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1.
Front Pharmacol ; 15: 1346169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515839

RESUMO

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

2.
Front Immunol ; 15: 1354479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444856

RESUMO

Introduction: The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. Methods: In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. Results: We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-ß1 (M(IL-10+TGF-ß1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-ß1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-ß1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-ß1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Discussion: Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.


Assuntos
Interleucina-10 , Traumatismos da Medula Espinal , Humanos , Animais , Camundongos , Fator de Crescimento Transformador beta1 , Proteômica , Secretoma , Traumatismos da Medula Espinal/terapia
4.
Front Med (Lausanne) ; 10: 1143402, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36993802

RESUMO

Introduction: Leprosy is an infectious disease that remains with a high number of new cases in developing countries. Household contacts have a higher risk for the development of the disease, but the neural impairment in this group is not well elucidated yet. Here, we measured the chance of occurrence of peripheral neural impairment in asymptomatic leprosy household. Methods: Contacts who present anti-PGL-I IgM seropositivity, through electroneuromyography (ENMG) evaluation. We recruited 361 seropositive contacts (SPC) from 2017 to 2021, who were subjected to an extensive protocol that included clinical, molecular, and electroneuromyographic evaluations. Results: Our data revealed a positivity of slit skin smear and skin biopsy qPCR of 35.5% (128/361) and 25.8% (93/361) respectively. The electroneuromyographic evaluation of the SPC showed neural impairment in 23.5% (85/361), with the predominance of a mononeuropathy pattern in 62.3% (53/85). Clinical neural thickening was observed in 17.5% (63/361) of seropositive contacts, but among the individuals with abnormal ENMG, only 25.9% (22/85) presented neural thickening in the clinical exam. Discussion: Ours results corroborates the need to make the approach to asymptomatic contacts in endemic countries more timely. Since leprosy in its early stages can present an indolent and subclinical evolution, serological, molecular, and neurophysiological tools are essential to break the disease transmission chain.

5.
Molecules ; 28(3)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36770876

RESUMO

Heat shock protein 90 (HSP90) facilitates folding and stability and prevents the degradation of multiple client proteins. One of these HSP90 clients is BCR-ABL, the oncoprotein characteristic of chronic myeloid leukemia (CML) and the target of tyrosine kinase inhibitors, such as imatinib. Alvespimycin is an HSP90 inhibitor with better pharmacokinetic properties and fewer side effects than other similar drugs, but its role in overcoming imatinib resistance is not yet clarified. This work studied the therapeutic potential of alvespimycin in imatinib-sensitive (K562) and imatinib-resistant (K562-RC and K562-RD) CML cell lines. Metabolic activity was determined by the resazurin assay. Cell death, caspase activity, mitochondrial membrane potential, and cell cycle were evaluated by means of flow cytometry. Cell death was also analyzed by optical microscopy. HSPs expression levels were assessed by western blotting. Alvespimycin reduced metabolic activity in a time-, dose-, and cell line-dependent manner. Resistant cells were more sensitive to alvespimycin with an IC50 of 31 nM for K562-RC and 44 nM for K562-RD, compared to 50 nM for K562. This drug induced apoptosis via the mitochondrial pathway. In K562 cells, alvespimycin induced cell cycle arrest in G0/G1. As a marker of HSP90 inhibition, a significant increase in HSP70 expression was observed. Our results suggest that alvespimycin might be a new therapeutic approach to CML treatment, even in cases of resistance to imatinib.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Proteínas de Choque Térmico , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo
6.
Stem Cell Rev Rep ; 19(1): 248-263, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36152233

RESUMO

Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative senescence and associated phenotypes, including its effects on MSCs secretome composition and immunomodulatory action. Our results evidence a rejuvenated phenotype of iMSCs, which is translated into a superior proliferative capacity before the induction of replicative senescence. Despite this significant difference between iMSCs and BM-MSCs proliferation, both untargeted and targeted proteomic analysis revealed a similar secretome composition for both sources in pre-senescent and senescent states. These results suggest that shifting from the use of BM-MSCs to a more advantageous source, like iMSCs, may yield similar therapeutic effects as identified over the past years for this gold-standard MSC source.


Assuntos
Medula Óssea , Células-Tronco Mesenquimais , Diferenciação Celular , Proteômica , Secretoma , Senescência Celular
7.
Front Immunol ; 13: 916319, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874693

RESUMO

Mycobacterium leprae, the etiologic agent of leprosy, is an acid-fast-staining and slow-growing bacilli that infect macrophages and Schwann cells individually or through forming globi. The clinical presentation of leprosy is broad and depends on the host immune response. We report a case of a 42-year-old Brazilian man presenting with fever of unknown origin (FUO), anemia, wasting syndrome, and neuropathy. The diagnosis of lepromatous leprosy was made after an extensive investigation revealed the presence of M. leprae in the bone marrow. Bone marrow involvement in leprosy is rare and some authors believe the presence of M. leprae in the bone marrow can act as a reservoir of the disease facilitating future relapses. It is important to investigate bone marrow involvement in leprosy, especially when the patient presents with cytopenias and positive epidemiologic history.


Assuntos
Febre de Causa Desconhecida , Hanseníase , Síndrome de Emaciação , Adulto , Medula Óssea , Caquexia , Humanos , Hanseníase/diagnóstico , Hanseníase/microbiologia , Masculino , Mycobacterium leprae
8.
Polymers (Basel) ; 14(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35566959

RESUMO

In our daily lives and product manufacturing, metal corrosion causes significant economic losses. Numerous polymeric composite coatings have been shown to be resistant to harsh environments, such as those found in marine environments. In this study, a composite of polyvinyl alcohol/polyaniline blend loaded with carboxylated graphene was explored in the search for long-lasting coatings to resist electrochemical deterioration of cast iron in desalination systems of saltwater. Polyvinyl alcohol/polyaniline/carboxylated graphene oxide nanocomposite was spin-coated onto cast iron samples. Electrochemical impedance spectroscopy (EIS) and electrochemical DC corrosion testing with a three-electrode system were used to study corrosion resistance in uncoated and coated cast iron samples. The results exhibit effective corrosion protection properties. The EIS data indicated better capacitance and higher impedance values for coated samples than bare metal, depicting enhanced corrosion resistance against the saline environment. Tafel analysis confirmed a significant decrease in the corrosion rate of the PVA/PANI/GO-COOH coated sample.

9.
Braz. J. Pharm. Sci. (Online) ; 58: e20110, 2022. graf
Artigo em Inglês | LILACS | ID: biblio-1403700

RESUMO

Abstract Molecular mechanisms involved in the development of muscle pain induced by static contraction are not completely elucidated. This study aimed to evaluate the involvement of the transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1) receptors expressed in peripheral and central terminals of primary afferents projected to gastrocnemius muscle and spinal cord in muscle pain induced by static contraction. An electrical stimulator provided the contraction of rat gastrocnemius muscle and mechanical muscle hyperalgesia was quantified through the pressure analgesimeter Randall-Selitto. AMG9810 and HC030031 were used. When administered in ipsilateral, but not contralateral gastrocnemius muscle, drugs prevented mechanical muscle hyperalgesia induced by static contraction. Similar results were obtained by intrathecal administrations. We propose that, in an inflammatory muscle pain, peripheral and central TRPV1 and TRPA1 work together to sensitize nociceptive afferent fibers, and that TRPV1 and TRPA1 receptors are potential target to control inflammatory muscle pain.


Assuntos
Animais , Masculino , Ratos , Anquirinas , Mialgia/induzido quimicamente , Medula Espinal/anormalidades , Preparações Farmacêuticas/administração & dosagem , Músculo Esquelético/lesões
10.
Distúrb. comun ; 33(4): 686-694, dez.2021. tab, ilus
Artigo em Português | LILACS | ID: biblio-1414195

RESUMO

Introdução: O nascimento de um filho com deficiência pode alterar rotinas e influenciar no processo de adaptação dos pais, por se caracterizar como um acontecimento não esperado. Ainda pode produzir nos progenitores sentimentos semelhantes aos vivenciados em um processo de luto. Objetivo: Analisar a relação entre a adaptação parental à filha com cegueira congênita e disfagia, relacionadas à prematuridade extrema, e seu possível impacto no processo de adesão às orientações terapêuticas sobre a alimentação da criança. Método: Trata-se de um estudo de caso de cunho qualitativo. Foi realizada uma análise da adaptação parental à deficiência, e avaliações fonoaudiológicas da linguagem e da disfagia. Resultados: A avaliação fonoaudiológica evidenciou disfagia para líquidos finos e ausência de alterações de linguagem. A restrição alimentar tornou-se evidente a partir da dificuldade parental em aceitar e seguir as orientações quanto à consistência alimentar. A análise dos dados de adaptação parental à deficiência da filha sugere que essa dificuldade esteve relacionada à aceitação da cegueira e da disfagia. A emergência de restrição alimentar esteve relacionada às dificuldades na aceitação das orientações fonoaudiológicas por parte dos pais, considerando a disfagia para líquidos finos. Essas dificuldades encontram um correlato na análise da adaptação parental do pai e da mãe. Conclusão: Evidencia-se a importância do acompanhamento por uma equipe interdisciplinar.


Introduction: The birth of a child with a disability can change routines and influence the parents' adaptation process, as it is characterized as an unexpected event. It can still produce similar feelings in parents as those experienced in a grieving process. Objective: To analyze the relationship between parental adaptation to the daughter with congenital blindness and dysphagia, related to extreme prematurity, and its possible impact on the process of adherence to therapeutic guidelines on child nutrition. Method: This is a qualitative case study. An analysis of parental adaptation to disability as well as language therapy assessments of language and dysphagia were performed. Results: The speech therapy evaluation showed dysphagia for fine liquids and absence of language disorders. Dietary restriction became evident from the parental difficulty in accepting and following the guidelines regarding food consistency. The analysis of the parental adaptation data to the daughter's disability suggests that this difficulty was related to the acceptance of blindness and dysphagia. The emergence of food restriction was related to the difficulties in parents' acceptance of speech therapy guidelines, considering dysphagia for thin liquids. These difficulties find a correlate in the analysis of the father and mother's parental adaptation. Conclusion: The importance of monitoring by an interdisciplinary team is evident.


Introducción: El nacimiento de un niño con discapacidad puede cambiar las rutinas y estilos de vida de los padres, ya que se caracteriza por ser un evento inesperado. Todavía puede producir sentimientos similares en los padres a los que experimentaron en un proceso de duelo. Objetivo: Analizar la relación entre la adaptación de los padres a la hija con ceguera congénita y disfagia, relacionada con la prematuridad extrema, y ​​su posible impacto en el proceso de adherencia a las guías terapéuticas en nutrición infantil. Método: Este es un estudio de caso cualitativo. Se realizó un análisis de la adaptación de los padres a la discapacidad y la evaluación del habla y el lenguaje de la disfagia. Resultados: La evaluación de logopedia mostró disfagia por líquidos finos y ausencia de trastornos del lenguaje. La restricción dietética se hizo evidente por la dificultad de los padres para aceptar y seguir las pautas con respecto a la consistencia de los alimentos. El análisis de los datos de adaptación de los padres a la discapacidad de la hija sugiere que esta dificultad estaba relacionada con la aceptación de la ceguera y la disfagia. La aparición de la restricción alimentaria se relacionó con las dificultades en la aceptación por parte de los padres de las pautas de logopedia, considerando la disfagia por líquidos diluidos. Estas dificultades encuentran correlación en el análisis de la adaptación parental del padre y la madre. Conclusión: Es evidente la importancia del seguimiento por parte de un equipo interdisciplinario.


Assuntos
Humanos , Feminino , Recém-Nascido , Pré-Escolar , Adaptação Psicológica , Transtornos de Deglutição , Cegueira/congênito , Dietoterapia , Pais/educação , Pais/psicologia , Equipe de Assistência ao Paciente , Recém-Nascido Prematuro , Pesquisa Qualitativa , Nutrição da Criança/educação
11.
Arq Neuropsiquiatr ; 79(8): 716-723, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34550184

RESUMO

BACKGROUND: Peripheral neural surgical decompression (PNSD) is used as a complementary therapy to the clinical treatment of neuritis to preserve neural function. OBJECTIVE: To evaluate the long-term (≥ 1 year) clinical and functional results for PNSD in leprosy neuritis. METHODS: This cross-sectional study included leprosy patients who were in late postoperative period (LPO) of surgical decompression of ulnar, median, tibial, and fibular nerves. Socioeconomic, epidemiological, and clinical data were collected. The following instruments were used in this evaluation: visual analogue pain scale (VAS), Douleur Neuropathique en 4 Questions (DN4), SALSA scale, and simplified neurological assessment protocol. The preoperative (PrO) and 180-day postoperative (PO180) results were compared. RESULTS: We evaluated 246 nerves from 90 patients: 56.6% were on multidrug therapy (MDT) and 43.3% discharged from MDT. Motor scores and pain intensity showed statistically significant improvement (p<0.01). There was an increase in sensory scores only for bilateral ulnar nerves (p<0.05). Of the operated cases, 26.0% of patients were referred for surgery of ulnar neuritis and 23.6% of tibial neuritis. Neuropathic pain was reported in 41% of cases. Daily dose of prednisone reduced from 39.6 mg (±3.0) in PrO, 16.3 mg (±5.2) in PO180, to 1.7 mg (±0.8) in LPO. The SALSA scale results showed mild activity limitation in 51% and moderate in 34% of patients. Eighty percent of individuals reported that the results reached their expectations. CONCLUSIONS: PNSD in leprosy was effective in the long term to decrease the prevalence and intensity of pain, improve motor function, and reduce the dose of corticosteroids, which is reflected in the patients' satisfaction.


Assuntos
Hansenostáticos , Hanseníase , Estudos Transversais , Descompressão , Quimioterapia Combinada , Seguimentos , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/complicações , Hanseníase/tratamento farmacológico
12.
Arq. neuropsiquiatr ; 79(8): 716-723, Aug. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1339224

RESUMO

ABSTRACT Background: Peripheral neural surgical decompression (PNSD) is used as a complementary therapy to the clinical treatment of neuritis to preserve neural function. Objective: To evaluate the long-term (≥ 1 year) clinical and functional results for PNSD in leprosy neuritis. Methods: This cross-sectional study included leprosy patients who were in late postoperative period (LPO) of surgical decompression of ulnar, median, tibial, and fibular nerves. Socioeconomic, epidemiological, and clinical data were collected. The following instruments were used in this evaluation: visual analogue pain scale (VAS), Douleur Neuropathique en 4 Questions (DN4), SALSA scale, and simplified neurological assessment protocol. The preoperative (PrO) and 180-day postoperative (PO180) results were compared. Results: We evaluated 246 nerves from 90 patients: 56.6% were on multidrug therapy (MDT) and 43.3% discharged from MDT. Motor scores and pain intensity showed statistically significant improvement (p<0.01). There was an increase in sensory scores only for bilateral ulnar nerves (p<0.05). Of the operated cases, 26.0% of patients were referred for surgery of ulnar neuritis and 23.6% of tibial neuritis. Neuropathic pain was reported in 41% of cases. Daily dose of prednisone reduced from 39.6 mg (±3.0) in PrO, 16.3 mg (±5.2) in PO180, to 1.7 mg (±0.8) in LPO. The SALSA scale results showed mild activity limitation in 51% and moderate in 34% of patients. Eighty percent of individuals reported that the results reached their expectations. Conclusions: PNSD in leprosy was effective in the long term to decrease the prevalence and intensity of pain, improve motor function, and reduce the dose of corticosteroids, which is reflected in the patients' satisfaction.


RESUMO Antecedentes: A descompressão cirúrgica neural periférica (DCNP) é usada como uma terapia complementar ao tratamento clínico da neurite hansênica para preservar a função neural. Objetivo: Avaliar a longo prazo (≥ 1 ano) os resultados clínicos e funcionais da DCNP na neurite hansênica. Métodos: Este estudo transversal incluiu pacientes que estavam no pós-operatório tardio (POT) de cirurgia de descompressão dos nervos ulnares, medianos, tibiais e fibulares. Foram coletados dados socioeconômicos, epidemiológicos e clínicos. Os instrumentos utilizados foram: escala visual analógica de dor (EVA), questionário de dor neuropática 4 (DN4), escala SALSA e protocolo de avaliação neurológica simplificada. Os resultados obtidos foram comparados com os do pré-operatório (PrO) e pós-operatório de 180 dias (PO180). Resultados: Foram avaliados 246 nervos de 90 pacientes: 56,6% estavam em poliquimioterapia (PQT) e 43,3% em alta da PQT. Escores motores e intensidade da dor apresentaram melhora significante (p<0,01). Houve aumento nos escores sensitivos nos nervos ulnares bilaterais (p<0,05). Neurite ulnar foi indicação cirúrgica em 26,0% dos casos operados, seguida pela neurite tibial (23,6%). Dor neuropática foi relatada em 41% dos casos. Dose diária de prednisona reduziu de 39,6 mg (±3,0) na PrO, 16,3 mg (±5,2) na PO180, para 1,7 mg (±0,8) na POT. Escala SALSA mostrou limitação leve da atividade em 51% e moderada em 34% dos pacientes. 80% dos indivíduos relataram que os resultados atingiram suas expectativas. Conclusão: DCNP na hanseníase foi eficaz a longo prazo na redução da prevalência e intensidade da dor, na melhora da função motora e redução da dose de corticosteroides, refletindo na satisfação do paciente.


Assuntos
Humanos , Hansenostáticos/uso terapêutico , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Estudos Transversais , Seguimentos , Descompressão , Quimioterapia Combinada
13.
Dement. neuropsychol ; 15(2): 291-293, Apr.-June 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1286198

RESUMO

ABSTRACT. Brain-damaged patients can develop abnormal attitudes towards their deficits. Misoplegia is one such example, involving exaggerated aversion to an impaired limb, sometimes associated with hatred of paresis and verbal or physical abuse directed at the paretic limb. Few studies or reports on this disorder are available in the literature, prompting the present case report of a patient with misoplegia and vascular dementia.


RESUMO. Pacientes com lesões cerebrais podem apresentar atitudes anormais em relação a seus déficits. Um exemplo é a misoplegia, uma aversão excessiva em relação ao membro com déficit, podendo estar associado a ódio à paralisia e maus tratos verbais ou físicos contra os membros paralisados. Ainda há poucos estudos e relatos sobre esse distúrbio na literatura, evidenciando a importância de um relato de caso de um paciente portador de misoplegia e demência vascular.


Assuntos
Humanos , Demência , Comportamento Autodestrutivo , Doenças Neurodegenerativas , Transtornos Mentais
15.
Biofabrication ; 13(3)2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33592595

RESUMO

Three-dimensional (3D) cell culture has tremendous advantages to closely mimic thein vivoarchitecture and microenvironment of healthy tissue and organs, as well as of solid tumors. Spheroids are currently the most attractive 3D model to produce uniform reproducible cell structures as well as a potential basis for engineering large tissues and complex organs. In this review we discuss, from an engineering perspective, processes to obtain uniform 3D cell spheroids, comparing dynamic and static cultures and considering aspects such as mass transfer and shear stress. In addition, computational and mathematical modeling of complex cell spheroid systems are discussed. The non-cell-adhesive hydrogel-based method and dynamic cell culture in bioreactors are focused in detail and the myriad of developed spheroid characterization techniques is presented. The main bottlenecks and weaknesses are discussed, especially regarding the analysis of morphological parameters, cell quantification and viability, gene expression profiles, metabolic behavior and high-content analysis. Finally, a vast set of applications of spheroids as tools forin vitrostudy model systems is examined, including drug screening, tissue formation, pathologies development, tissue engineering and biofabrication, 3D bioprinting and microfluidics, together with their use in high-throughput platforms.


Assuntos
Bioimpressão , Esferoides Celulares , Técnicas de Cultura de Células , Hidrogéis , Engenharia Tecidual
16.
Bone ; 145: 115842, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33422700

RESUMO

OBJECTIVES: This study aimed to evaluate the involvement of Angiotensin II (Ang II) in joint lesions associated with osteoarthritis (OA) in vitro and in vivo. METHODS: Chondrocyte cultures were obtained from knee joints of neonatal rats and stimulated with Ang II/MIA/ACE inhibitors. In vivo, rats treated or not with the ACE inhibitor captopril, received daily injections of Ang II or sodium monoiodoacetate (MIA) in knee joints for evaluation of cartilage, bone, and synovial lesions. RESULTS: Cultured chondrocytes expressed the mRNA for Ace, Agtr1, Agtr2, and Mas1. Stimulating cells with Ang II reduced chondrocyte viability and metabolism. Accordingly, in vivo Ang II injection into the knees of rats triggered hyperalgesia, joint edema, increased the number of leukocytes in the joint cavity, and induced cartilage lesions associated with OA alterations. In further experiments, Ang II synthesis was prevented with the ACE inhibitor Captopril in the context of MIA-induced OA. Ang II inhibition with captopril improved the OARSI score, induced chondroprotection, and reduced the leukocyte recruitment from synovium after MIA. Additionally, captopril prevented MIA-induced bone resorption, by decreasing the number of osteoclasts and increasing the expression of IL-10 in the bone. In vitro, inhibiting Ang II synthesis decreased MIA-induced chondrocyte death and increased Col2a1 transcription. CONCLUSION: Ang II induces chondrocyte death and joint tissue damages associated with OA and its modulation can be a therapeutic strategy in osteoarthritis.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Osteoartrite , Angiotensina II , Animais , Condrócitos , Articulação do Joelho , Osteoartrite/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Proto-Oncogene Mas , Ratos
17.
Mult Scler Relat Disord ; 47: 102643, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310420

RESUMO

Elsberg syndrome (ES) refers to the combination of myelitis and lumbosacral radiculitis associated with infection caused by the virus of the Herpesviridae family. We present a case of a 52-year-old man with a 9 months diagnosis of Crohn's disease, in use of infliximab with good disease control, complaining of 2 months history of progressive urinary retention and loss of sensation of the genital and left lower limb regions associated with varicella zoster virus (VZV) infection and recent HIV diagnosis.


Assuntos
Varicela , Doença de Crohn , Infecções por HIV , Herpes Zoster , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Humanos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade
19.
BMJ Case Rep ; 13(12)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298487

RESUMO

Solid pseudopapillary neoplasms (SPNs) are rare pancreatic cystic neoplasms occurring predominantly in young women and diagnosis is often a challenge. This report describes the case of a 23-year-old primigravida who presented with abnormally elevated liver blood tests at 24 weeks of gestation. Imaging studies were suggestive of SPN with metastatic liver disease. A multidisciplinary team approach decided on a preterm caesarean delivery of a healthy female child at 36 weeks of gestation. Subsequently, a CT-guided biopsy was performed, with confirmation of SPN in the anatomopathological study. Subpartial pancreatectomy, partial gastrectomy, cholecystectomy, total splenectomy and partial hepatectomy were successfully performed. A 3-month control CT scan and positron emission tomography-CT studies revealed disease recurrence with pulmonary and liver metastatic disease. The patient was started on a palliative chemotherapy protocol with good tolerance. To our knowledge this is the first case of a SPN described in pregnancy with distant metastasis and disseminated recurrence after surgical treatment.


Assuntos
Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Diagnóstico Pré-Natal , Carcinoma Papilar/patologia , Cesárea , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Imageamento por Ressonância Magnética , Pancreatectomia , Neoplasias Pancreáticas/patologia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/cirurgia , Esplenectomia , Tomografia Computadorizada por Raios X , Adulto Jovem
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