Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 38
Filter
1.
PLoS One ; 19(5): e0302735, 2024.
Article in English | MEDLINE | ID: mdl-38787839

ABSTRACT

OBJECTIVES: To analyze diaphragmatic thickness, at end-inspiration and end-expiration, diaphragmatic thickening index and mobility via US under two different modalities of inspiratory muscle loading, in two different modalities of inspiratory muscle loading and different load intensities at full-vital capacity maneuvers and the relationship between diaphragmatic thickness with pulmonary function tests in participants with HF. METHODS: This randomized crossover trial, enrolled with 17 HF subjects, evaluated diaphragm thickness (Tdi, mm), fractional thickness (TFdi, %), and mobility (mm) US during low and high intensities (30% and 60% of maximal inspiratory pressure-MIP) with two modalities of inspiratory muscle loading mechanical threshold loading (MTL) and tapered flow-resistive loading (TFRL). RESULTS: Both MTL and TFRL produced a increase in Tdi, but only with high intensity loading compared to baseline-2.21 (0.26) vs. 2.68 (0.33) and 2.73 (0.44) mm; p = .01. TFdi was greater than baseline under all conditions, except during low intensity of TFRL. Diaphragm mobility was greater than baseline under all conditions, and high intensity of TFRL elicited greater mobility compared to all other conditions. Additionally, baseline Tdi was moderately correlated with pulmonary function tests. CONCLUSIONS: MTL and TFRL modalities elicit similar increases in diaphragm thickness at loads, but only during high intensity loading it was greater than baseline. Diaphragm mobility was significantly greater than baseline under both loads and devices, and at high intensity compared to low intensity, although TFRL produced greater mobility compared to modalities of inspiratory muscle loading. There is an association between diaphragm thickness and pulmonary function tests.


Subject(s)
Cross-Over Studies , Diaphragm , Heart Failure , Inhalation , Humans , Diaphragm/physiopathology , Diaphragm/diagnostic imaging , Diaphragm/physiology , Male , Middle Aged , Female , Heart Failure/physiopathology , Heart Failure/diagnostic imaging , Inhalation/physiology , Aged , Respiratory Function Tests , Respiratory Muscles/physiopathology
2.
PLoS One ; 18(5): e0279310, 2023.
Article in English | MEDLINE | ID: mdl-37141260

ABSTRACT

INTRODUCTION: Current evidence suggests the emergence of a novel syndrome (long COVID syndrome) due to sequels and persistent COVID-19 symptoms. Respiratory muscle training improves respiratory muscle strength, exercise capacity, diaphragm thickness, and dyspnea, especially in patients with decreased respiratory muscle strength. This study aims to evaluate the effectiveness of a protocol for home-based inspiratory muscle training to improve respiratory muscle strength, dyspnea, and quality of life of patients post-COVID-19. METHODS AND ANALYSES: This randomized, controlled, double-blind clinical trial will be conducted at the Instituto de Medicina Tropical of Universidade Federal do Rio Grande do Norte (Brazil). Sample size will be determined using maximal inspiratory pressure after a pilot study with five patients per group (total of 10 patients). Patients included in the study will be evaluated in three moments: pre-training (initial), post-training (three weeks), and retention (24 weeks). The sample will be randomized in two groups: active (IMT using 30% of IMT and load increase of 10% of initial IMT every week. Patients will perform 30 repetitions, twice a day (morning and afternoon), for seven consecutive days, and six weeks) and SHAM (IMT without load). The following measurements will be assessed: anthropometry, respiratory muscle strength, pulmonary volume and capacity, dyspnea, perception of effort and lower limb fatigue, handgrip strength, functional capacity, anxiety, depression, and functional status. After initial evaluation, all patients will receive a POWERbreathe® (POWERbreathe®, HaB Ltd, Southam, UK) device to perform the training. Normality will be verified using Shapiro-Wilk or Kolmogorov-Smirnov, according to the number of patients included. Variables presenting nonparametric distribution will be compared using Wilcoxon (intragroup analysis) and Mann-Whitney test (intergroup analysis), whereas repeated measures two-way ANOVA will be performed in case of parametric distribution. Dunn's post hoc test will be used to identify significant differences in the two-way ANOVA test. PRIMARY OUTCOMES: Respiratory muscle strength, dyspnea, and quality of life of post-COVID-19 patients. SECOND OUTCOMES: Pulmonary function, dyspnea, exercise tolerance, handgrip strength, anxiety, depression, and functional status. TRIAL REGISTRATION: Trial register number NCT05077241.


Subject(s)
COVID-19 , Quality of Life , Humans , Hand Strength , Pilot Projects , Post-Acute COVID-19 Syndrome , Breathing Exercises/methods , Diaphragm , Respiratory Muscles , Dyspnea/therapy , Muscle Strength/physiology , Exercise Tolerance/physiology , Randomized Controlled Trials as Topic
7.
N Engl J Med ; 385(2): 179-186, 2021 Jul 08.
Article in English | MEDLINE | ID: mdl-34161052

ABSTRACT

Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , COVID-19/transmission , COVID-19 Vaccines/immunology , Humans , Immunogenicity, Vaccine , Mutation , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Virulence
8.
Support Care Cancer ; 29(9): 5161-5171, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33611645

ABSTRACT

BACKGROUND: Noninvasive Ventilation (NIV) is a well-established treatment for Acute Respiratory Failure (ARF) in hematological cancer. However, the NIV impact on mortality in patients with solid tumors is unclear. OBJECTIVE: To define the factors associated with NIV failure and mortality and to describe the mortality risk of patients with solid tumors requiring NIV for ARF treatment in the intensive care unit (ICU). METHODS: A retrospective cohort study of patients with solid tumors admitted into an ICU between Jan 2016 and Dec 2017, for cancer treatment, with ARF diagnosis that had used the NIV as first-line treatment. Our primary outcome was ICU and in-hospital mortality. The secondary outcome was NIV failure. A Cox proportional hazards regression was used to identify variables associated with mortality and NIV failure. Kaplan-Meier analyses were performed to demonstrate cumulative survival. RESULTS: A total of 226 patients with solid tumors were included. The ICU and hospital mortality rates were 57.5% and 69.5%, respectively. NIV failed in 52.2% of the patients. The use of vasopressors (HR 2.48 [95% CI: 1.43-4.30] p = 0.001), baseline lactate (HR 1.20 [95% CI: 1.07-1.35] p = 0.003), baseline PaO2/FiO2 ratio (HR1.33 [1.11-1.55] p = 0.002), and NIV success (HR0.17 [95% CI: 0.10-0.27] p = 0.005) was independently associated with hospital mortality. The use of vasopressors (HR 2.58 [95% CI: 1.41-4.73] p = 0.02), NIV duration (HR 0.93 [95% CI: 0.89-0.97] p = 0.003), and baseline lactate (HR 1.13 [95% CI: 1.06-1.20] p = 0.001) was associated with NIV failure. CONCLUSIONS: NIV failure was independently associated with an increase in both ICU and hospital mortality rates. In patients with NIV therapy indication, the duration of this intervention was associated with NIV failure.


Subject(s)
Neoplasms , Noninvasive Ventilation , Respiratory Distress Syndrome , Respiratory Insufficiency , Hospital Mortality , Humans , Intensive Care Units , Neoplasms/complications , Neoplasms/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Retrospective Studies
9.
Front Med (Lausanne) ; 7: 590527, 2020.
Article in English | MEDLINE | ID: mdl-33330550

ABSTRACT

Non-Biological Complex Drugs (NBCDs) are complex non-biological drugs comprised of large high molecular weight molecules and, often, nanoparticular structures (including liposomes and block-copolymer micelles). In the case of NBCDs, the entire complex is the active pharmaceutical ingredient and its properties cannot be fully characterized by physicochemical analysis. Moreover, the manufacturing process is fundamental in creating the correct originator product. The same is true for generic versions of the product. A recent appraisal of approval procedures for NBCDs "follow-on products" approved in Europe shows a diversity of regulatory pathways. In fact, three different abridged application procedures, under European legislation, were used: the generic application procedure of Article 10(1), the hybrid application procedure of Article 10(3), and the biosimilar application procedure of Article 10(4). Three informed consent applications via Article 10(c) from innovator companies of glatiramer acetate and sevelamer carbonate were submitted shortly after the approval of the first follow-on products. Furthermore, a number of "well-established use" applications [via Article 10(a)] were approved for iron sucrose and iron dextran complexes. In order to protect patients from the increased risks of NBCD products and NBCD follow-on products, two complementary approaches should be considered: (i) improving the regulatory procedures and their guidance documents within the pre-registration phase, and (ii) not considering interchangeability whenever clinical data is not available. With regards to the latter, the need for adequate safety and efficacy data might also include risk management programmes within post-approval pharmacovigilance actions. This, however, would depend on a risk appraisal that must be considered for individual medicinal products, based on the nature of the submitted relevant set of safety/efficacy data.

10.
PLoS One ; 14(8): e0220638, 2019.
Article in English | MEDLINE | ID: mdl-31369636

ABSTRACT

BACKGROUND: Maximal inspiratory pressure (PImax) and 6-minutes walk distance test (6MWD) may be more available and feasible alternatives for prognostic assessment than cardiopulmonary testing. We hypothesized that the PImax and 6MWD combination could improve their individual accuracy as risk predictors. We aimed to evaluate PImax ability as a mortality predictor in HF and whether the combination to 6MWD could improve risk stratification. METHODS: Prospective cohort from HF Clinics of three University Hospitals. PImax, 6MWD and pVO2 were obtained at baseline. The end point was all cause mortality. RESULTS: Consecutive 256 individuals (50% woman, 57.4±10.4years) with low ejection fraction (LVEF) (31.8±8.6%) were followed up to 10years. During a median follow-up of 34.7 (IQR 37) months, 110 participants died. Mean±SD values were: pVO2 14.9±5.1mL/kg/min, PImax 5.5±1.3kPa and 6MWD 372±118m. In multivariate Cox regression, pVO2, PImax, 6MWD and LVEF were independent mortality predictors. The pVO2 showed gold standard accuracy, followed by PImax (AUC = 0.84) and 6MWD (AUC = 0.74). Kaplan-Meier mean survival time (MST±SE) for lower (≤5.0kPa) and higher (>6.0kPa) PImax tertiles, were 37.9±2.8months and 105.0±5.2months respectively, and addition of 6MWD did not restratified risk. For intermediate PImax tertile, MST was 81.5±5.5months, but adding 6MWD, MST was lower (53.3±7.6months) if distance was ≤350m and higher (103.1±5.7months) for longer distances. CONCLUSION: PImax is an independent mortality predictor in HF, more accurate than 6MWD and LVEF. Addition of 6MWD empowers risk stratification only for intermediate PImax tertile. Although less accurate than pVO2, this simpler approach could be a feasible alternative as a prognostic assessment.


Subject(s)
Heart Failure/physiopathology , Inhalation/physiology , Muscle Strength/physiology , Respiratory Muscles/physiopathology , Walk Test , Exercise Test , Female , Follow-Up Studies , Heart Failure/diagnosis , Heart Failure/mortality , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Assessment/methods , Walking/physiology
11.
Regul Toxicol Pharmacol ; 106: 187-196, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31051191

ABSTRACT

An early dialogue between nanomedicine developers and regulatory authorities are of utmost importance to anticipate quality and safety requirements for these innovative health products. In order to stimulate interactions between the various communities involved in a translation of nanomedicines to clinical applications, the European Commission's Joint Research Centre hosted a workshop titled "Bridging communities in the field of Nanomedicine" in Ispra/Italy on the 27th -28th September 2017. Experts from regulatory bodies, research institutions and industry came together to discuss the next generation of nanomedicines and their needs to obtain regulatory approval. The workshop participants came up with recommendations highlighting methodological gaps that should be addressed in ongoing projects addressing the regulatory science of nanomedicines. In addition, individual opinions of experts relevant to progress of the regulatory science in the field of nanomedicine were summarised in the format of a survey.


Subject(s)
Nanomedicine , Decision Making , Decision Support Systems, Clinical , Humans , Surveys and Questionnaires
12.
Appl Physiol Nutr Metab ; 44(8): 879-885, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30649910

ABSTRACT

Step tests are a stressful and feasible cost-effective modality to evaluate aerobic performance. However, the eccentric in addition to concentric muscle contractions of the legs on stepping emerge as a potential speeding factor for cardioventilatory and metabolic adjustments towards a steady-state, since eccentric contractions would prompt an earlier and stronger mechanoreceptor activation, as well as higher heart rate/cardiac output adjustments to the same metabolic demand. Moreover, shorter tests are ideal for exercise-limited subjects. Nine subjects with chronic obstructive pulmonary disease were invited to participate in comprehensive lung function tests and constant work tests performed on different days at a 90% gas exchange threshold for 6 min, in single-step tests or cycle ergometry. After careful monoexponential regression modelling, statistically relevant faster phase II time constants for oxygen uptake (45 ± 18 s vs 53 ± 17 s, p = 0.017) and minute ventilation (61 ± 13 s vs 74 ± 17 s, p = 0.027) were observed in the 6-min step tests compared with cycle ergometry, respectively. Despite an absence of heart rate time constant difference (43 ± 20 s vs 69 ± 46 s, p = 0.167), there was a significantly faster rate constant toward a steady state for heart rate (p = 0.02). In addition, 4-min compared with 6-min analysis presented similar results (p > 0.05), providing an appropriate steady-state. We conclude that step tests might elicit faster time constants compared with cycle ergometry, at the same average metabolic level, and 4-min analysis has similar mean errors compared with 6-min analysis within an acceptable range. New studies, comprising mechanisms and detailed physiological backgrounds, are necessary.


Subject(s)
Ergometry , Exercise , Heart Rate/physiology , Oxygen Consumption/physiology , Oxygen/metabolism , Pulmonary Disease, Chronic Obstructive , Aged , Female , Humans , Male , Middle Aged , Muscle Contraction , Physical Exertion/physiology , Respiratory Function Tests
13.
Clin Respir J ; 12(4): 1598-1606, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28960914

ABSTRACT

INTRODUCTION: Lung hyperinflation is associated with inspiratory muscle strength reduction, nocturnal desaturation, dyspnea, altered cardiac function and poor exercise capacity in advanced COPD. OBJECTIVES: We investigated the responses of inspiratory capacity (IC) and inspiratory muscle strength (PImax), comparing continuous positive airway pressure (CPAP) and expiratory positive airway pressure (EPAP) with the main hypothesis that there would be similar effects on lung deflation. METHODS: Eligible patients were submitted to 10 cmH2 O CPAP and EPAP on different days, under careful ECG (HR) and peripheral oxygen saturation (SpO2 ) monitoring. RESULTS: Twenty-one eligible COPD patients were studied (13 male/8 female, FEV1 % predicted of 36.5 ± 9.8). Both CPAP and EPAP demonstrated significant post-pre (Δ) changes for IC and PImax, with mean ΔIC for CPAP and EPAP of 200 ± 100 mL and 170 ± 105 mL (P = .001 for both) in 13 and 12 patients (responders) respectively. There were similar changes in % predicted IC and PImax (∼7%, P = .001 for both) for responders and poor responder/non-responder agreement depending on CPAP/EPAP mode (Kappa = .113, P = .604). There were no differences in CPAP and EPAP regarding intensity of lung deflation (P =.254) and no difference was measured regarding HR (P = .235) or SpO2 (P = .111). CONCLUSIONS: Both CPAP and EPAP presented a similar effect on lung deflation, without guaranteeing that the response to one modality would be predictive of the response to the other.


Subject(s)
Continuous Positive Airway Pressure/instrumentation , Inspiratory Capacity/physiology , Intermittent Positive-Pressure Ventilation/instrumentation , Lung/physiopathology , Oxygen Consumption/physiology , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Gas Exchange/physiology , Adult , Aged , Aged, 80 and over , Cross-Over Studies , Equipment Design , Female , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests
14.
J Control Release ; 258: 182-195, 2017 07 28.
Article in English | MEDLINE | ID: mdl-28511928

ABSTRACT

Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination with the engraftment of CD4+ and CD8+ T cells, carrying a transgenic OVA-responding T cell receptor (TCR), to trace and characterize the activation of antigen-specific CD4+ and CD8+ lymph node T cells upon NP vaccination. Accordingly, the phenotype and frequency of immune cell stimulation induced by the NP loaded with OVA, isolated or in combination with synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were characterized. DC-NP interactions increased with incubation time, presenting internalization values between 50 and 60% and 30-40%, in vitro and in vivo, respectively. Interestingly, animal immunization with antigen-adsorbed NP up-regulated major histocompatibility complex (MHC) class II (MHCII), while NP entrapping the antigen up-regulated MHCI, suggesting a more efficient cross-presentation. On the other hand, rather surprisingly, the surfactant used in the NP formulation had a major impact on the activation of antigen presenting cells (APC). In fact, DC collected from lymph nodes of animals immunized with NP prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed significantly higher levels of CD86, MHCI and MHCII. In addition, those NP prepared with PVA and co-entrapping OVA and the toll-like receptor (TLR) ligand CpG, induced the most profound antigen-specific T cell response, by both CD4+ and CD8+ T cells, in vivo. Overall, our data reveal the impact of NP composition and surface properties on the type and extension of induced immune responses. Deeper understanding on the NP-immune cell crosstalk can guide the rational development of nano-immunotherapeutic systems with improved and specific therapeutic efficacy and avoiding off-target effects.


Subject(s)
Antigens/administration & dosage , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Dendritic Cells/immunology , Lactic Acid/chemistry , Nanoparticles/chemistry , Ovalbumin/administration & dosage , Polyglycolic Acid/chemistry , Animals , Antigens/immunology , Cytokines/immunology , Drug Delivery Systems , Female , Immunization , Lymph Nodes/cytology , Lymph Nodes/immunology , Lymphocyte Activation , Mice, Inbred C57BL , Nanoparticles/ultrastructure , Ovalbumin/immunology , Polylactic Acid-Polyglycolic Acid Copolymer , Surface-Active Agents/chemistry
15.
Acta Biomater ; 48: 41-57, 2017 01 15.
Article in English | MEDLINE | ID: mdl-27826003

ABSTRACT

Poly(lactic acid) (PLA) is one of the most successful and versatile polymers explored for controlled delivery of bioactive molecules. Its attractive properties of biodegradability and biocompatibility in vivo have contributed in a meaningful way to the approval of different products by the FDA and EMA for a wide range of biomedical and pharmaceutical applications, in the past two decades. This polymer has been widely used for the preparation of particles as delivery systems of several therapeutic molecules, including vaccines. These PLA vaccine carriers have shown to induce a sustained and targeted release of different bacterial, viral and tumor-associated antigens and adjuvants in vivo, triggering distinct immune responses. The present review intends to highlight and discuss the major advantages of PLA as a promising polymer for the development of potent vaccine delivery systems against pathogens and cancer. It aims to provide a critical discussion based on preclinical data to better understand the major effect of PLA-based carrier properties on their interaction with immune cells and thus their role in the modulation of host immunity. STATEMENT OF SIGNIFICANCE: During the last decades, vaccination has had a great impact on global health with the control of many severe diseases. Polymeric nanosystems have emerged as promising strategies to stabilize vaccine antigens, promoting their controlled release to phagocytic cells, thus avoiding the need for multiple administrations. One of the most promising polymers are the aliphatic polyesters, which include the poly(lactic acid). This is a highly versatile biodegradable and biocompatible polymer. Products containing this polymer have already been approved for all food and some biomedical applications. Despite all favorable characteristics presented above, PLA has been less intensively discussed than other polymers, such as its copolymer PLGA, including regarding its application in vaccination and particularly in tumor immunotherapy. The present review discusses the major advantages of poly(lactic acid) for the development of potent vaccine delivery systems, providing a critical view on the main properties that determine their effect on the modulation of immune cells.


Subject(s)
Immunomodulation/drug effects , Nanoparticles/chemistry , Polyesters/pharmacology , Animals , Humans , Immunity/drug effects , Nanotechnology , Vaccines/administration & dosage
16.
J Biomed Nanotechnol ; 12(3): 405-34, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27280242

ABSTRACT

In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking immune tolerance. Immunotherapy has been, for the last two decades, an attractive and promising therapeutic approach to fight cancer. This review will approach the nature of the immune response during cancer development and its correlation with DC function, as well as cancer vaccine principles and limitations. An overview of several delivery strategies used for in vivo modulation of DCs and direct activation of T cells will be provided, highlighting their advantages, limitations, and optimization strategies. This manuscript also presents a critical and systematic review of recent clinical trials that are investigating the therapeutic effect of these approaches, discussing prognostic outcomes of combined-treatment modalities.


Subject(s)
Dendritic Cells/drug effects , Dendritic Cells/immunology , Immunotherapy/methods , Molecular Targeted Therapy/methods , Nanoparticles/therapeutic use , Neoplasms/immunology , Neoplasms/therapy , Animals , Humans , Neoplasms/pathology , Treatment Outcome
17.
Pharm Res ; 33(6): 1351-8, 2016 06.
Article in English | MEDLINE | ID: mdl-27033349

ABSTRACT

PROPOSE: Tin complexes demonstrate antiproliferative activities in some case higher than cisplatin, with IC50 at the low micromolar range. We have previously showed that the cyclic trinuclear complex of Sn(IV) bearing an aromatic oximehydroxamic acid group [nBu2Sn(L)]3 (L=N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) (MG85) shows high anti-proliferative activity, induces apoptosis and oxidative stress, and causes destabilization of tubulin microtubules, particularly in colorectal carcinoma cells. Despite the great efficacy towards cancer cells, this complex still shows some cytotoxicity to healthy cells. Targeted delivery of this complex specifically towards cancer cells might foster cancer treatment. METHODS: MG85 complex was encapsulated into liposomal formulation with and without an active targeting moiety and cancer and healthy cells cytotoxicity was evaluated. RESULTS: Encapsulation of MG85 complex in targeting PEGylated liposomes enhanced colorectal carcinoma (HCT116) cancer cell death when compared to free complex, whilst decreasing cytotoxicity in non-tumor cells. Labeling of liposomes with Rhodamine allowed assessing internalization in cells, which showed significant cell uptake after 6 h of incubation. Cetuximab was used as targeting moiety in the PEGylated liposomes that displayed higher internalization rate in HCT116 cells when compared with non-targeted liposomes, which seems to internalize via active binding of Cetuximab to cells. CONCLUSIONS: The proposed formulation open new avenues in the design of innovative transition metal-based vectorization systems that may be further extended to other novel metal complexes towards the improvement of their anti-cancer efficacy, which is usually hampered by solubility issues and/or toxicity to healthy tissues.


Subject(s)
Antineoplastic Agents/administration & dosage , Colorectal Neoplasms/drug therapy , Drug Delivery Systems/methods , Lipids/chemistry , Liver Neoplasms/drug therapy , Organotin Compounds/administration & dosage , Polyethylene Glycols/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/toxicity , Biological Transport , Cell Proliferation/drug effects , Cell Survival/drug effects , Cetuximab/administration & dosage , Cetuximab/chemistry , Cetuximab/metabolism , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Dose-Response Relationship, Drug , Drug Compounding , HCT116 Cells , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Kinetics , Liposomes , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Organotin Compounds/chemistry , Organotin Compounds/metabolism , Organotin Compounds/toxicity
18.
Trials ; 17: 168, 2016 Mar 29.
Article in English | MEDLINE | ID: mdl-27026087

ABSTRACT

BACKGROUND: Resistant hypertension (RH) treatment requires an adequate and intense therapeutic approach. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of RH, sympathetic overstimulation and therapies that block the sympathetic system have been widely studied. These approaches, however, are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a noninvasive method that modulates activity by using low-frequency transcutaneous electrical stimulation to inhibit primary afferent pathways. Thus, the current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with RH and will seek to develop a new low-cost and readily available therapy to treat this group of hypertensive individuals. METHODS/DESIGN: This is a randomized, single blind (subject), parallel-assignment study controlled with a sham group and including participants aged 40 to 70 years with resistant hypertension. The trial has two arms: the treatment and control (sham group). The treatment group will be submitted to the stimulation procedure (TENS). The sham group will not be submitted to stimulation. The primary outcomes will be a reduction in the peripheral blood pressure and adverse events. The secondary outcomes will be a reduction the central blood pressure. The study will last 30 days. The sample size was calculated assuming an alpha error of 5 % to reject the null hypothesis with a statistical power of 80 %, thereby resulting in 28 participants per group (intervention versus sham). DISCUSSION: In recent decades, RH has become very common and costly. Adequate control requires several drugs, and in many cases, treatment is not successful. Sympathetic nervous system inhibition by renal denervation and central inhibition have significant effects in reducing BP; however, these treatments are costly and invasive. Another type of sympathetic nervous system inhibition can also be noninvasively achieved by electric current. Therefore, the application of TENS may be a new therapeutic option for treating resistant hypertensive individuals. TRIAL REGISTRATION: Clinical Trials NCT02365974.


Subject(s)
Antihypertensive Agents/therapeutic use , Arterial Pressure , Drug Resistance , Hypertension/therapy , Vascular Stiffness , Adult , Aged , Arterial Pressure/drug effects , Brazil , Clinical Protocols , Female , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Male , Middle Aged , Research Design , Single-Blind Method , Time Factors , Transcutaneous Electric Nerve Stimulation/adverse effects , Treatment Outcome , Vascular Stiffness/drug effects
19.
Curr Top Med Chem ; 16(3): 291-313, 2016.
Article in English | MEDLINE | ID: mdl-26126909

ABSTRACT

Cancer is a heterogeneous disease that results from a multi-step process, being characterized by uncontrolled proliferation, invasion and metastasis. The understanding that tumor cells can be recognized by host immune cells has highlighted the potential advantages of using vaccination purposes to eliminate cancer cells, while avoiding severe side effects associated to conventional cancer treatments. Interesting outcomes have been obtained with the new identified tumor associated antigens (TAAs), including recombinant proteins and peptides. However, these molecules are weakly immunogenic, demanding the concomitant use of adjuvants to boost and achieve a strong tumor-specific immune response. Different classes of nanosystems have been used to protect and deliver several vaccine components. In vitro and preclinical studies have emphasized their promising role to attain a prolonged eradication of cancer cells, including metastasis. However, some studies support the co-entrapment of multiple adjuvants and TAAs within a single particulate carrier, while others indicate that stronger immune responses were obtained using a mixture of nanocarriers entrapping different combinations of TAAs and adjuvants. These apparently contradictory results may be related to nanocarrier physicochemical properties, which have a profound impact on their interaction with targeted cells and consequent biological effects. This review discusses the application of nanoscale systems as cancer vaccines, highlighting the particular characteristics of tumor biology and immunology that have been used to guide the design of these nanodelivery tools. We also aim to explore the major weaknesses that have prevented their wide application in the clinic to overcome the delivery, efficacy and safety issues associated to biological entities.


Subject(s)
Cancer Vaccines , Nanomedicine , Neoplasms/therapy , Peptides , Animals , Cancer Vaccines/immunology , Humans , Neoplasms/immunology , Neoplasms/pathology , Peptides/immunology
20.
Fisioter. mov ; 28(3): 429-436, July-Sept. 2015. tab, graf
Article in English | LILACS | ID: lil-763007

ABSTRACT

AbstractIntroduction The purpose of the six-minute walk test (6MWT) is to evaluate cardiopulmonary capacity using a low-cost test that is easy to administer, generally well tolerated by different populations and reflects one’s performance on activities of daily living. However, few studies have been conducted to determine the difference between performing the 6MWT indoors and outdoors.Objective The aim of the present study was to compare the distance covered on the 6MWT performed indoors and outdoors and evaluate the following physiological variables: heart rate, blood pressure and the subjective sensation of shortness of breath, using the Borg perceived exertion scale.Materials and methods A prospective, randomized, clinical trial was conducted involving eight healthy females not engaged in regular physical activity, with mean age 23.75 ± 1.67 years. Each subject performed the 6MWT indoors and outdoors with a 30-minute interval between tests. The order of the tests was determined randomly.Results The mean distance traveled was 578 ± 50.07 m on the outdoor trial and 579.95 ± 45.35 m on the indoor trial (p = 0.932). The mean physiological variables were 82.25 ± 11.02 bpm (indoors) versus 84.38 ± 9.42 bpm (outdoors) for heart rate, 121.88 ± 10.28 mmHg (indoors)versus 118.75 ± 19.40 mmHg (outdoors) for systolic blood pressure, 81.88 ± 9.74 mmHg (indoors) versus 80.50 ± 7.89 mmHg (outdoors) for diastolic blood pressure and a mean score of 12 on the perceived exertion score in both environments.Conclusions The present data demonstrate no differences in the distance walked on the 6MWT or the physiologic variables of participants between the indoor and outdoor trials.


ResumoIntrodução O objetivo do teste de caminhada de seis minutos (TC6) é avaliar a capacidade cardiorrespiratória por meio de um teste de baixo custo e de fácil administração, sendo bem tolerado por diferentes populações, e que reflita a realização das atividades da vida diária. Entretanto, poucos estudos têm sido realizados para determinar a diferença entre a realização do TC6 em ambientes fechados e ao ar livre.Objetivo O presente estudo teve como objetivo comparar a distância percorrida no TC6 realizado em ambientes fechado e ao ar livre e avaliar as seguintes variáveis fisiológicas: frequência cardíaca, pressão arterial e a sensação subjetiva de falta de ar, utilizando a escala de percepção de esforço de Borg.Materiais e métodos Um ensaio clínico randomizado prospectivo foi conduzido envolvendo oito mulheres saudáveis não praticantes de atividade física regular, com média de idade de 23,75 ± 1,67 anos. As participantes realizaram o TC6 nos dois ambientes com um intervalo de 30 minutos entre os testes. A ordem dos testes foi determinada aleatoriamente.Resultados A distância média percorrida foi de 578 ± 50,07 m ao ar livre e 579,95 ± 45,35 m no ambiente fechado (p = 0,932). As variáveis fisiológicas médias foram 82,25 ± 11,02 bpm (fechado) versus 84,38 ± 9,42 bpm (ar livre) para a frequência cardíaca, 121,88 ± 10,28 mmHg (fechado) versus 118,75 ± 19,40 mmHg (ar livre) para a pressão arterial sistólica, 81,88 ± 9,74 mmHg (fechado) versus 80,50 ± 7,89 mmHg (ar livre) para a pressão arterial diastólica e uma pontuação média de 12 pontos na escala de esforço percebido em ambos os ambientes.Conclusão Os dados demonstraram que não há diferenças nas distâncias percorridas ou entre as variáveis fisiológicas dos participantes durante o TC6 nos ambientes fechado e ao ar livre.

SELECTION OF CITATIONS
SEARCH DETAIL
...