and β-glucosidase. Acknowledgements: This work was supported by grant Pest-OE/SAU/UI4013/2011 from Fundacao para a Ciencia e Tecnologia, Lisbon, Portugal. Keywords: Cashew stem bark, Traditional Herbal Preparation References: [1] Scalbert A, Monties B, Jannin G. Tannins in wood: comparison of different estimation methods. J Agricult Food Chem 1989; 37(5): 1324 – 1329. [2] Silva T, Camara C, Lins A, Barbosa-Filho J, Silva E, Freitas B, Santos F. Chemical composition and free radical scavenging activity of pollen loads from stingless bee Melipona subnitida Ducke. J Food Comp Anal 2006; 19: 507 – 511. [3] Simoes-Pires C, Hmicha B, Marston A, Hostettmann K. A TLC bioautographic method for the detection of α- and β-glucosidase inhibitors in plant extracts. Phytochem Anal 2009; 20: 511 – 515.

Research paper thumbnail of Nitric Oxide is Involved in the Mechanism for the Anti-Hypertension Action of Carvedilol

cpfd.cnki.com.cn

【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure thr... more 【摘要】:正 Carvedilol(Carv) is a unselective β-adrenoceptor antagonist,that lowers blood pressure through a vasorelaxant effect mediated possibly by NO. We have shown that in the rat vas deferens(rvd) NO pathway potentiates the noradrenaline(NE)-release ...

Research paper thumbnail of Regulatory Aspects of Oncologicals: Nanosystems Main Challenges

Advances in Delivery Science and Technology, 2014

The design and development of engineered nanosystems for disease diagnosis, prevention and treatm... more The design and development of engineered nanosystems for disease diagnosis, prevention and treatment has been boosted by significant advances observed in distinct areas. This has been combined in order to attain efficient and safe products. Even if some of those nanoproducts have successfully reached the market, the consensus underlying the nanomedicines-related regulatory requirements has still to be fully acquired by part of the scientific community and thus academia and pharmaceutical companies could be facing considerable obstacles during the research and development life cycle of these medicinal products. However, considerable progress has been made in the last years, reflecting the recognition by Regulatory Authorities of specific features associated to the nanosystems-based medicines. As a consequence, the regulatory environment for those innovative medicinal nanosystems has been increasingly challenged by key issues, which has been an opportunity to provide clearer guidance for their development.

Research paper thumbnail of Current Status and Emerging Opportunities in Replacement of the Lifetime Mouse Cancer Bioassay

Drug Information Journal

The approach to evaluating the carcinogenic potential of pharmaceuticals is a matter of debate an... more The approach to evaluating the carcinogenic potential of pharmaceuticals is a matter of debate and has undergone important changes related to increasing knowledge of the mechanisms of carcinogenesis, accumulated data from carcinogenicity studies, and technological progress. The discussions held during the International Conference of Harmonization (ICH) led to the proposal of a basic principle for carcinogenicity testing: one rodent lifespan study plus an additional short-term study carrying mechanistic insight to the carcinogenicity endpoints. Alternatively, a second lifespan study is acceptable. This approach is in line with the development of alternative models, primarily geneticallymodified mice that are conceived on the basis of known mechanisms of carcinogenesis.

Research paper thumbnail of Shared Learnings on the New EMA First-in-Human and Early Clinical Trial Guideline: Proceedings From a DIAlogue Session at DIA Europe 2018

Therapeutic Innovation & Regulatory Science

Research paper thumbnail of Toxicology and Biodistribution: The Clinical Value of Animal Biodistribution Studies

Molecular Therapy - Methods & Clinical Development

Irrespective of its origin, the development of any innovative product involves the generation of ... more Irrespective of its origin, the development of any innovative product involves the generation of a set of data aimed at informing the human risks posed by its administration, from early-stage (first in human) into late-stage clinical trials and on to wider use after marketing. Understanding of product-related risks helps to determine the safe conditions of human use of the innovative product through the establishment of risk mitigation measures. With such objectives, the nonclinical development program of any innovative product includes three main areas: pharmacodynamics, pharmacokinetics, and toxicology. Pharmacodynamic studies are performed to characterize the mode of action and the primary and secondary targets that may be involved on wanted and unwanted biological effects (primary and secondary pharmacology and safety pharmacology). Pharmacokinetic studies are intended to characterize the profile of absorption, distribution, metabolism, and excretion (ADME) of the developing molecule. Toxicity studies address the toxicological properties in general terms (general toxicity, singledose toxicity, or repeated-dose toxicity studies) and on specific aspects (reproductive toxicity, genotoxicity, carcinogenicity, phototoxicity, immunotoxicity, etc.). 1

Research paper thumbnail of Nonclinical safety evaluation of anticancer medicines for paediatric population (PP): A role for juvenile animal studies?