<p><b>A–B</b>. Percentage increase in left ventricular ejection fraction and fr... more <p><b>A–B</b>. Percentage increase in left ventricular ejection fraction and fractional shortening measured by echocardiography. Systolic tension (<b>C</b>) and cardiomyocyte shortening (<b>D</b>) measurements were performed in WT and α<sub>2A</sub>/α<sub>2C</sub>-KO mice treated or not with pyridostigmine. Cholinesterase inhibition therapy restored cardiac function and and cellular contractile function of α<sub>2A</sub>/α<sub>2C–</sub>KO mice to control levels. *p<0.05 when compared to WT and α<sub>2A</sub>/α<sub>2C–</sub>KO/PYR.</p
Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of th... more Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of the fetus' full growth potential and occurs in a natural and severe manner in pigs as a result of placental insufficiency. Reduced skeletal muscle mass in the fetus with IUGR persists into adulthood and may contribute to increased metabolic disease risk. To investigate skeletal muscle postnatal development, histomorphometrical patterns of the semitendinosus muscle, myosin heavy chain (MyHC; embryonic I, IIA, IIB and IIX isoforms) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100 days old), hypertrophy (100–150 days old), and postnatal development (newborn to 150 days old) were evaluated in female pigs with IUGR and normal birth weight (NW) female littermates. NW females presented higher body weights compared to their IUGR counterparts at all ages evaluated (P < 0.05). Moreover, growth restriction in utero affected the semitendinosus muscle weight, muscle fiber diameter, and muscle cross‐sectional area, which were smaller in IUGR pigs at birth (P < 0.05). Notwithstanding the effects on muscle morphology, IUGR also affected muscle fiber composition, as the percentage of MyHC‐I myofibers was higher at birth (P < 0.05), and, in 150‐day‐old gilts, a lower percentage of MyHC‐IIX isoform (P < 0.05) and the presence of embryonic MyHC isoform were also observed. Regarding the pattern of gene expression in both the postnatal myogenesis and postnatal development periods, IUGR led to the downregulation of myogenic factors, which delayed skeletal muscle myogenesis (PAX7, MYOD, MYOG, MYF5 and DES). Altogether, growth restriction in utero affects muscle fiber number and size at birth and muscle fiber composition through the downregulation of myogenic factors, which determines the individual´s postnatal growth rate. This fact, associated with delayed myofiber development in growth‐restricted animals, may affect meat quality characteristics in animal production. Hence, knowledge of the morphofunctional phenotype of the skeletal muscle throughout postnatal development in individuals with IUGR, and the mechanism that governs it, may provide a better understanding of the mechanisms that limit postnatal muscle growth, and help the establishment of potential strategies to improve muscle development and prevent the onset of later‐life metabolic diseases.
Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of th... more Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of the fetus full growth potential and occurs in a natural and severe manner in pigs. Knowledge on skeletal muscle morphofunctional phenotype and its molecular regulation in IUGR pigs is important to understand postnatal muscle development and may help the establishment of therapies to improve skeletal muscle growth in those individuals. To investigate the impairment of skeletal muscle postnatal development due to IUGR, we evaluated the histomorphometrical pattern of the semitendinosus muscle, the Myosin Heavy Chain (embryonic, I, IIa, IIb and IIx MyHC) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100 days of age), postnatal development (newborn to 150 days of age), and hypertrophy (100 days to 150 days of age), comparing IUGR and normal birth weight (NW) pigs. Growth restr...
Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients wit... more Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC. Forty-nine patients with ChC (50 ± 7 years, New York Heart Association "NYHA" I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression. After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval ...
Chagas disease is an infection caused by the parasite Trypanosoma cruzi that affects millions of ... more Chagas disease is an infection caused by the parasite Trypanosoma cruzi that affects millions of people worldwide and is endemic in Latin America. Megacolon is the most frequent complication of the digestive chronic form and happens due to lesions of the enteric nervous system. The neuronal lesions seem to initiate in the acute phase and persist during the chronic phase, albeit the mechanisms involved in this process are still debated. Among the cells of the immune system possibly involved in this pathological process is the mast cell (MC) due to its well-known role in the bi-directional communication between the immune and nervous systems. Using ultrastructural analysis, we found an increased number of degranulated MCs in close proximity to nerve fibers in infected patients when compared with uninfected controls. We also immunostained MCs for the two pro-inflammatory molecules tryptase and chymase, the first being also important in neuronal death. The number of MCs immunostained fo...
PnPP-19 is a 19-amino-acid synthetic peptide previously described as a novel drug for the treatme... more PnPP-19 is a 19-amino-acid synthetic peptide previously described as a novel drug for the treatment of erectile dysfunction. The aim of this work was to evaluate the physicochemical properties of cationic transfersomes containing PnPP-19 and the skin permeation of free PnPP-19 and PnPP-19-loaded transfersomes. Three different liposomal preparation methods were evaluated. Cationic transfersomes contained egg phosphatidyl choline: stearylamine (9:1 w/w) and Tween 20 (84.6:15.4 lipid:Tween, w/w). Lipid concentration varied from 20 to 40 mM. We evaluated the entrapment percentage, mean diameter, zeta potential and stability at 4 oC of the formulations. The skin permeation assays were performed with abdominal human skin using Franz diffusion cell with 3 cm2 diffusion area at 32 oC and a fluorescent derivative of the peptide, containing 5-TAMRA, bound to PnPP-19 C-terminal region, where an extra lysine was inserted. Our results showed variable entrapment efficiencies, from 6% to 30%, depe...
Although cardiac dysautonomia is a distinctive feature of Chagas disease, its clinical and functi... more Although cardiac dysautonomia is a distinctive feature of Chagas disease, its clinical and functional significance is still being speculated. Neurotrophic factors are potentially involved; however, studies of their effect in this infection are rare. Ultrastructural abnormalities in autonomic varicosities, levels of both nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF), as well as the expression of their receptors, were analysed in the heart of a rat model of Trypanosoma infection. Predominantly, at the early stage of the infection, cardiac autonomic varicosities displayed several signs of degeneration parallel to the elevation of cardiac levels of NGF, as well as expression of the receptors TrkA and p75NTR. For BDNF and TrkB, the changes were less conspicuous. Data obtained here can contribute to further clarify the factors related to the autonomic nervous system's adaptive changes that could determine the evolution of different clinical forms of Chagas di...
Background Aerobic exercise, even for short durations, may promote an increase in serum concentra... more Background Aerobic exercise, even for short durations, may promote an increase in serum concentrations of brain-derived neurotrophic factor (BDNF). However, it is necessary to determine the optimal exercise types and intensities to increase BDNF levels. Objectives This aim of this study was investigate the effects of mild and moderate intensity acute aerobic exercise on serum BDNF levels in patients in the chronic post-stroke phase. Methods The participants answered a socio-demographic questionnaire, cognitive assessment (Mini Mental State Examination), assessment of depressive symptoms (Hamilton Depression Scale), fatigue (Fatigue Severity Scale) and functional capacity (6-minute walk test). Blood samples were collected before and after each session. The measurement of the concentration of BDNF was performed using the enzyme-linked immunosorbent assay . Patients were asked to walk for 30-min in the target training zone (mild intensity, 50-63% of maximum heart rate, and moderate int...
The etiology of trigeminal neuropathic pain is not clear, but there is evidence that demyelinatio... more The etiology of trigeminal neuropathic pain is not clear, but there is evidence that demyelination, expression of cytokines, neuropeptides, and neurotrophic factors are crucial contributors. In order to elucidate mechanisms underlying trigeminal neuropathic pain, we evaluated the time course of morphological changes in myelinated and unmyelinated trigeminal nerve fibers, expression of cytokine IL-1β, neuropeptide substance P (SP), nerve growth factor (NGF), and glial derived neurotrophic factor (GDNF) in peripheral and ganglion tissues, using a rat model of trigeminal neuropathic pain. Chronic constriction injury (CCI) of the infraorbital nerve (IoN), or a sham surgery, was performed. Mechanical allodynia was evaluated from day 3 to day 15 post-surgery. Trigeminal nerves were divided into 2 sections - distal to CCI and ganglion - for morphological analyses, immunohistochemistry (IL-1β, SP), and protein quantification by ELISA (NGF, GDNF). At early postoperative time points, decrease...
<p><b>A–B</b>. Percentage increase in left ventricular ejection fraction and fr... more <p><b>A–B</b>. Percentage increase in left ventricular ejection fraction and fractional shortening measured by echocardiography. Systolic tension (<b>C</b>) and cardiomyocyte shortening (<b>D</b>) measurements were performed in WT and α<sub>2A</sub>/α<sub>2C</sub>-KO mice treated or not with pyridostigmine. Cholinesterase inhibition therapy restored cardiac function and and cellular contractile function of α<sub>2A</sub>/α<sub>2C–</sub>KO mice to control levels. *p<0.05 when compared to WT and α<sub>2A</sub>/α<sub>2C–</sub>KO/PYR.</p
Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of th... more Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of the fetus' full growth potential and occurs in a natural and severe manner in pigs as a result of placental insufficiency. Reduced skeletal muscle mass in the fetus with IUGR persists into adulthood and may contribute to increased metabolic disease risk. To investigate skeletal muscle postnatal development, histomorphometrical patterns of the semitendinosus muscle, myosin heavy chain (MyHC; embryonic I, IIA, IIB and IIX isoforms) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100 days old), hypertrophy (100–150 days old), and postnatal development (newborn to 150 days old) were evaluated in female pigs with IUGR and normal birth weight (NW) female littermates. NW females presented higher body weights compared to their IUGR counterparts at all ages evaluated (P < 0.05). Moreover, growth restriction in utero affected the semitendinosus muscle weight, muscle fiber diameter, and muscle cross‐sectional area, which were smaller in IUGR pigs at birth (P < 0.05). Notwithstanding the effects on muscle morphology, IUGR also affected muscle fiber composition, as the percentage of MyHC‐I myofibers was higher at birth (P < 0.05), and, in 150‐day‐old gilts, a lower percentage of MyHC‐IIX isoform (P < 0.05) and the presence of embryonic MyHC isoform were also observed. Regarding the pattern of gene expression in both the postnatal myogenesis and postnatal development periods, IUGR led to the downregulation of myogenic factors, which delayed skeletal muscle myogenesis (PAX7, MYOD, MYOG, MYF5 and DES). Altogether, growth restriction in utero affects muscle fiber number and size at birth and muscle fiber composition through the downregulation of myogenic factors, which determines the individual´s postnatal growth rate. This fact, associated with delayed myofiber development in growth‐restricted animals, may affect meat quality characteristics in animal production. Hence, knowledge of the morphofunctional phenotype of the skeletal muscle throughout postnatal development in individuals with IUGR, and the mechanism that governs it, may provide a better understanding of the mechanisms that limit postnatal muscle growth, and help the establishment of potential strategies to improve muscle development and prevent the onset of later‐life metabolic diseases.
Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of th... more Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of the fetus full growth potential and occurs in a natural and severe manner in pigs. Knowledge on skeletal muscle morphofunctional phenotype and its molecular regulation in IUGR pigs is important to understand postnatal muscle development and may help the establishment of therapies to improve skeletal muscle growth in those individuals. To investigate the impairment of skeletal muscle postnatal development due to IUGR, we evaluated the histomorphometrical pattern of the semitendinosus muscle, the Myosin Heavy Chain (embryonic, I, IIa, IIb and IIx MyHC) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100 days of age), postnatal development (newborn to 150 days of age), and hypertrophy (100 days to 150 days of age), comparing IUGR and normal birth weight (NW) pigs. Growth restr...
Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients wit... more Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC. Forty-nine patients with ChC (50 ± 7 years, New York Heart Association "NYHA" I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression. After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval ...
Chagas disease is an infection caused by the parasite Trypanosoma cruzi that affects millions of ... more Chagas disease is an infection caused by the parasite Trypanosoma cruzi that affects millions of people worldwide and is endemic in Latin America. Megacolon is the most frequent complication of the digestive chronic form and happens due to lesions of the enteric nervous system. The neuronal lesions seem to initiate in the acute phase and persist during the chronic phase, albeit the mechanisms involved in this process are still debated. Among the cells of the immune system possibly involved in this pathological process is the mast cell (MC) due to its well-known role in the bi-directional communication between the immune and nervous systems. Using ultrastructural analysis, we found an increased number of degranulated MCs in close proximity to nerve fibers in infected patients when compared with uninfected controls. We also immunostained MCs for the two pro-inflammatory molecules tryptase and chymase, the first being also important in neuronal death. The number of MCs immunostained fo...
PnPP-19 is a 19-amino-acid synthetic peptide previously described as a novel drug for the treatme... more PnPP-19 is a 19-amino-acid synthetic peptide previously described as a novel drug for the treatment of erectile dysfunction. The aim of this work was to evaluate the physicochemical properties of cationic transfersomes containing PnPP-19 and the skin permeation of free PnPP-19 and PnPP-19-loaded transfersomes. Three different liposomal preparation methods were evaluated. Cationic transfersomes contained egg phosphatidyl choline: stearylamine (9:1 w/w) and Tween 20 (84.6:15.4 lipid:Tween, w/w). Lipid concentration varied from 20 to 40 mM. We evaluated the entrapment percentage, mean diameter, zeta potential and stability at 4 oC of the formulations. The skin permeation assays were performed with abdominal human skin using Franz diffusion cell with 3 cm2 diffusion area at 32 oC and a fluorescent derivative of the peptide, containing 5-TAMRA, bound to PnPP-19 C-terminal region, where an extra lysine was inserted. Our results showed variable entrapment efficiencies, from 6% to 30%, depe...
Although cardiac dysautonomia is a distinctive feature of Chagas disease, its clinical and functi... more Although cardiac dysautonomia is a distinctive feature of Chagas disease, its clinical and functional significance is still being speculated. Neurotrophic factors are potentially involved; however, studies of their effect in this infection are rare. Ultrastructural abnormalities in autonomic varicosities, levels of both nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF), as well as the expression of their receptors, were analysed in the heart of a rat model of Trypanosoma infection. Predominantly, at the early stage of the infection, cardiac autonomic varicosities displayed several signs of degeneration parallel to the elevation of cardiac levels of NGF, as well as expression of the receptors TrkA and p75NTR. For BDNF and TrkB, the changes were less conspicuous. Data obtained here can contribute to further clarify the factors related to the autonomic nervous system's adaptive changes that could determine the evolution of different clinical forms of Chagas di...
Background Aerobic exercise, even for short durations, may promote an increase in serum concentra... more Background Aerobic exercise, even for short durations, may promote an increase in serum concentrations of brain-derived neurotrophic factor (BDNF). However, it is necessary to determine the optimal exercise types and intensities to increase BDNF levels. Objectives This aim of this study was investigate the effects of mild and moderate intensity acute aerobic exercise on serum BDNF levels in patients in the chronic post-stroke phase. Methods The participants answered a socio-demographic questionnaire, cognitive assessment (Mini Mental State Examination), assessment of depressive symptoms (Hamilton Depression Scale), fatigue (Fatigue Severity Scale) and functional capacity (6-minute walk test). Blood samples were collected before and after each session. The measurement of the concentration of BDNF was performed using the enzyme-linked immunosorbent assay . Patients were asked to walk for 30-min in the target training zone (mild intensity, 50-63% of maximum heart rate, and moderate int...
The etiology of trigeminal neuropathic pain is not clear, but there is evidence that demyelinatio... more The etiology of trigeminal neuropathic pain is not clear, but there is evidence that demyelination, expression of cytokines, neuropeptides, and neurotrophic factors are crucial contributors. In order to elucidate mechanisms underlying trigeminal neuropathic pain, we evaluated the time course of morphological changes in myelinated and unmyelinated trigeminal nerve fibers, expression of cytokine IL-1β, neuropeptide substance P (SP), nerve growth factor (NGF), and glial derived neurotrophic factor (GDNF) in peripheral and ganglion tissues, using a rat model of trigeminal neuropathic pain. Chronic constriction injury (CCI) of the infraorbital nerve (IoN), or a sham surgery, was performed. Mechanical allodynia was evaluated from day 3 to day 15 post-surgery. Trigeminal nerves were divided into 2 sections - distal to CCI and ganglion - for morphological analyses, immunohistochemistry (IL-1β, SP), and protein quantification by ELISA (NGF, GDNF). At early postoperative time points, decrease...
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Papers by Patricia Martinelli