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2.
Braz. j. oral sci ; 23: e249184, 2024. tab
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1553451

RESUMO

Aim: This study aimed to review the scientific literature to describe the main care and hygiene protocols for different types of maxillofacial prostheses (MFP). Methods: A bibliographic search on the PubMed / Medline database using the following keywords: ["maxillofacial prosthesis" OR "ocular prostheses" OR "palatal obturators"] AND ["Cleaning" OR "disinfection"] AND ["care"] AND ["color stability"] OR ["denture cleansers" OR "cleansing agents"]. Articles addressing materials, cleaning and disinfection protocols, and care related to MFP were included. The following exclusion criteria were applied: no adequate methodology, incompatibility with the area of interest, and unavailability for reading in full. Results: The papers were grouped into the following topics: facial prostheses, ocular prostheses, maxillofacial intraoral prostheses, and retention systems. Conclusion: Despite the MFP changes over time, its degradation decreases upon following the recommendations and post-adaptation care. The guidelines for cleaning and disinfection must be individualized to guarantee the longevity of the prosthesis and the patient health


Assuntos
Obturadores Palatinos , Prótese Ossicular , Desinfecção , Higiene , Implante de Prótese Maxilofacial , Prótese Maxilofacial
3.
Materials (Basel) ; 16(21)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37959644

RESUMO

The behaviour of geosynthetics can be affected by many agents, both in the short and long term. Mechanical damage caused by repeated loading or abrasion are examples of agents that may induce undesirable changes in the properties of geosynthetics. The research conducted in this work complemented previous studies and consisted of submitting a geocomposite, isolated and successively, to two degradation tests: mechanical damage under repeated loading and abrasion. The geocomposite (a nonwoven geotextile reinforced with polyethylene terephthalate filaments) was tested on both sides (with or without filaments) and directions (machine and cross-machine). The impact of the degradation tests on the geocomposite was quantified by monitoring changes in its tensile and tearing behaviour. The results showed that, in most cases, the degradation tests caused the deterioration of the tensile and tearing behaviour of the geocomposite, affecting its reinforcement function. The decline in tensile strength correlated reasonably well with the decline in tearing strength. Changing the side and direction tested influenced, in some cases (those involving abrasion), the degradation experienced by the geocomposite. The reduction factors (referring to tensile and tearing strength) for the combined effect of the degradation agents tended to be lower when determined by using the common method (compared to those resulting directly from the successive exposure to both agents).

4.
Front Neurol ; 14: 1212185, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37426438

RESUMO

Background: The use of objective gait and balance metrics is rapidly expanding for evaluation of atypical parkinsonism, and these measures add to clinical observations. Evidence for rehabilitation interventions to improve objective measures of balance and gait in atypical parkinsonism is needed. Aim: Our aim is to review, with a narrative approach, current evidence on objective metrics for gait and balance and exercise interventions in progressive supranuclear palsy (PSP). Methods: Literature searches were conducted in four computerized databases from the earliest record up to April 2023: PubMed, ISI's Web of Knowledge, Cochrane's Library, and Embase. Data were extracted for study type (cross-sectional, longitudinal, and rehabilitation interventions), study design (e.g., experimental design and case series), sample characteristics, and gait and balance measurements. Results: Eighteen gait and balance (16 cross-sectional and 4 longitudinal) and 14 rehabilitation intervention studies were included. Cross-sectional studies showed that people with PSP have impairments in gait initiation and steady-state gait using wearable sensors, and in static and dynamic balance assessed by posturography when compared to Parkinson's disease (PD) and healthy controls. Two longitudinal studies observed that wearable sensors can serve as objective measures of PSP progression, using relevant variables of change in turn velocity, stride length variability, toe off angle, cadence, and cycle duration. Rehabilitation studies investigated the effect of different interventions (e.g., balance training, body-weight supported treadmill gait, sensorimotor training, and cerebellar transcranial magnetic stimulation) on gait, clinical balance, and static and dynamic balance assessed by posturography measurements. No rehabilitation study in PSP used wearable sensors to evaluate gait and balance impairments. Although clinical balance was assessed in 6 rehabilitation studies, 3 of these studies used a quasi-experimental design, 2 used a case series, only 1 study used an experimental design, and sample sizes were relatively small. Conclusion: Wearable sensors to quantify balance and gait impairments are emerging as a means of documenting progression of PSP. Robust evidence for improving balance and gait in PSP was not found for rehabilitation studies. Future powered, prospective and robust clinical trials are needed to investigate the effects of rehabilitation interventions on objective gait and balance outcomes in people with PSP.

5.
Cells ; 12(13)2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37443792

RESUMO

Circadian rhythms in behavior and physiology such as rest/activity and hormones are driven by an internal clock and persist in the absence of rhythmic environmental cues. However, the period and phase of the internal clock are entrained by the environmental light/dark cycle. Consequently, aberrant lighting conditions, which are increasing in modern society, have a strong impact on rhythmic body and brain functions. Mice were exposed to three different lighting conditions, 12 h light/12 h dark cycle (LD), constant darkness (DD), and constant light (LL), to study the effects of the light/dark cycle and aberrant lighting on the hippocampus, a critical structure for temporal and spatial memory formation and navigation. Locomotor activity and plasma corticosterone levels were analyzed as readouts for circadian rhythms. Spatial working memory via Y-maze, spine morphology of Golgi-Cox-stained hippocampi, and plasticity of excitatory synapses, measured by number and size of synaptopodin and GluR1-immunreactive clusters, were analyzed. Our results indicate that the light/dark cycle drives diurnal differences in synaptic plasticity in hippocampus. Moreover, spatial working memory, spine density, and size and number of synaptopodin and GluR1 clusters were reduced in LL, while corticosterone levels were increased. This indicates that acute constant light affects hippocampal function and synaptic plasticity.


Assuntos
Luz , Memória Espacial , Camundongos , Animais , Memória de Curto Prazo , Corticosterona , Hipocampo
6.
Cureus ; 15(5): e39526, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37366456

RESUMO

Intussusception occurs when a part of the intestine slides into its distal adjacent portion and is a surgical emergency. Adult colocolic intussusception is rare, but it is a severe condition and is usually associated with a presence of a tumoral process. We present the case of a frail male patient admitted to our emergency department with abdominal pain, prostration, and dyspnea. The patient was diagnosed with colocolic intussusception and was submitted to a subtotal colectomy and ileostomy. Patients with colocolic intussusception usually present with chronic abdominal pain and signs of intestinal obstruction. Abdominal CT scan facilitates the diagnosis, but most cases are only diagnosed intraoperatively. Given the high probability of colon cancer, the treatment involves an oncological resection of the intestinal segment. Colocolic intussusception is a rare cause of intestinal obstruction in adults where a high suspicion index is of paramount importance, especially considering that most of the diagnoses are made at surgery.

7.
Biomater Adv ; 145: 213275, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608438

RESUMO

The development of new cancer treatment options, such as multifunctional devices, allows for a more personalized treatment, avoiding the known severe side effects of conventional options. In this context, on-demand drug delivery systems can actively control the rate of drug release offering a precise control of treatment. Magnetically and thermally controlled drug delivery systems have been explored as on-demand devices to treat chronic diseases and cancer tumors. In the present work, dual-stimuli responsive systems were developed by incorporating Fe3O4 magnetic nanoparticles (NPs) and poly(N-isopropylacrylamide) (PNIPAAm) microgels into electrospun polymeric fibers for application in cancer treatment. First, Fe3O4 NPs with an average diameter of 8 nm were synthesized by chemical precipitation technique and stabilized with dimercaptosuccinic acid (DMSA) or oleic acid (OA). PNIPAAm microgels were synthesized by surfactant-free emulsion polymerization (SFEP). Poly(vinyl alcohol) (PVA) was used as a fiber template originating fibers with an average diameter of 179 ± 14 nm. Stress tests of the membranes showed that incorporating both microgels and Fe3O4 NPs in electrospun fibers increases their Young's modulus. Swelling assays indicate that PVA membranes have a swelling ratio of around 3.4 (g/g) and that the presence of microgels does not affect its swelling ability. However, with the incorporation of Fe3O4 NPs, the swelling ratio of the membranes decreases. Magnetic hyperthermia assays show that a higher concentration of NPs leads to a higher heating ability. The composite membrane with the most promising results is the one incorporated with DMSA-coated NPs, since it shows the highest temperature variation, 5.1 °C. To assess the membranes biocompatibility and ability to promote cell proliferation, indirect and direct contact cell viability assays were performed, as well as cell adhesion assays. Following an extract method viability assay, all membrane designs did not reveal cytotoxic effects on dermal fibroblasts and melanoma cancer cells, after 48 h exposure and support long-term viability. The present work demonstrates the potential of dual-stimuli composite membranes for magnetic hyperthermia and may in the future be used as an alternative cancer treatment particularly in anatomically reachable solid tumors.


Assuntos
Hipertermia Induzida , Microgéis , Nanofibras , Neoplasias , Álcool de Polivinil , Fenômenos Magnéticos
8.
Virology ; 578: 1-6, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36423573

RESUMO

PB1 influenza virus retain traces of interspecies transmission and adaptation. Previous phylogenetic analyses highlighted mutations L298I, R386K and I517V in PB1 to have putatively ameliorated the A(H1N1)pdm09 adaptation to the human host. This study aimed to evaluate the reversal of these mutations and infer the role of these residues in the virus overall fitness and adaptation. We generate PB1-mutated viruses introducing I298L, K386R and V517I mutations in PB1 and evaluate their phenotypic impact on viral growth and on antigen yield. We observed a decrease in viral growth accompanied by a reduction in hemagglutination titer and neuraminidase activity, in comparison with wt. Our data indicate that the adaptive evolution occurred in the PB1 leads to an improved overall viral fitness; and such biologic advantaged has the potential to be applied to the optimization of influenza vaccine seed prototypes.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Filogenia , Proteínas Virais/genética , Vírus da Influenza A/genética , Vacinas contra Influenza/genética
9.
Pharm Pract (Granada) ; 20(2): 2650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919807

RESUMO

Background: Therapy management in patients suffering from mental health disorders is complex and the risks derived from changes or interruptions of treatment should not be ignored. Medication reconciliation in psychiatry may reduce medication errors and promote patient safety during transitions of care. Objective: To identify the influence of complementary information sources in the construction of the best possible medication history, and to ascertain the potential clinical impact of discrepancies identified in a medication reconciliation service. Methods: An observational study was conducted in an acute mental hospital unit, with a further validation in an internal medicine unit. Adult patients taking at least one medicine admitted in the unit were included. Patients/caregivers were interviewed upon admission and the information gathered was compared with hospital medical and shared electronic medical records. Once the best possible medication history was gathered, therapeutic information was reconciled against the prescription on admission to identify discrepancies. Potential clinical impact of medication errors was classified using the International Safety Classification. Results: During the study period, 148 patients were admitted, 50.7% females, mean age 54.6 years (SD=16.3). Collaboration of a caregiver was a needed in 74% of the interviews. In total, 1,147 drugs were considered to obtain patients' best possible medication history. After reconciliation, 560 clinically sound intentional discrepancies were identified and 359 discrepancies required further clarification from prescribers: 84.12% "drug omission", 5.57% "drug substitution", 6.96% "dose change", and 3.34% "dosage frequency change". Potential clinical impact of these medication discrepancies was classified as: 95 mild, 100 moderate, and 29 severe medication errors. Conclusion: About 1 in three intentional discrepancies observed in a pharmacists-led medication reconciliation service required further clarification from prescribers, being 80% of them unintentional discrepancies. Results highlight the importance of the caregiver as source of information for the psychiatric patient, the relevance of analyzing shared electronic health records until 6 months before, and the need to use hospital medical records efficiently. Additionally, 29 discrepancies were classified as errors with potentially severe clinical impact. A medication reconciliation service is concluded to be feasible and necessary in a mental health unit.

10.
PLoS One ; 17(7): e0269438, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35877611

RESUMO

Bayesian skyline plots (BSPs) are a useful tool for making inferences about demographic history. For example, researchers typically apply BSPs to test hypotheses regarding how climate changes have influenced intraspecific genetic diversity over time. Like any method, BSP has assumptions that may be violated in some empirical systems (e.g., the absence of population genetic structure), and the naïve analysis of data collected from these systems may lead to spurious results. To address these issues, we introduce P2C2M.Skyline, an R package designed to assess model adequacy for BSPs using posterior predictive simulation. P2C2M.Skyline uses a phylogenetic tree and the log file output from Bayesian Skyline analyses to simulate posterior predictive datasets and then compares this null distribution to statistics calculated from the empirical data to check for model violations. P2C2M.Skyline was able to correctly identify model violations when simulated datasets were generated assuming genetic structure, which is a clear violation of BSP model assumptions. Conversely, P2C2M.Skyline showed low rates of false positives when models were simulated under the BSP model. We also evaluate the P2C2M.Skyline performance in empirical systems, where we detected model violations when DNA sequences from multiple populations were lumped together. P2C2M.Skyline represents a user-friendly and computationally efficient resource for researchers aiming to make inferences from BSP.


Assuntos
Modelos Genéticos , Teorema de Bayes , Simulação por Computador , Filogenia
11.
Nature ; 606(7913): 396-405, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35650435

RESUMO

Disseminated cancer cells from primary tumours can seed in distal tissues, but may take several years to form overt metastases, a phenomenon that is termed tumour dormancy. Despite its importance in metastasis and residual disease, few studies have been able to successfully characterize dormancy within melanoma. Here we show that the aged lung microenvironment facilitates a permissive niche for efficient outgrowth of dormant disseminated cancer cells-in contrast to the aged skin, in which age-related changes suppress melanoma growth but drive dissemination. These microenvironmental complexities can be explained by the phenotype switching model, which argues that melanoma cells switch between a proliferative cell state and a slower-cycling, invasive state1-3. It was previously shown that dermal fibroblasts promote phenotype switching in melanoma during ageing4-8. We now identify WNT5A as an activator of dormancy in melanoma disseminated cancer cells within the lung, which initially enables the efficient dissemination and seeding of melanoma cells in metastatic niches. Age-induced reprogramming of lung fibroblasts increases their secretion of the soluble WNT antagonist sFRP1, which inhibits WNT5A in melanoma cells and thereby enables efficient metastatic outgrowth. We also identify the tyrosine kinase receptors AXL and MER as promoting a dormancy-to-reactivation axis within melanoma cells. Overall, we find that age-induced changes in distal metastatic microenvironments promote the efficient reactivation of dormant melanoma cells in the lung.


Assuntos
Envelhecimento , Pulmão , Melanoma , Metástase Neoplásica , Células Estromais , Microambiente Tumoral , Idoso , Envelhecimento/patologia , Fibroblastos/patologia , Humanos , Pulmão/patologia , Melanoma/patologia , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Neoplasia Residual , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Pele/patologia , Células Estromais/patologia , Proteína Wnt-5a , c-Mer Tirosina Quinase , Receptor Tirosina Quinase Axl
12.
Virus Res ; 315: 198795, 2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35504447

RESUMO

Vaccination prevents and reduces the severity of influenza virus infections. Continuous evolution of influenza hemagglutinin (HA) and neuraminidase (NA) supports the virus to evade pre-existing immunity, which demands vaccines to be reformulated every year. Incorporation of polymerase basic protein 1 (PB1) viral RNA (vRNA) of the same origin of HA and NA vRNA has been observed in previous pandemic viruses and occasionally reported for influenza A vaccine prototype strains of prior seasons. At this point, it remains to be explored whether this phenomenon translates into an improved growth phenotype. In this work, we showed that the HA vRNA of A(H1N1)pdm09 is generally incorporated with the PB1 vRNA of the same origin, establishing the beneficial effect of the presence of PB1 and the pattern of the PB1-HA co-incorporation in the A(H1N1)pdm09 model. We further investigated the putative interplay between PB1 and antigenic proteins regarding the vRNA composition of the progeny and observed that vRNA segregation does not appear to be mainly determined by protein-protein interactions; while vRNA-vRNA interactions can be suggested as the main driving force. Our data also indicate an increase in the hemagglutination capacity and neuraminidase activity due to incorporation of PB1, HA and NA from A(H1N1)pdm09, in comparison with the recombinant virus incorporating only HA and NA from A(H1N1)pdm09 - which have the potential to improve current limitations regarding antigenicity and immunogenicity of influenza vaccines. Further knowledge of the complex vRNA-vRNA interaction network between PB1 and HA will additionally contribute to improve current vaccine formulation, and to gradually optimize the production of A(H1N1)pdm09 reverse genetics vaccine seed virus towards a higher cost-effectiveness.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Hemaglutininas , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vacinas contra Influenza/genética , Neuraminidase/genética , RNA Viral/genética , Proteínas Virais/metabolismo
13.
Pharm. pract. (Granada, Internet) ; 20(2): 1-6, Apr.-jun. 2022. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-210415

RESUMO

Background: Therapy management in patients suffering from mental health disorders is complex and the risks derived from changes or interruptions of treatment should not be ignored. Medication reconciliation in psychiatry may reduce medication errors and promote patient safety during transitions of care. Objective: To identify the influence of complementary information sources in the construction of the best possible medication history, and to ascertain the potential clinical impact of discrepancies identified in a medication reconciliation service. Methods: An observational study was conducted in an acute mental hospital unit, with a further validation in an internal medicine unit. Adult patients taking at least one medicine admitted in the unit were included. Patients/caregivers were interviewed upon admission and the information gathered was compared with hospital medical and shared electronic medical records. Once the best possible medication history was gathered, therapeutic information was reconciled against the prescription on admission to identify discrepancies. Potential clinical impact of medication errors was classified using the International Safety Classification. Results: During the study period, 148 patients were admitted, 50.7% females, mean age 54.6 years (SD=16.3). Collaboration of a caregiver was a needed in 74% of the interviews. In total, 1,147 drugs were considered to obtain patients’ best possible medication history. After reconciliation, 560 clinically sound intentional discrepancies were identified and 359 discrepancies required further clarification from prescribers: 84.12% “drug omission”, 5.57% “drug substitution”, 6.96% “dose change”, and 3.34% “dosage frequency change”. Potential clinical impact of these medication discrepancies was classified as: 95 mild, 100 moderate, and 29 severe medication errors. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Reconciliação de Medicamentos , Erros de Medicação , Saúde Mental , Hospitais Psiquiátricos , Cuidadores , Farmacêuticos
15.
Sports Med ; 52(8): 1789-1815, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35113386

RESUMO

BACKGROUND: Evidence has demonstrated that endurance training (ET) reduces the motor signs of Parkinson's disease (PD). However, there has not been a comprehensive meta-analysis of studies to date. OBJECTIVE: The aim of this study was to compare the effect of ET versus nonactive and active control conditions on motor signs as assessed by either the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) or Movement Disorder Society-UPDRS-III (MDS-UPDRS-III). METHODS: A random-effect meta-analysis model using standardized mean differences (Hedges' g) determined treatment effects. Moderators (e.g., combined endurance and physical therapy training [CEPTT]) and meta-regressors (e.g., number of sessions) were used for sub-analyses. Methodological quality was assessed by the Physiotherapy Evidence Database. RESULTS: Twenty-seven randomized controlled trials (RCTs) met inclusion criteria (1152 participants). ET is effective in decreasing UPDRS-III scores when compared with nonactive and active control conditions (g = - 0.68 and g = - 0.33, respectively). This decrease was greater (within- and between-groups average of - 8.0 and - 6.8 point reduction on UPDRS-III scores, respectively) than the moderate range of clinically important changes to UPDRS-III scores (- 4.5 to - 6.7 points) suggested for PD. Although considerable heterogeneity was observed between RCTs (I2 = 74%), some moderators that increased the effect of ET on motor signs decreased the heterogeneity of the analyses, such as CEPTT (I2 = 21%), intensity based on treadmill speed (I2 = 0%), self-perceived exertion rate (I2 = 33%), and studies composed of individuals with PD and freezing of gait (I2 = 0%). Meta-regression did not produce significant relationships between ET dosage and UPDRS-III scores. CONCLUSIONS: ET is effective in decreasing UPDRS-III scores. Questions remain about the dose-response relationship between ET and reduction in motor signs.


Assuntos
Treino Aeróbico , Doença de Parkinson , Marcha , Humanos , Testes de Estado Mental e Demência , Doença de Parkinson/diagnóstico , Doença de Parkinson/reabilitação , Modalidades de Fisioterapia
16.
Virology ; 565: 106-116, 2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-34773868

RESUMO

Influenza NS1 is a promising anti-influenza target, considering its conserved and druggable structure, and key function in influenza replication and pathogenesis. Notwithstanding, target identification and validation, strengthened by experimental data, are lacking. Here, we further explored our previously designed structure-based antiviral rationale directed to highly conserved druggable NS1 regions across a broad spectrum of influenza A viruses. We aimed to identify NS1-mutated viruses exhibiting a reduced growth phenotype and/or an altered cell apoptosis profile. We found that NS1 mutations Y171A, K175A (consensus druggable pocket 1), W102A (consensus druggable pocket 3), Q121A and G184P (multiple consensus druggable pockets) - located at hot spots amenable for pharmacological modulation - significantly impaired A(H1N1)pdm09 virus replication, in vitro. This is the first time that NS1-K175A, -W102A, and -Q121A mutations are characterized. Our map-and-mutate strategy provides the basis to establish the NS1 as a promising target using a rationale with a higher resilience to resistance development.


Assuntos
Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Proteínas não Estruturais Virais/genética , Replicação Viral , Substituição de Aminoácidos , Animais , Apoptose , Linhagem Celular , Cães , Descoberta de Drogas , Células HEK293 , Interações entre Hospedeiro e Microrganismos , Humanos , Influenza Humana/metabolismo , Células Madin Darby de Rim Canino , Mutação , Infecções por Orthomyxoviridae/metabolismo
17.
Materials (Basel) ; 14(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201998

RESUMO

Geogrids are building materials widely used for soil reinforcement that can be affected by the action of many degradation agents throughout their service life. The potential negative effect of the degradation agents should be properly estimated and accounted for during the design phase. The main aim of this work was to study the influence of mechanical damage under repeated loading on the resistance of geogrids against abrasion. Three geogrids (one extruded and two woven) were exposed in isolation to mechanical damage under repeated loading and abrasion tests, followed by the successive exposure to both degradation tests. The damage suffered by the geogrids was evaluated by visual inspection and by tensile tests. Based on the changes found in tensile strength, reduction factors were determined. The reduction factors obtained directly from the successive exposure were compared to those resulting from a method in which the reduction factors obtained for the isolated effect of each degradation agent were multiplied. Results indicated that the abrasion process tended to be affected by a previous exposure to mechanical damage under repeated loading and that the multiplication of the reduction factors obtained for the isolated effects of the degradation agents may not correctly represent their combined effect.

18.
Gels ; 7(1)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807693

RESUMO

The delivery of multiple anti-cancer agents holds great promise for better treatments. The present work focuses on developing multifunctional materials for simultaneous and local combinatory treatment: Chemotherapy and hyperthermia. We first produced hybrid microgels (MG), synthesized by surfactant-free emulsion polymerization, consisting of Poly (N-isopropyl acrylamide) (PNIPAAm), chitosan (40 wt.%), and iron oxide nanoparticles (NPs) (5 wt.%) as the inorganic component. PNIPAAm MGs with a hydrodynamic diameter of about 1 µm (in their swollen state) were successfully synthesized. With the incorporation of chitosan and NPs in PNIPAAm MG, a decrease in MG diameter and swelling capacity was observed, without affecting their thermosensitivity. We then sought to produce biocompatible and mechanically robust membranes containing these dual-responsive MG. To achieve this, MG were incorporated in poly (vinyl pyrrolidone) (PVP) fibers through colloidal electrospinning. The presence of NPs in MG decreases the membrane swelling ratio from 10 to values between 6 and 7, and increases the material stiffness, raising its Young modulus from 20 to 35 MPa. Furthermore, magnetic hyperthermia assay shows that PVP-MG-NP composites perform better than any other formulation, with a temperature variation of about 1 °C. The present work demonstrates the potential of using multifunctional colloidal membranes for magnetic hyperthermia and may in the future be used as an alternative treatment for cancer.

19.
Pharmaceutics ; 13(3)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800900

RESUMO

Feline mammary carcinoma (FMC) is a common neoplasia in cat, being HER2-positive the most prevalent subtype. In woman's breast cancer, tyrosine kinase inhibitors (TKi) are used as a therapeutic option, by blocking the phosphorylation of the HER2 tyrosine kinase domain. Moreover, clinical trials demonstrated that TKi produce synergistic antiproliferative effects in combination with mTOR inhibitors, overcoming resistance to therapy. Thus, to uncover new chemotherapeutic strategies for cats, the antiproliferative effects of two TKi (lapatinib and neratinib), and their combination with a mTOR inhibitor (rapamycin), were evaluated in FMC cell lines (CAT-M, FMCp and FMCm) and compared with a human breast cancer cell line (SkBR-3). Results revealed that both TKi induced antiproliferative effects in all feline cell lines, by blocking the phosphorylation of EGFR members and its downstream effectors. Furthermore, combined treatments with rapamycin presented synergetic antiproliferative effects. Additionally, the DNA sequence of the her2 TK domain (exons 18 to 20) was determined in 40 FMC tissue samples, and despite several mutations were found none of them were described as inducing resistance to therapy. Altogether, our results demonstrated that TKi and combined protocols may be useful in the treatment of cats with mammary carcinomas, and that TKi-resistant FMC are rare.

20.
Animals (Basel) ; 11(2)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33671894

RESUMO

Feline mammary carcinoma (FMC) is the third most common type of neoplasia in cats, sharing similar epidemiological features with human breast cancer. In humans, histone deacetylases (HDACs) play an important role in the regulation of gene expression, with HDAC inhibitors (HDACis) disrupting gene expression and leading to cell death. In parallel, microtubules inhibitors (MTIs) interfere with the polymerization of microtubules, leading to cell cycle arrest and apoptosis. Although HDACis and MTIs are used in human cancer patients, in cats, data is scarce. In this study, we evaluated the antitumor properties of six HDACis (CI-994, panobinostat, SAHA, SBHA, scriptaid, and trichostatin A) and four MTIs (colchicine, nocodazole, paclitaxel, and vinblastine) using three FMC cell lines (CAT-MT, FMCp, and FMCm), and compared with the human breast cancer cell line (SK-BR-3). HDACis and MTIs exhibited dose-dependent antitumor effects in FMC cell lines, and for all inhibitors, the IC50 values were determined, with one feline cell line showing reduced susceptibility (FMCm). Immunoblot analysis confirmed an increase in the acetylation status of core histone protein HDAC3 and flow cytometry showed that HDACis and MTIs lead to cellular apoptosis. Overall, our study uncovers HDACis and MTIs as promising anti-cancer agents to treat FMCs.

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