The incidence and progression of disorders associated with an unbalanced immune response has amon... more The incidence and progression of disorders associated with an unbalanced immune response has among many factors the gender as a contributory factor. The aims of this work were to evaluate the effects of orchiectomy and the immune response during the experimental Trypanosoma cruzi infection. Young adult, male Calomys callous were i.p. inoculated with 1 Â 10 5 blood trypomastigotes of the CM strain of T. cruzi and divided in groups: Control, Sham and Castrated. Castrated group displayed significantly lower values for prostate and seminal vesicle weights indicating a drastic drop of testosterone plasmatic levels. Orchiectomized animals also displayed lesser number of blood parasites, enhanced lytic antibody percentage, splenocyte proliferation and NO concentration when compared to its sham and control counterparts, indicating that steroid gonadal ablation actually influences immune response triggering a more efficient cellular and humoral response which led animals to become more resistant against T. cruzi infection.
Trying to surpass host defenses, fungal infections alter the immune response. Components from non... more Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1β, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.
Trastuzumab administered in combination with various chemotherapy regimens has led to outstanding... more Trastuzumab administered in combination with various chemotherapy regimens has led to outstanding improvements in both disease-free survival and overall survival. So far, thousands of patients have been treated in this way which has proven to be reasonably safe, with cardiac events being the predominant recognisable toxicity requiring surveillance. Notwithstanding the large cumulative experience of the oncology community in treating early HER2/neu-positive breast cancer with trastuzumab, some uncertainties remain, with key issues being the ideal time of chemotherapy administration and the optimal duration of trastuzumab therapy. This paper discusses these issues in the light of the recent updates of some of the pivotal clinical trials in the adjuvant context.
Background: Information is vital to cancer patients. Physician-patient communication in oncology ... more Background: Information is vital to cancer patients. Physician-patient communication in oncology presents specific challenges. The aim of this study was to evaluate self-reported information of cancer patients in ambulatory care at a comprehensive cancer centre and examine its possible association with patients' demographic and clinical characteristics.
Current topics in microbiology and immunology, 2015
The existence and significance of endogenous cytosolic and nuclear mono-ADP-ribosylation has been... more The existence and significance of endogenous cytosolic and nuclear mono-ADP-ribosylation has been a matter of debate. Today, evidence suggests that the human enzymes that catalyze the reaction have been rounded up. Moreover, substrate proteins and specific functions for mono-ADP-ribosyltransferases are beginning to be defined. Reader domains that specifically recognize mono-ADP-ribosylated target proteins and erasers that remove the mono-ADP-ribosyl mark have been identified. Here, we review the contribution of crystal structures to our understanding of the putative mono-ADP-ribosyltransferases with Diphtheria toxin and ARTD1/PARP1 homology.
Inter-hemispheric modulation has been extensively studied, as it is critical for human behavior a... more Inter-hemispheric modulation has been extensively studied, as it is critical for human behavior and could be involved in the development of neuropsychiatric disorders, such as major depression, epilepsy and stroke. Malnutrition early in life can alter brain processes such as inter-hemispheric modulation and these alterations can persist into adulthood. Here, we used cortical spreading depression (CSD) as a neurophysiological parameter to investigate inter-hemispheric modulation in 19 well-nourished and 18 early-malnourished male adult rats. CSD was evoked on the right frontal region and monitored at two parietal points on the same hemisphere. After a 2 h baseline recording, Wbers projecting from the left to the right hemisphere via the corpus callosum were cut with a longitudinal lesion in the contralateral cortex and recording continued for two more hours. The results show that (1) baseline CSD propagation velocities were higher in the malnourished rats, as compared to the respective well-nourished controls; (2) postlesion velocities increased in both nutritional groups, as compared with the baseline values; (3) this CSD increase persisted 3-7 days after lesion, suggesting a lasting eVect and (4) in the malnourished group the post-lesion CSD enhancement was of smaller amplitude. Furthermore, a midline lesion (callosotomy) in eight well-nourished rats similarly facilitated CSD, suggesting the involvement of callosal Wbers on this eVect. No diVerences were found in sham-operated rats (21 well-nourished and 21 malnourished), as well as in a superWcial (1 mm deep) contralateral lesion group (8 well-nourished). Results support the hypothesis of a lasting inhibitory contralateral inXuence on CSD propagation, which is attenuated, but not abolished, by early malnutrition.
Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines ca... more Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines can cause permanent damage, anti-HER2 agents may cause transitory and reversible cardiac dysfunction and others, such as those used in endocrine therapy, primarily disturb lipid metabolism. Considering the seriousness of these complications, trials are now being conducted to address cardiotoxicity associated with new drugs; however, to fully understand their toxicity profiles, longer follow-up is needed. In this review, we compile the information available about cardiac toxicity related to well-established systemic breast cancer treatments, as well as newer drugs, including antiangiogenics, mTOR inhibitors and novel anti-HER2 agents. We also describe current and next generation cardiac biomarkers and functional tests that can optimize treatment and reduce and prevent the incidence of treatment-related cardiotoxicity.
JBIC Journal of Biological Inorganic Chemistry, 2014
Superoxide reductases (SORs) are the most recently identified superoxide detoxification systems, ... more Superoxide reductases (SORs) are the most recently identified superoxide detoxification systems, being found in microorganisms from the three domains of life. These enzymes are characterized by a catalytic mononuclear iron site, with one cysteine and four histidine ligands of the ferrous active form. A lysine residue in the -EKHVP- motif, located close to the active site, has been considered to be essential for the enzyme function, by contributing to the positive surface patch that attracts the superoxide anion and by controlling the chemistry of the catalytic mechanism through a hydrogen bond network. However, we show here that this residue is substituted by non-equivalent amino acids in several putative SORs from Archaea and unicellular Eukarya. In this work, we focus on mechanistic and spectroscopic studies of one of these less common enzymes, the SOR from the hyperthermophilic Crenarchaeon Ignicoccus hospitalis. We employ pulse radiolysis fast kinetics and spectroscopic approaches to study the wild-type enzyme (-E23T24HVP-), and two mutants, T24K and E23A, the later mimicking enzymes lacking both the lysine and glutamate (a ferric ion ligand) of the motif. The efficiency of the wild-type protein and mutants in reducing superoxide is comparable to other SORs, revealing the robustness of these enzymes to single mutations.
EuroSCORE e os pacientes submetidos a revascularização do miocárdio na Santa Casa de São Paulo Ar... more EuroSCORE e os pacientes submetidos a revascularização do miocárdio na Santa Casa de São Paulo Artigo recebido em 28 de novembro de 2007 Artigo aprovado em 18 de fevereiro de 2008 Resumo Objetivo: Avaliar o perfil atual do paciente submetido a revascularização do miocárdio na Disciplina de Cirurgia Cardíaca da Faculdade de Ciências Médicas da Santa Casa de São Paulo, verificar o risco de mortalidade esperada neste grupo, por meio da aplicação do Sistema Europeu de Risco em Operações Cardíacas (EuroSCORE), e confrontá-lo com a mortalidade observada. Métodos: Analisamos 100 pacientes consecutivos submetidos a revascularização do miocárdio, de maio de 2005 a novembro de 2006. Identificamos os fatores predisponentes à coronariopatia e analisamos os critérios de risco de mortalidade pelo EuroSCORE. Comparamos as taxas de mortalidade esperadas com as observadas na amostra.
Sexuality and sexual functioning is a cardinal domain of health-related quality of life in breast... more Sexuality and sexual functioning is a cardinal domain of health-related quality of life in breast cancer patients, namely in the younger population. Young women below 40 years of age go through a time in their lives where sexual self-identity has recently matured, their professional obligations are demanding and they bear interpersonal and childbearing expectations, all of which can suffer a devastating turnaround with cancer diagnosis and its physical and psychological aftermath. Although these women's sexuality and directed interventions have remained largely unaddressed so far, concepts are evolving and treatment options are becoming diversified, chiefly on the field of non-hormonal pharmacological therapy of sexual dysfunction. This review will examine the definitions of female sexual dysfunction, the etiology of the disorders in young breast cancer patients, the assessment methods, the non-pharmacological and pharmacological treatment options and the challenges that lie ahead.
Microemulsions (MEs) were designed by an innovative rational development, characterized, and used... more Microemulsions (MEs) were designed by an innovative rational development, characterized, and used to load up to 20 mM of Tamoxifen citrate (TMX). They were made with acceptable and well-characterized excipients for all the routes of administration. Some of their properties, such as nanometric mean size and long stability shelf life, make them interesting drug delivery systems. The results obtained after the in vitro inhibition of estradiol-induced proliferation in MCF-7 breast cancer cells demonstrated a significant effect in cell growth. A decreasing of at least 90% in viable cells was shown after the incubation with MEs containing 20 mM of TMX. Besides, two compositions which loaded 10 mM of drug showed a cytotoxic effect higher than 70%. These results encourage the evaluation of alternative protocols for this drug administration, not only for estrogen receptor (ER) positive tumors, but also for ER negative.
Objective: (i) To study the functioning patterns of young children with disabilities compared wit... more Objective: (i) To study the functioning patterns of young children with disabilities compared with typically developing children, using a new ICF-CY based tool -the Matrix for Assessment of Activities and Participation; (ii) study the factors that predict these functioning patterns. Methods: The MAAP tool was administered to three groups of children: (i) with autism, (ii) with other types of disabilities and (iii) typically developing. Results: Cluster analysis showed that children group according to the severity of their functioning profile and not according to the diagnostic category in which they were classified. Multiple regression analysis showed that a model comprising the environmental factors and the level of engagement in different routines of the child is a good predictor of these children's functioning patterns. Conclusion: These results support a functional approach to disability instead of the traditional medical model approach, underlining the role of engagement and environment in determining functioning.
Piper peltatum L. is used for the treatment of inflammation, malaria, and other ailments. 4-Nerol... more Piper peltatum L. is used for the treatment of inflammation, malaria, and other ailments. 4-Nerolidylcatechol (4-NC) is a valuable natural product that has important anti-inflammatory, antimalarial, and antioxidant properties. 4-NC is a component of P. peltatum and P. umbellatum extracts, which are used in cosmetics. The aim of this work was to evaluate the production of plant biomass and the production of 4-NC in roots of cultivated P. peltatum over a full life cycle. Seedlings were produced in a greenhouse and then transplanted. The weight of dry plant parts (leaves, stems, roots, and inflorescences); numbers of stems, leaves, and inflorescences; and the leaf-to-stem ratio were evaluated at intervals of 60 days after transplanting (DAT). Extracts were prepared using 1 : 1 ethanol-chloroform and an ultrasound bath. Roots, leaves, and inflorescences contained 4-NC according to TLC photodensitometry analysis. Quantification of 4-NC in root extracts was performed using HPLC-DAD analysis. Per-hectare production of 4-NC by roots was estimated based on quantitative HPLC analysis and biomass data. Optimal per-hectare yields of 4-NC were obtained by harvesting roots between 350 and 400 DAT. In this period, the average yield was 27 kg 4-NC per hectare. Importantly, at the time of maximal overall production of root biomass (470 DAT), there was a decrease in the production of 4-NC (23.8 kg/ha), probably due to the onset of senescence.
Human colon carcinoma Human nervous system cancer Melanoma Human myeloblastic leukemia Semi-synth... more Human colon carcinoma Human nervous system cancer Melanoma Human myeloblastic leukemia Semi-synthetic 4-nerolidylcatechol derivatives a b s t r a c t 4-Nerolidylcatechol (1) was isolated from cultivated Pothomorphe peltata root on a multigram scale using straight-forward solvent extraction-column chromatography. New semi-synthetic derivatives of 1 were prepared and tested in vitro against multidrug-resistant Plasmodium falciparum K1 strain. Mono-O-methyl, mono-O-benzyl, O,O-dibenzyl and O,O-dibenzoyl derivatives 2-8 exhibited IC 50 in the 0.67-22.52 mM range. Mono-O-methyl ethers 6 and 7 inhibited the in vitro growth of human tumor cell lines HCT-8 (colon carcinoma), SF-295 (central nervous system), LH-60 (human myeloblastic leukemia) and MDA/MB-435 (melanoma). In general, derivatives 2-8 are more stable to light, air and pH at ambient temperatures than their labile, natural precursor 1. These derivatives provide leads for the development of a novel class of antimalarial drugs with enhanced chemical and pharmacological properties.
The incidence and progression of disorders associated with an unbalanced immune response has amon... more The incidence and progression of disorders associated with an unbalanced immune response has among many factors the gender as a contributory factor. The aims of this work were to evaluate the effects of orchiectomy and the immune response during the experimental Trypanosoma cruzi infection. Young adult, male Calomys callous were i.p. inoculated with 1 Â 10 5 blood trypomastigotes of the CM strain of T. cruzi and divided in groups: Control, Sham and Castrated. Castrated group displayed significantly lower values for prostate and seminal vesicle weights indicating a drastic drop of testosterone plasmatic levels. Orchiectomized animals also displayed lesser number of blood parasites, enhanced lytic antibody percentage, splenocyte proliferation and NO concentration when compared to its sham and control counterparts, indicating that steroid gonadal ablation actually influences immune response triggering a more efficient cellular and humoral response which led animals to become more resistant against T. cruzi infection.
Trying to surpass host defenses, fungal infections alter the immune response. Components from non... more Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1β, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.
Trastuzumab administered in combination with various chemotherapy regimens has led to outstanding... more Trastuzumab administered in combination with various chemotherapy regimens has led to outstanding improvements in both disease-free survival and overall survival. So far, thousands of patients have been treated in this way which has proven to be reasonably safe, with cardiac events being the predominant recognisable toxicity requiring surveillance. Notwithstanding the large cumulative experience of the oncology community in treating early HER2/neu-positive breast cancer with trastuzumab, some uncertainties remain, with key issues being the ideal time of chemotherapy administration and the optimal duration of trastuzumab therapy. This paper discusses these issues in the light of the recent updates of some of the pivotal clinical trials in the adjuvant context.
Background: Information is vital to cancer patients. Physician-patient communication in oncology ... more Background: Information is vital to cancer patients. Physician-patient communication in oncology presents specific challenges. The aim of this study was to evaluate self-reported information of cancer patients in ambulatory care at a comprehensive cancer centre and examine its possible association with patients' demographic and clinical characteristics.
Current topics in microbiology and immunology, 2015
The existence and significance of endogenous cytosolic and nuclear mono-ADP-ribosylation has been... more The existence and significance of endogenous cytosolic and nuclear mono-ADP-ribosylation has been a matter of debate. Today, evidence suggests that the human enzymes that catalyze the reaction have been rounded up. Moreover, substrate proteins and specific functions for mono-ADP-ribosyltransferases are beginning to be defined. Reader domains that specifically recognize mono-ADP-ribosylated target proteins and erasers that remove the mono-ADP-ribosyl mark have been identified. Here, we review the contribution of crystal structures to our understanding of the putative mono-ADP-ribosyltransferases with Diphtheria toxin and ARTD1/PARP1 homology.
Inter-hemispheric modulation has been extensively studied, as it is critical for human behavior a... more Inter-hemispheric modulation has been extensively studied, as it is critical for human behavior and could be involved in the development of neuropsychiatric disorders, such as major depression, epilepsy and stroke. Malnutrition early in life can alter brain processes such as inter-hemispheric modulation and these alterations can persist into adulthood. Here, we used cortical spreading depression (CSD) as a neurophysiological parameter to investigate inter-hemispheric modulation in 19 well-nourished and 18 early-malnourished male adult rats. CSD was evoked on the right frontal region and monitored at two parietal points on the same hemisphere. After a 2 h baseline recording, Wbers projecting from the left to the right hemisphere via the corpus callosum were cut with a longitudinal lesion in the contralateral cortex and recording continued for two more hours. The results show that (1) baseline CSD propagation velocities were higher in the malnourished rats, as compared to the respective well-nourished controls; (2) postlesion velocities increased in both nutritional groups, as compared with the baseline values; (3) this CSD increase persisted 3-7 days after lesion, suggesting a lasting eVect and (4) in the malnourished group the post-lesion CSD enhancement was of smaller amplitude. Furthermore, a midline lesion (callosotomy) in eight well-nourished rats similarly facilitated CSD, suggesting the involvement of callosal Wbers on this eVect. No diVerences were found in sham-operated rats (21 well-nourished and 21 malnourished), as well as in a superWcial (1 mm deep) contralateral lesion group (8 well-nourished). Results support the hypothesis of a lasting inhibitory contralateral inXuence on CSD propagation, which is attenuated, but not abolished, by early malnutrition.
Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines ca... more Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines can cause permanent damage, anti-HER2 agents may cause transitory and reversible cardiac dysfunction and others, such as those used in endocrine therapy, primarily disturb lipid metabolism. Considering the seriousness of these complications, trials are now being conducted to address cardiotoxicity associated with new drugs; however, to fully understand their toxicity profiles, longer follow-up is needed. In this review, we compile the information available about cardiac toxicity related to well-established systemic breast cancer treatments, as well as newer drugs, including antiangiogenics, mTOR inhibitors and novel anti-HER2 agents. We also describe current and next generation cardiac biomarkers and functional tests that can optimize treatment and reduce and prevent the incidence of treatment-related cardiotoxicity.
JBIC Journal of Biological Inorganic Chemistry, 2014
Superoxide reductases (SORs) are the most recently identified superoxide detoxification systems, ... more Superoxide reductases (SORs) are the most recently identified superoxide detoxification systems, being found in microorganisms from the three domains of life. These enzymes are characterized by a catalytic mononuclear iron site, with one cysteine and four histidine ligands of the ferrous active form. A lysine residue in the -EKHVP- motif, located close to the active site, has been considered to be essential for the enzyme function, by contributing to the positive surface patch that attracts the superoxide anion and by controlling the chemistry of the catalytic mechanism through a hydrogen bond network. However, we show here that this residue is substituted by non-equivalent amino acids in several putative SORs from Archaea and unicellular Eukarya. In this work, we focus on mechanistic and spectroscopic studies of one of these less common enzymes, the SOR from the hyperthermophilic Crenarchaeon Ignicoccus hospitalis. We employ pulse radiolysis fast kinetics and spectroscopic approaches to study the wild-type enzyme (-E23T24HVP-), and two mutants, T24K and E23A, the later mimicking enzymes lacking both the lysine and glutamate (a ferric ion ligand) of the motif. The efficiency of the wild-type protein and mutants in reducing superoxide is comparable to other SORs, revealing the robustness of these enzymes to single mutations.
EuroSCORE e os pacientes submetidos a revascularização do miocárdio na Santa Casa de São Paulo Ar... more EuroSCORE e os pacientes submetidos a revascularização do miocárdio na Santa Casa de São Paulo Artigo recebido em 28 de novembro de 2007 Artigo aprovado em 18 de fevereiro de 2008 Resumo Objetivo: Avaliar o perfil atual do paciente submetido a revascularização do miocárdio na Disciplina de Cirurgia Cardíaca da Faculdade de Ciências Médicas da Santa Casa de São Paulo, verificar o risco de mortalidade esperada neste grupo, por meio da aplicação do Sistema Europeu de Risco em Operações Cardíacas (EuroSCORE), e confrontá-lo com a mortalidade observada. Métodos: Analisamos 100 pacientes consecutivos submetidos a revascularização do miocárdio, de maio de 2005 a novembro de 2006. Identificamos os fatores predisponentes à coronariopatia e analisamos os critérios de risco de mortalidade pelo EuroSCORE. Comparamos as taxas de mortalidade esperadas com as observadas na amostra.
Sexuality and sexual functioning is a cardinal domain of health-related quality of life in breast... more Sexuality and sexual functioning is a cardinal domain of health-related quality of life in breast cancer patients, namely in the younger population. Young women below 40 years of age go through a time in their lives where sexual self-identity has recently matured, their professional obligations are demanding and they bear interpersonal and childbearing expectations, all of which can suffer a devastating turnaround with cancer diagnosis and its physical and psychological aftermath. Although these women's sexuality and directed interventions have remained largely unaddressed so far, concepts are evolving and treatment options are becoming diversified, chiefly on the field of non-hormonal pharmacological therapy of sexual dysfunction. This review will examine the definitions of female sexual dysfunction, the etiology of the disorders in young breast cancer patients, the assessment methods, the non-pharmacological and pharmacological treatment options and the challenges that lie ahead.
Microemulsions (MEs) were designed by an innovative rational development, characterized, and used... more Microemulsions (MEs) were designed by an innovative rational development, characterized, and used to load up to 20 mM of Tamoxifen citrate (TMX). They were made with acceptable and well-characterized excipients for all the routes of administration. Some of their properties, such as nanometric mean size and long stability shelf life, make them interesting drug delivery systems. The results obtained after the in vitro inhibition of estradiol-induced proliferation in MCF-7 breast cancer cells demonstrated a significant effect in cell growth. A decreasing of at least 90% in viable cells was shown after the incubation with MEs containing 20 mM of TMX. Besides, two compositions which loaded 10 mM of drug showed a cytotoxic effect higher than 70%. These results encourage the evaluation of alternative protocols for this drug administration, not only for estrogen receptor (ER) positive tumors, but also for ER negative.
Objective: (i) To study the functioning patterns of young children with disabilities compared wit... more Objective: (i) To study the functioning patterns of young children with disabilities compared with typically developing children, using a new ICF-CY based tool -the Matrix for Assessment of Activities and Participation; (ii) study the factors that predict these functioning patterns. Methods: The MAAP tool was administered to three groups of children: (i) with autism, (ii) with other types of disabilities and (iii) typically developing. Results: Cluster analysis showed that children group according to the severity of their functioning profile and not according to the diagnostic category in which they were classified. Multiple regression analysis showed that a model comprising the environmental factors and the level of engagement in different routines of the child is a good predictor of these children's functioning patterns. Conclusion: These results support a functional approach to disability instead of the traditional medical model approach, underlining the role of engagement and environment in determining functioning.
Piper peltatum L. is used for the treatment of inflammation, malaria, and other ailments. 4-Nerol... more Piper peltatum L. is used for the treatment of inflammation, malaria, and other ailments. 4-Nerolidylcatechol (4-NC) is a valuable natural product that has important anti-inflammatory, antimalarial, and antioxidant properties. 4-NC is a component of P. peltatum and P. umbellatum extracts, which are used in cosmetics. The aim of this work was to evaluate the production of plant biomass and the production of 4-NC in roots of cultivated P. peltatum over a full life cycle. Seedlings were produced in a greenhouse and then transplanted. The weight of dry plant parts (leaves, stems, roots, and inflorescences); numbers of stems, leaves, and inflorescences; and the leaf-to-stem ratio were evaluated at intervals of 60 days after transplanting (DAT). Extracts were prepared using 1 : 1 ethanol-chloroform and an ultrasound bath. Roots, leaves, and inflorescences contained 4-NC according to TLC photodensitometry analysis. Quantification of 4-NC in root extracts was performed using HPLC-DAD analysis. Per-hectare production of 4-NC by roots was estimated based on quantitative HPLC analysis and biomass data. Optimal per-hectare yields of 4-NC were obtained by harvesting roots between 350 and 400 DAT. In this period, the average yield was 27 kg 4-NC per hectare. Importantly, at the time of maximal overall production of root biomass (470 DAT), there was a decrease in the production of 4-NC (23.8 kg/ha), probably due to the onset of senescence.
Human colon carcinoma Human nervous system cancer Melanoma Human myeloblastic leukemia Semi-synth... more Human colon carcinoma Human nervous system cancer Melanoma Human myeloblastic leukemia Semi-synthetic 4-nerolidylcatechol derivatives a b s t r a c t 4-Nerolidylcatechol (1) was isolated from cultivated Pothomorphe peltata root on a multigram scale using straight-forward solvent extraction-column chromatography. New semi-synthetic derivatives of 1 were prepared and tested in vitro against multidrug-resistant Plasmodium falciparum K1 strain. Mono-O-methyl, mono-O-benzyl, O,O-dibenzyl and O,O-dibenzoyl derivatives 2-8 exhibited IC 50 in the 0.67-22.52 mM range. Mono-O-methyl ethers 6 and 7 inhibited the in vitro growth of human tumor cell lines HCT-8 (colon carcinoma), SF-295 (central nervous system), LH-60 (human myeloblastic leukemia) and MDA/MB-435 (melanoma). In general, derivatives 2-8 are more stable to light, air and pH at ambient temperatures than their labile, natural precursor 1. These derivatives provide leads for the development of a novel class of antimalarial drugs with enhanced chemical and pharmacological properties.
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Papers by Ana Pinto