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PURPOSE: Physical exercise has positive effects on clinical outcomes of breast cancer survivors such as quality of life, fatigue, anxiety, depression, body mass index, and physical fitness. We aimed to study its impact on immune, inflammatory, cardiometabolic, and fatty acids (FA) biomarkers. METHODS: An exploratory sub-analysis of the MAMA_MOVE Gaia After Treatment trial (NCT04024280, registered July 18, 2019) was performed. Blood sample collections occurred during the control phase and at eight weeks of the intervention phase. Samples were subjected to complete leukocyte counts, cytokine, and cardiometabolic marker evaluation using flow cytometry, enzyme-linked immunoassays, and gas chromatography. RESULTS: Ninety-three percent of the 15 participants had body mass index ≥ 25 kg/m2. We observed a decrease of the plasmatic saturated FA C20:0 [median difference - 0.08% (p = 0.048); mean difference - 0.1 (95%CI - 0.1, - 0.0)], positively associated with younger ages. A tendency to increase the saturated FA C18:0 and the ratio of unsaturated/saturated FA and a tendency to decrease neutrophils (within the normal range) and interferon-gamma were observed. CONCLUSIONS: Positive trends of physical exercise on circulating immune cells, inflammatory cytokines, and plasmatic FA were observed. Larger studies will further elucidate the implications of physical exercise on metabolism. These exploratory findings may contribute to future hypothesis-driven research and contribute to meta-analyses.
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Neoplasias da Mama , Sobreviventes de Câncer , Doenças Cardiovasculares , Humanos , Feminino , Neoplasias da Mama/terapia , Qualidade de Vida , Ácidos Graxos , Exercício Físico , Biomarcadores , CitocinasRESUMO
To assess the effects of a group class physical exercise program on health-related quality of life (HRQOL), physical fitness and activity, and safety in early breast cancer women after treatment, a double-phase trial [16-week control phase (CP) followed by a 16-week intervention phase (IP)] was designed. Outcomes were evaluated at baseline (T1), 8 (T2) and 16 (T3) weeks (CP), and 24 (T4) and 32 (T5) weeks (IP). The primary endpoint was global health status. Out of 82 enrolled patients, 37 completed the IP. Global health status decreased (-10,1; 95% CI -19.8 to -0.4; p = 0.040) during the CP and stabilized during the IP. Physical and sexual functioning increased during the IP (p = 0.008; p = 0.017), while cardiorespiratory fitness increased in the CP (p = 0.004). Upper limb strength and lower limb functionality increased during both phases [CP: p < 0.0001, p = 0.001 (surgical and nonsurgical arm), p = 0.028; IP: p < 0.0001, p = 0.002, p = 0.009]. Body mass index decreased in the IP (p = 0.026). Waist circumference increased in the CP (p = 0.001) and decreased in the IP (p = 0.010); sedentary behaviours and moderate and vigorous physical activity did not change. Adherence to 70% of the sessions was reported in 54% of patients. No serious adverse events related to the intervention were reported. In conclusion, the physical exercise program was able to prevent the decline in global health status and to improve other domains of HRQOL and physical fitness. As physical exercise is not the standard of care in many countries, the implementation of group class programs might be an option.
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Different approaches have been reported to enhance penetration of small drugs through physiological barriers; among them is the self-assembly drug conjugates preparation that shows to be a promising approach to improve activity and penetration, as well as to reduce side effects. In recent years, the use of drug-conjugates, usually obtained by covalent coupling of a drug with biocompatible lipid moieties to form nanoparticles, has gained considerable attention. Natural products isolated from plants have been a successful source of potential drug leads with unique structural diversity. In the present work three molecules derived from natural products were employed as lead molecules for the synthesis of self-assembled nanoparticles. The first molecule is the cytotoxic royleanone 7α-acetoxy-6ß-hydroxyroyleanone (Roy, 1) that has been isolated from hairy coleus (Plectranthus hadiensis (Forssk.) Schweinf). ex Sprenger leaves in a large amount. This royleanone, its hemisynthetic derivative 7α-acetoxy-6ß-hydroxy-12-benzoyloxyroyleanone (12BzRoy, 2) and 6,7-dehydroroyleanone (DHR, 3), isolated from the essential oil of thicket coleus (P. madagascariensis (Pers.) Benth.) were employed in this study. The royleanones were conjugated with squalene (sq), oleic acid (OA), and/or 1-bromododecane (BD) self-assembly inducers. Roy-OA, DHR-sq, and 12BzRoy-sq conjugates were successfully synthesized and characterized. The cytotoxic effect of DHR-sq was previously assessed on three human cell lines: NCI-H460 (IC50 74.0 ± 2.2 µM), NCI-H460/R (IC50 147.3 ± 3.7 µM), and MRC-5 (IC50 127.3 ± 7.3 µM), and in this work Roy-OA NPs was assayed against Vero-E6 cells at different concentrations (0.05, 0.1, and 0.2 mg/mL). The cytotoxicity of DHR-sq NPs was lower when compared with DHR alone in these cell lines: NCI-H460 (IC50 10.3 ± 0.5 µM), NCI-H460/R (IC50 10.6 ± 0.4 µM), and MRC-5 (IC5016.9 ± 0.5 µM). The same results were observed with Roy-OA NPs against Vero-E6 cells as was found to be less cytotoxic than Roy alone in all the concentrations tested. From the obtained DLS results, 12BzRoy-sq assemblies were not in the nano range, although Roy-OA NP assemblies show a promising size (509.33 nm), Pdl (0.249), zeta potential (-46.2 mV), and spherical morphology from SEM. In addition, these NPs had a low release of Roy at physiological pH 7.4 after 24 h. These results suggest the nano assemblies can act as prodrugs for the release of cytotoxic lead molecules.
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Abietanos/química , Abietanos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Animais , Linhagem Celular , Chlorocebus aethiops , Humanos , Hidrocarbonetos Bromados/química , Ácido Oleico/química , Extratos Vegetais/química , Plectranthus/química , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacologia , Esqualeno/química , Testes de Toxicidade Aguda/métodos , Células VeroRESUMO
BACKGROUND: Physical activity is associated with reduced arterial stiffness, although such a relationship has not been reported in those with resistant hypertension. Therefore, this study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension. METHODS: Fifty-seven (57) patients with resistant hypertension (50.9% men), aged 58.8±9.4 years, were consecutively recruited. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). Daily physical activity was objectively assessed with accelerometers during 7 consecutive days. RESULTS: Patients had a body mass index of 29.0±4.0 kg/m2 (84.3% overweight/obese) and were taking an average 4.5 antihypertensive medications. Overall, the cf-PWV was 9.2±2.4 m/s and the majority of participants (n=41, 71.9%) presented a cf-PWV <10 m/s. The cf-PWV showed an inverse correlation with light-intensity physical activity (r = -0.290, p=0.029) and total daily physical activity (r = -0.287, p=0.030). The correlation between light physical activity and cf-PWV remained significant after adjustment for systolic and diastolic blood pressure, but lost significance when further adjusted for age. CONCLUSIONS: Higher daily levels of light-intensity and total physical activity were associated with lower arterial stiffness. Nonetheless, this association is weak and attenuated or abolished when adjusted for blood pressure and age. These results suggest that physical activity may play an important role as a lifestyle intervention for patients with resistant hypertension. Future studies with larger samples sizes are necessary to confirm this preliminary data.
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Hipertensão , Rigidez Vascular , Pressão Sanguínea , Exercício Físico , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Análise de Onda de PulsoRESUMO
The abietane 7α-acetoxy-6ß-hydroxyroyleanone (AHR), obtained from plant extracts, is an attractive lead for drug development, given its known antimicrobial properties. Two basic requirements to establish any compound as a new drug are the development of a convenient extraction process and the characterization of its structural and thermal properties. In this work seven different methods were tested to optimize the extraction of AHR from Plectranthus grandidentatus. Supercritical fluid extraction (SFE) proved to be the method of choice, delivering an amount of AHR (57.351 µg·mg-1) approximately six times higher than the second best method (maceration in acetone; 9.77 µg·mg-1). Single crystal X-ray diffraction analysis of the ARH molecular and crystal structure carried out at 167 ± 2 K and 296 ± 2 K showed only a single phase, here dubbed form III (orthorhombic space group P21212), at those temperatures. The presence of two other polymorphs above room temperature was, however, evidenced by differential scanning calorimetry (DSC). The three forms are enantiotropically related, with the form III â form II and form II â form I transitions occurring at 333.5 ± 1.6 K and 352.0 ± 1.6 K, respectively. The fact that the transitions are reversible suggests that polymorphism is not likely to be an issue in the development pharmaceutical formulations based on ARH. DSC experiments also showed that the compound decomposes on melting at 500.8 ± 0.8 K. Melting should therefore be avoided if, for example, strategies to improve solubility based on the production of glassy materials or solid dispersions are considered.
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Abietanos/química , Antibacterianos/química , Extratos Vegetais/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Cristalização/métodos , Cristalografia por Raios X/métodos , Plectranthus/química , Solubilidade , Temperatura , Difração de Raios X/métodosRESUMO
PURPOSE: The purpose of this study was to analyze the relationship between biological maturation and health-related quality of life (HRQoL) in Portuguese children and adolescents of both sexes when the effect of chronological age (CA) and volume of physical activity (VPA) were removed. METHODS: HRQoL, biological maturation, CA, and VPA were assessed in 750 children and adolescents, 11-17 years old, from 3 schools in Lisbon, Portugal. The KIDSCREEN-52 was used to assess HRQoL. Maturity indicator was bone age (BA), using Tanner-Whitehouse III method (TW3). The participants were classified into three different maturity categories: late, on time, and early maturers. VPA was assessed by questionnaire (RAPIL II). An analysis of covariance (ANCOVA), using the CA and the VPA as covariates was completed. The level of significance was set at p ≤ 0.05. RESULTS: Analysis of covariance suggested an influence of biological maturation in physical well-being dimension in both sexes, with early-maturing girls and boys having worst perception. Maturity groups were also influent in moods and emotions for girls. CA seems to be particularly important in self-perception and parent relation and home life for girls and in school environment for boys. CONCLUSION: Biological maturation and CA have relevant impact on some HRQoL dimensions. These variables, due to their nature and effect should be considered particularly when working with specific domains of HRQoL as physical well-being in both sexes, moods and emotions and self-perception and parent relation and home life for girls and in school environment for boys.
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Exercício Físico/psicologia , Qualidade de Vida/psicologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Portugal , Inquéritos e QuestionáriosRESUMO
Glycyrrhiza glabra L. is considered an important source of bioactive compounds. This study aimed at the development of an efficient solution for the treatment of oral candidiasis. Several extracts of Glycyrrhiza glabra L. were prepared using different solvents and their potential in vitro antifungal activity was assessed. Ethanolic extracts showed the most promising results against C. albicans. This extract was incorporated into mucoadhesive nanoparticles (PLA, PLGA and alginate), which were further included in an oral gel, an oral film and a toothpaste, respectively. The results showed that nanoparticles were successfully produced, presenting a mean size among 100-900 nm with high encapsulation efficiency. In vitro studies showed that the most bioadhesive formulation was the oral film with extract-loaded PLGA nanoparticles, followed by the toothpaste with extract-loaded alginate nanoparticles and the oral gel with extract-loaded PLA nanoparticles.
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Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Glycyrrhiza/química , Nanoestruturas/química , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Formas de Dosagem , Fenômenos Mecânicos , Mucosa Bucal/efeitos dos fármacos , Extratos Vegetais/químicaRESUMO
Aims: To analyze the feasibility and impact of a walking football (WF) program on quality of life (QoL), cardiorespiratory fitness (CRF), muscle strength, and balance program in men with prostate cancer under androgen deprivation therapy (ADT). Methods: Fifty patients with prostate cancer (stages IIb-IVb) under ADT were randomized to a 16-week WF program plus usual care (n=25) or usual care control group (n=25). The WF program consisted of three 90-minute sessions per week. Recruitment, withdrawal, adherence, enjoyment rate, and safety of the intervention were recorded throughout the study. Cardiorespiratory fitness was assessed before and after the interventions, while handgrip strength, lower limb muscle strength, static balance, and QoL were assessed before, during (week 8), and after (week 16) the interventions. Adverse events during sessions were also recorded. Results: The WF group showed high levels of adherence (81.6 ± 15.9%) and enjoyment rate (4.5 ± 0.5 out of 5 points). In the intention-to-treat analysis, the WF group showed an improvement in chair sit-to-stand (p=0.035) compared to the control group. Within-group comparisons showed that handgrip strength in the dominant upper limb (p=0.024), maximal isometric muscle strength in the non-dominant lower limb (p=0.006), and balance in the dominant limb (p=0.009) improved over time in the WF group but not in the usual care group. The results obtained from the per-protocol analysis indicate that CRF improved significantly in the WF group as compared to the control group (p=0.035). Within-group analysis revealed that CRF (p=0.036), muscle strength in dominant (p=0.006) and non-dominant (p=0.001) lower limbs, and balance in the non-dominant lower limb (p=0.023) improved after 16 weeks of WF, but not in the control group. One major traumatic injury (muscle tear) was reported with a complete recovery before the end of the intervention. Conclusion: This study suggests that WF is feasible, safe, and enjoyable in patients with prostate cancer under hormonal therapy. Furthermore, patients who adhere to the WF program can expect cardiorespiratory fitness, muscle strength, and balance improvements. Clinical trials registration: clinicaltrials.gov, identifier NCT04062162.
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Central blood pressure (BP) and BP variability are associated with cardiovascular disease risk. However, the influence of exercise on these hemodynamic parameters is unknown among patients with resistant hypertension. The EnRicH (The Exercise Training in the Treatment of Resistant Hypertension) was a prospective, single-blinded randomized clinical trial (NCT03090529). Sixty patients were randomized to a 12-week aerobic exercise program or usual care. The outcome measures include central BP, BP variability, heart rate variability, carotid-femoral pulse wave velocity, and circulating cardiovascular disease risk biomarkers including high-sensitivity C-reactive protein, angiotensin II, superoxide dismutase, interferon gamma, nitric oxide, and endothelial progenitor cells. Central systolic BP decreased by 12.22 mm Hg (95% CI, -1.88 to -22.57, P = 0.022) as did BP variability by 2.85 mm Hg (95% CI, -4.91 to -0.78, P = 0.008), in the exercise (n = 26) compared to the control group (n = 27). Interferon gamma -4.3 pg/mL (95%CI, -7.1 to -1.5, P = 0.003), angiotensin II -157.0 pg/mL (95%CI, -288.1 to -25.9, P = 0.020), and superoxide dismutase 0.4 pg/mL (95%CI, 0.1-0.6, P = 0.009) improved in the exercise compared to the control group. Carotid-femoral pulse wave velocity, heart rate variability, high-sensitivity C-reactive protein, nitric oxide, and endothelial progenitor cells were not different between groups (P > 0.05). In conclusion, a 12-week exercise training program improved central BP and BP variability, and cardiovascular disease risk biomarkers in patients with resistant hypertension. These markers are clinically relevant as they are associated with target organ damage and increased cardiovascular disease risk and mortality.
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Doenças Cardiovasculares , Hipertensão , Rigidez Vascular , Humanos , Pressão Sanguínea/fisiologia , Proteína C-Reativa , Análise de Onda de Pulso , Óxido Nítrico , Angiotensina II , Interferon gama , Estudos Prospectivos , Hipertensão/terapia , Exercício Físico/fisiologia , Biomarcadores , Superóxido Dismutase , Rigidez Vascular/fisiologiaRESUMO
Background: In non-valvular-associated atrial fibrillation (AF), direct oral anticoagulants (DOAC) are as effective as vitamin K antagonists (VKA) for the prevention of acute ischemic stroke (AIS). DOAC are associated with decreased risk and severity of intracranial hemorrhage. It is unknown if different pre-admission anticoagulants impact the prognosis of AF related AIS (AF-AIS). We sought to analyze the literature to assess the association between pre-admission anticoagulation (VKA or DOAC) and admission severity of AF-AIS. Methods: A Systematic literature search (PubMed and ScienceDirect) between January 2011 to April 2021 was undertaken to identify studies describing the outcome of AF-AIS. Results: A total of 128 articles were identified. Of 9493 patients, 1767 were on DOAC, 919 were on therapeutical VKA, 792 were on non-therapeutical VKA and 6015 were not anticoagulated. In comparison to patients without anticoagulation, patients with therapeutical VKA and under DOAC presented with less severe stroke (MD −1.69; 95% CI [−2.71, −0.66], p = 0.001 and MD −2.96; 95% Cl [−3.75, −2.18], p < 0.00001, respectively). Patients with non-therapeutical VKA presented with more severe stroke (MD 1.28; 95% Cl [0.45, 2.12], p = 0.003). Conclusions: In AF-AIS, patients under therapeutical VKA or DOAC have reduced stroke severity on admission in comparison to patients without any anticoagulation, with higher magnitude of protection for DOAC.
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Kinesins are motor proteins present in organisms from protists to mammals playing important roles in cell division, intracellular organisation and flagellum formation and maintenance. Leishmania mexicana is a protozoan parasite of the order Kinetoplastida causing human cutaneous leishmaniasis. Kinetoplastida genome sequence analyses revealed a large number of kinesins showing sequence and structure homology to eukaryotic kinesins. Here, we investigate the L. mexicana kinesin LmxKIN29 (LmxM.29.0350), also called DEATH kinesin. The activated MAP kinase LmxMPK3, a kinase affecting flagellum length in Leishmania, is able to phosphorylate recombinant full length LmxKIN29 at serine 554. Insect promastigote LmxKIN29 Leishmania null mutants showed no obvious phenotype. However, in mouse infection experiments, the null mutants were unable to cause the disease, whereas LmxKIN29 add-backs and single allele knockouts caused footpad lesions. Localisation using promastigotes expressing GFP-tagged LmxKIN29 revealed that the kinesin is predominantly found in between the nucleus and the flagellar pocket, while in dividing cells the GFP-fusion protein was found at the anterior and posterior ends of the cells indicating a role in cytokinesis. The inability to cause lesions in infected animals and the amino acid sequence divergence from mammalian kinesins suggests that LmxKIN29 is a potential drug target against leishmaniasis.
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Leishmania mexicana , Leishmaniose Cutânea , Animais , Flagelos/metabolismo , Cinesinas/metabolismo , Leishmania mexicana/metabolismo , Leishmaniose Cutânea/metabolismo , Leishmaniose Cutânea/parasitologia , Mamíferos/metabolismo , Camundongos , Proteínas de Protozoários/metabolismoRESUMO
6,7-Dehydroroyleanone (DHR) is a caspase-induced cytotoxic abietane diterpene, frequently found on Plectranthus spp. A pharmaceutical formulation consisting of a DHR-squalene conjugate was synthesized and analyzed by different techniques such as scanning electron microscopy (SEM). The facile production of the dispersion of DHR-squalene conjugate nanoparticles in phosphate buffer (pH 7.4) suggests that this nanodelivery platform may be an effective system to improve the solubility and bioavailability of DHR, so that therapeutical systemic levels may be achieved.
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Head and neck cancer (HNC) treatment's toxicities impact several health domains. Exercise training (ET) may be beneficial. This prospective observational study (NCT04996147) aimed to analyse the acute impact of HNC curative multimodal treatment on health-related quality of life (HRQoL), nutritional status, physical and cognitive functions, and ET preferences. Eighteen patients with stage III/IV HNC were evaluated at baseline (T0), and 10 patients were evaluated at the end of treatment (T1), 7 of them after radical chemoradiotherapy (rCRT). At T0, the majority referred a good HRQoL on the EORTC QLQ-C30 questionnaire (median score: 70.8), were moderately malnourished or at risk of malnutrition (78%), recognized the benefits of an ET program, and were willing to participate (78%). After rCRT, there was worsening in HRQoL (75 vs. 50 score, p = 0.014), dysphagia severity (Eating Assessment Tool: 7 vs. 31, p = 0.027; Functional Oral Intake Scale: 6 vs. 4, p = 0.041), handgrip strength (dominant: 40.9 vs. 35.8 kgf, p = 0.027; nondominant: 37.2 vs. 33.9 kgf, p = 0.043), and nutritional status (Patient-Generated Subjective Global Assessment: 7 vs. 18, p = 0.028). HNC patients subjected to radical treatment represent a vulnerable population that might benefit from multimodal supportive care strategies including an ET program.
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Reports suggest that the blood pressure (BP) response to an acute bout of exercise is associated with the BP response to aerobic training in participants with elevated BP. These associations have not been tested among patients with resistant hypertension. This study aimed to determine whether the BP response to acute exercise predicts the 24-h ambulatory BP response to a 12-week exercise training program in patients with resistant hypertension (n = 26, aged 59.3 ± 8.2 years, 24-h ambulatory BP 127.4 ± 12.2/75.6 ± 7.8 mm Hg) who completed the exercise arm of the EnRicH trial. Ambulatory BP measurements were obtained before and after the exercise program to assess the chronic BP response. To assess acute BP changes, resting BP was measured before and 10 min after three exercise sessions in the third week of training and averaged. The resting systolic (9.4 ± 6.7, p < 0.001) and diastolic BP (1.9 ± 3.2, p = 0.005) were reduced after acute exercise. The 24-h systolic (6.2 ± 12.2, p = 0.015) and diastolic BP (4.4 ± 6.1, p = 0.001) were decreased after exercise training. The reductions in systolic BP after acute exercise were associated with the reductions in 24-h systolic BP after exercise training (ß = 0.538, adjusted r2 = 0.260, P = 0.005). The reductions in diastolic BP after acute exercise (ß = 0.453, adjusted r2 = 0.187) and baseline 24-h diastolic BP (ß = -0.459, adjusted r2 = 0. 199) accounted for 38.6% (p = 0.008) of the 24-h diastolic BP response to exercise training. In conclusion, the magnitude of the BP response to acute exercise appears to predict the ambulatory BP response to exercise training among patients with resistant hypertension.
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Monitorização Ambulatorial da Pressão Arterial , Hipertensão , Pressão Sanguínea/fisiologia , Exercício Físico/fisiologia , Humanos , Hipertensão/terapia , SístoleRESUMO
INTRODUCTION: Guidance for pregnant women has been particularly problematic since the beginning of the COVID-19 pandemic. The aim of this study was to describe the characteristics and outcomes of pregnant women with SARS-CoV-2 infection and their newborns. MATERIAL AND METHODS: Case review of clinical records of pregnant women with SARS-CoV-2 infection admitted for delivery and their newborns from April to December 2020 at a hospital in the Lisbon metropolitan area. RESULTS: From 1755 births, 81 (4.6%) were from SARS-CoV-2 positive mothers. Most (83.9%) were term newborns. Almost 16% were preterm, while there was an overall prematurity rate of 9.9%. Most women (88.6%) were asymptomatic. Rooming-in occurred in 80.8% cases and 19.2% newborns were admitted to the Neonatal Intensive Care Unit. From the total, 56.7% newborns were breastfed from birth and 43% had mixed feeding. None of the newborns had symptoms related to COVID-19 infection, and all had negative rt-PCR for SARS-CoV-2 at birth and at 48 hours of life. The majority (85.2%) was discharged home with their mothers. DISCUSSION: Pregnant women with COVID-19 have shown immune characteristics resembling healthy pregnancies, and it is not yet clear if SARS-CoV-2 can be vertically transmitted. Recent updates on neonatal guidance now recommend rooming-in and support the relative safety of breastfeeding. CONCLUSION: This study supports other published articles regarding maternal and neonatal outcomes of SARS-CoV-2 infected pregnant women, including the absence of short-term adverse outcomes with rooming-in and breastfeeding.
Introdução: Desde o início da pandemia COVID-19, tem sido particularmente dificil obter orientações relativas a mulheres grávidas. Este estudo teve como objetivo descrever as características e resultados clínicos das grávidas com SARS-CoV-2 e dos seus recém--nascidos. Material e Métodos: Revisão de processos clínicos de grávidas com infecção por SARS-CoV-2 admitidas para o parto, e dos seus recém-nascidos, no período de abril a dezembro de 2020 num hospital da área metropolitana de Lisboa. Resultados: De um total de 1755 nascimentos, 81 (4,6%) foram de mães positivas para SARS-CoV-2. A maioria eram recém-nascidos de termo; 16% eram prematuros, sendo a taxa geral de prematuridade 9,9%. A maioria das grávidas (88,6%) foi assintomática. O alojamento conjunto ocorreu em 80,8% dos casos e 19,2% dos recém-nascidos foram admitidos na Unidade de Cuidados Intensivos Neonatais. A maioria dos recém-nascidos (56,7%) fez leite materno desde o nascimento e 43% fez aleitamento misto. Nenhum recém--nascido apresentou sintomas relacionados com a infeção por COVID-19 e todos foram negativos por rt-PCR para SARS-CoV-2 ao nascimento e às 48 horas. Do total, 85,2% dos recém-nascidos tiveram alta para o domicílio com a mãe. Discussão: As grávidas com COVID-19 apresentam características imunológicas semelhantes a grávidas saudáveis e ainda não é clara a transmissão vertical do SARS-CoV-2. Atualizações recentes sobre as orientações neonatais recomendam o alojamento conjunto e apoiam a segurança da amamentação. Conclusão: Este estudo corrobora resultados maternos e neonatais anteriores incluindo a ausência de resultados adversos a curto prazo com alojamento conjunto e amamentação.
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COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Hospitais , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Mães , Pandemias , Portugal/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , SARS-CoV-2RESUMO
OBJECTIVE: Arterial stiffness, namely pulse wave velocity (PWV), is an emerging biomarker in the assessment of vascular health. This meta-analysis aims to determine the effects of exercise training on PWV in patients with hypertension, and to identify the possible moderator variables (e.g. type of exercise) of the effect of exercise on PWV. METHODS: MEDLINE, EMBASE, Cochrane and Web of Science were searched up until July 2019 for randomized controlled trials assessing the effect of exercise interventions lasting 4 or more weeks on PWV in adults with hypertension. Random-effects modelling was used to compare changes from pre to postintervention in PWV between exercise and control groups. Data were reported as weighted mean difference (WMD) and 95% confidence interval (95% CI). Protocol registration: PROSPERO registration number CRD42019138658. RESULTS: We included 14 trials (15 interventions), involving five aerobic, two dynamic resistance, six combined and two isometric resistance groups, totalling 642 participants with hypertension. PWV was significantly reduced by exercise training [(WMD (95% CI)â=â-0.76âm/s (-1.05 to -0.47)]. Analysis of moderator variables showed that aerobic exercise [WMD (95% CI)â=â-0.70âm/s (-1.20 to -0.19)], combined exercise [WMD (95% CI)â=â-0.74âm/s (-1.41 to -0.08)] and isometric resistance exercise [WMD (95% CI)â=â-0.98âm/s (-1.24 to -0.73)] reduced PWV. There was no significant reduction in PWV in participants undertaking dynamic resistance training [WMD (95% CI)â=â-0.58 (-1.58 to 0.42)]. CONCLUSION: This meta-analysis supports that exercise interventions based on aerobic, combined or isometric exercise are suitable to improve PWV in adults with hypertension.
Assuntos
Hipertensão , Treinamento Resistido , Rigidez Vascular , Adulto , Exercício Físico , Humanos , Hipertensão/terapia , Análise de Onda de PulsoRESUMO
Importance: Limited evidence suggests exercise reduces blood pressure (BP) in individuals with resistant hypertension, a clinical population with low responsiveness to drug therapy. Objective: To determine whether an aerobic exercise training intervention reduces ambulatory BP among patients with resistant hypertension. Design, Settings, and Participants: The Exercise Training in the Treatment of Resistant Hypertension (EnRicH) trial is a prospective, 2-center, single-blinded randomized clinical trial performed at 2 hospital centers in Portugal from March 2017 to December 2019. A total of 60 patients with a diagnosis of resistant hypertension aged 40 to 75 years were prospectively enrolled and observed at the hospitals' hypertension outpatient clinic. Interventions: Patients were randomly assigned in a 1:1 ratio to a 12-week moderate-intensity aerobic exercise training program (exercise group) or a usual care control group. The exercise group performed three 40-minute supervised sessions per week in addition to usual care. Main Outcomes and Measures: The powered primary efficacy measure was 24-hour ambulatory systolic BP change from baseline. Secondary outcomes included daytime and nighttime ambulatory BP, office BP, and cardiorespiratory fitness. Results: A total of 53 patients completed the study, including 26 in the exercise group and 27 in the control group. Of these, 24 (45%) were women, and the mean (SD) age was 60.1 (8.7) years. Compared with the control group, among those in the exercise group, 24-hour ambulatory systolic BP was reduced by 7.1 mm Hg (95% CI, -12.8 to -1.4; P = .02). Additionally, 24-hour ambulatory diastolic BP (-5.1 mm Hg; 95% CI, -7.9 to -2.3; P = .001), daytime systolic BP (-8.4 mm Hg; 95% CI, -14.3 to -2.5; P = .006), and daytime diastolic BP (-5.7 mm Hg; 95% CI, -9.0 to -2.4; P = .001) were reduced in the exercise group compared with the control group. Office systolic BP (-10.0 mm Hg; 95% CI, -17.6 to -2.5; P = .01) and cardiorespiratory fitness (5.05 mL/kg per minute of oxygen consumption; 95% CI, 3.5 to 6.6; P < .001) also improved in the exercise group compared with the control group. Conclusions and Relevance: A 12-week aerobic exercise program reduced 24-hour and daytime ambulatory BP as well as office systolic BP in patients with resistant hypertension. These findings provide clinicians with evidence to embrace moderate-intensity aerobic exercise as a standard coadjutant therapy targeting this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03090529.
Assuntos
Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Exercício Físico/fisiologia , Hipertensão/reabilitação , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Estudos Prospectivos , Método Simples-CegoRESUMO
The number of cases of failure in the treatment of infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, 7α-Acetoxy-6ß-hydroxyroyleanone (AHR), a diterpene isolated from different Plectranthus species, showed antibacterial activity, namely against Methicillin-resistant Staphylococcus aureus (MRSA) strains. The high antibacterial activity and low cytotoxicity render this natural compound an interesting alternative against resistant bacteria. The aim of this study is to understand the mechanism of action of AHR on MRSA, using the MRSA/Vancomycin-intermediate S. aureus (VISA) strain CIP 106760, and to study the AHR effect on lipid bilayers and on the cell wall. Although AHR interacted with lipid bilayers, it did not have a significant effect on membrane passive permeability. Alternatively, bacteria treated with this royleanone displayed cell wall disruption, without revealing cell lysis. In conclusion, the results gathered so far point to a yet undescribed mode of action that needs further investigation.
Assuntos
Diterpenos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Vancomicina/efeitos dos fármacos , Membrana Externa Bacteriana , Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacosRESUMO
The development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6ß-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6.
RESUMO
Cancer is among the leading causes of death worldwide. One of the most challenging obstacles in cancer treatment is multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp) is associated with MDR. The growing incidence of cancer and the development of MDR drive the search for novel and more effective anticancer drugs to overcome the MDR problem. Royleanones are natural bioactive compounds frequently found in Plectranthus spp. The cytotoxic diterpene 6,7-dehydroroyleanone (1) is the main component of the P. madagascariensis (Pers.) Benth. essential oil, while 7α-acetoxy-6ß-hydroxyroyleanone (2) can be isolated from acetonic extracts of P. grandidentatus Gürke. The reactivity of the natural royleanones 1 and 2 was explored to obtain a small library of new P-gp inhibitors. Four new derivatives (6,7-dehydro-12-O-tert-butyl-carbonate-royleanone (20), 6,7-dehydro-12-O-methylroyleanone (21), 6,7-dehydro-12-O-benzoylroyleanone (22), and 7α-acetoxy-6ß-hydroxy-12-O-benzoylroyleanone (23) were obtained as pure with overall modest to excellent yields (21-97%). P-gp inhibition potential of the derivatives 20-23 was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R with the P-gp overexpression, through MTT assay. Previously prepared diterpene 7α-acetoxy-6ß-benzoyloxy-12-O-(4-chloro)benzoylroyleanone (4), has also been tested. The P-gp inhibiting effects of compounds 1-4 were also assessed through a Rhodamine 123 accumulation assay. Derivatives 4 and 23 have significant P-gp inhibitory potential. Regarding stability and P-gp inhibition potential, results suggest that the formation of benzoyl esters is a more convenient approach for future derivatives with enhanced effect on the cell viability decrease. Compound 4 presented higher anti-P-gp potential than the natural diterpenes 1, 2, and 3, with comparable inhibitory potential to Dexverapamil. Moreover, derivative 4 showed the ability to sensitize the resistant NCI-H460/R cells to doxorubicin.