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1.
Braz. j. med. biol. res ; 55: e12038, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1384137

RESUMO

The aim of this study was to review the symptomatic manifestations of COVID-19 in children in the scientific literature. An integrative review of studies published between December 2019 and September 5, 2021, from the Medical Literature Analysis and Retrieval System Online, Web of Science, Scopus, Literatura Latino-Americana em Ciência de Saúde, and Base de Dados de Enfermagem databases, was carried out to answer the following research question: What symptomatic manifestations does COVID-19 cause in children?". Twenty articles were included. The main symptoms described were fever, cough, diarrhea, vomiting, sore throat, dyspnea, headache, abdominal pain, malaise, and weakness or tiredness. The findings of this review can contribute to the diagnosis and clinical decision-making of the health team by providing information that facilitates the identification of COVID-19 in the target population, favoring early identification, better care, and consequently a better prognosis.

2.
Toxicon ; 200: 38-47, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34237340

RESUMO

Induction of CD8+ T cell responses against tumor cells and intracellular pathogens is an important goal of modern vaccinology. One approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFPs), such as Listeriolysin O (LLO), which has shown efficacy at priming strong and sustained CD8+ T cell responses. Recently, we have demonstrated that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, co-encapsulated into liposomes with ovalbumin (OVA) was able to stimulate, antigen presenting cells, antigen-specific CD8+ T cells and anti-tumor activity in mice. In the present study, we aimed to compare StII and LLO in terms of their abilities to stimulate dendritic cells and to induce major histocompatibility complex (MHC) class I restricted T cell responses against OVA. Interestingly, StII exhibited similar abilities to LLO in vitro of inducing dendritic cells maturation, as measured by increased expression of CD40, CD80, CD86 and MHC-class II molecules, and of stimulating OVA cross-presentation to a CD8+ T cell line. Remarkably, using an ex vivo Enzyme-Linked ImmunoSpot Assay (ELISPOT) to monitor gamma interferon (INF-γ) producing effector memory CD8+ T cells, liposomal formulations containing either StII or LLO induced comparable frequencies of OVA-specific INF-γ producing CD8+ T cells in mice that were sustained in time. However, StII-containing liposomes stimulated antigen-specific memory CD8+ T cells with a higher potential to secrete IFN-γ than liposomes encapsulating LLO. This StII immunostimulatory property further supports its use for the rational design of T cell vaccines against cancers and intracellular pathogens. In summary, this study indicates that StII has immunostimulatory properties similar to LLO, despite being evolutionarily distant PFPs.


Assuntos
Linfócitos T CD8-Positivos , Linfócitos T Citotóxicos , Animais , Toxinas Bacterianas , Venenos de Cnidários , Células Dendríticas , Proteínas de Choque Térmico , Proteínas Hemolisinas , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina
3.
Bioelectrochemistry ; 141: 107867, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34118553

RESUMO

During fermentation in Escherichia coli succinate is transported via Dcu transporters, encoded dcuA, dcuB, dcuC and dcuD although the role of DcuD protein has not been elucidated yet. It has been shown contribution of Dcu transporters in the N,N'-dicyclohexylcarbodiimide (DCCD) sensitive proton and potassium transport through the cytoplasmic membrane and membrane-associated ATPase activity. Total H± efflux was decreased ~ 40% while K± uptake was absent in dcuD mutant. DCCD-sensitive H± flux was absent in dcuD nevertheless it was increased ~ 3 fold in dcuACB. K± uptake in dcuACB was stimulated ~ 30% compared to wild type but in DCCD assays K± ions were effluxed with the rate of 0.15 mmol/min per 109 cells/ml. In dcuACB mutant membrane potential (ΔΨ) was ~ 30 mV higher than in wild type. dcuD gene expression was increased in the dcuACB mutant respect to wild type at pH 7.5 (~120%), suggesting that an increment of DcuD activity compensates the lack of DcuA, DcuC and DcuB carriers. It can be concluded that active DcuD is important for H± efflux via the FOF1-ATPase and K± uptake at pH 7.5. In addition, DcuA, DcuB and DcuC transporters are crucial for regulating DCCD-sensitive K± transport and ΔΨ in E. coli.


Assuntos
Transportadores de Ácidos Dicarboxílicos/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Fermentação , Glucose/metabolismo , Concentração de Íons de Hidrogênio , ATPases Translocadoras de Prótons/metabolismo , Potenciais da Membrana , Prótons
4.
Arts Health ; 13(2): 189-203, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32223531

RESUMO

Background: The therapeutic role of humor and hospital clowns has become a focus of interest in recent decades. Most of the research in the area has focused on children; here, we explore the influence of clown performances on adult cancer patients, their companions, and health-care staff.Methods: Ninety-nine cancer patients and 113 companions were assessed pre- and post-interventions performed by professional clowns; 31 health professionals were asked about the possible influence of the presence of clowns in hospital on their work.Results: Patients felt that clowning performances helped to reduce their level of psychological symptoms, but not their physical symptoms. Companions reported improvements in all the psychological symptoms explored. Health professionals reported that the presence of clowns in the workplace improved their well-being.Conclusions: Clowning performances helped to improve psychological functioning in all the populations studied, especially in companions. Adult hospitals should consider promoting clowning interventions to improve general well-being.


Assuntos
Hospitais , Neoplasias , Adulto , Criança , Atenção à Saúde , Pessoal de Saúde , Humanos
6.
Bone Joint J ; 101-B(7_Supple_C): 98-103, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31256646

RESUMO

AIMS: The aim of this study was to determine the general postoperative opioid consumption and rate of appropriate disposal of excess opioid prescriptions in patients undergoing primary unilateral total knee arthroplasty (TKA). PATIENTS AND METHODS: In total, 112 patients undergoing surgery with one of eight arthroplasty surgeons at a single specialty hospital were prospectively enrolled. Three patients were excluded for undergoing secondary procedures within six weeks. Daily pain levels and opioid consumption, quantity, and disposal patterns for leftover medications were collected for six weeks following surgery using a text-messaging platform. RESULTS: Overall, 103 of 109 patients (94.5%) completed the daily short message service (SMS) surveys. The mean oral morphine equivalents (OME) consumed during the six weeks post-surgery were 639.6 mg (sd 323.7; 20 to 1616) corresponding to 85.3 tablets of 5 mg oxycodone per patient. A total of 66 patients (64.1%) had stopped taking opioids within six weeks of surgery and had the mean equivalent of 18 oxycodone 5 mg tablets remaining. Only 17 patients (25.7%) appropriately disposed of leftover medications. CONCLUSION: These prospectively collected data provide a benchmark for general opioid consumption after uncomplicated primary unilateral TKA. Many patients are prescribed more opioids than they require, and leftover medication is infrequently disposed of appropriately, which increases the risk for illicit diversion. Cite this article: Bone Joint J 2019;101-B(7 Supple C):98-103.


Assuntos
Analgésicos Opioides/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Padrões de Prática Médica , Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos/epidemiologia
7.
Sci Rep ; 9(1): 4279, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30862913

RESUMO

During fermentation Escherichia coli excrete succinate mainly via Dcu family carriers. Current work reveals the total and N,N'-dicyclohexylcarbodiimide (DCCD) inhibited ATPase activity at pH 7.5 and 5.5 in E. coli wild type and dcu mutants upon glycerol fermentation. The overall ATPase activity was highest at pH 7.5 in dcuABCD mutant. In wild type cells 50% of the activity came from the FOF1-ATPase but in dcuD mutant it reached ~80%. K+ (100 mM) stimulate total but not DCCD inhibited ATPase activity 40% and 20% in wild type and dcuD mutant, respectively. 90% of overall ATPase activity was inhibited by DCCD at pH 5.5 only in dcuABC mutant. At pH 7.5 the H+ fluxes in E. coli wild type, dcuD and dcuABCD mutants was similar but in dcuABC triple mutant the H+ flux decreased 1.4 fold reaching 1.15 mM/min when glycerol was supplemented. In succinate assays the H+ flux was higher in the strains where DcuD is absent. No significant differences were determined in wild type and mutants specific growth rate except dcuD strain. Taken together it is suggested that during glycerol fermentation DcuD has impact on H+ fluxes, FOF1-ATPase activity and depends on potassium ions.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Glicerol/metabolismo , Adenosina Trifosfatases/genética , Transportadores de Ácidos Dicarboxílicos/genética , Transportadores de Ácidos Dicarboxílicos/metabolismo , Dicicloexilcarbodi-Imida/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Fermentação/efeitos dos fármacos , Fermentação/genética , Fermentação/fisiologia , Concentração de Íons de Hidrogênio
9.
J Surg Case Rep ; 2018(10): rjy261, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30310647

RESUMO

Metastases from renal clear cell carcinoma (RCCC) to the head and neck (HN) region are rare, representing 8-14% of all RCCC metastases, with the thyroid gland being the most common site of RCCC metastasis in the HN. Metastatic tumors that are located in the salivary glands have a prevalence of 5%, while the submandibular gland is only involved in 1% of the cases. We present the case of a 74-year-old female patient with metastasis to the submandibular gland, 11 years after radical nephrectomy for a RCCC.

10.
Actas Urol Esp (Engl Ed) ; 42(7): 425-434, 2018 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29029769

RESUMO

INTRODUCTION: Muscle-invasive bladder malignancies represent 20-30% of all bladder cancers. These patients require imaging tests to determine the regional and distant staging. OBJECTIVE: To describe the role of various imaging tests in the diagnosis, staging and follow-up of muscle-invasive bladder cancer. To assess recent developments in radiology aimed at improving the sensitivity and specificity of local staging and treatment response. ACQUISITION OF EVIDENCE: We conducted an updated literature review. SYNTHESIS OF THE EVIDENCE: Computed tomography and magnetic resonance imaging (MRI) are the tests of choice for performing proper staging prior to surgery. Computed tomography urography is currently the most widely used technique, although it has limitations in local staging. Ultrasonography still has a limited role. Recent developments in MRI have improved its capacity for local staging. MRI has been suggested as the test of choice for the follow-up, with promising results in assessing treatment response. Positron emission tomography could improve the detection of adenopathies and extrapelvic metastatic disease. CONCLUSIONS: Imaging tests are essential for the diagnosis, staging and follow-up of muscle-invasive bladder cancer. Recent technical developments represent important improvements in local staging and have opened the possibility of assessing treatment response.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Carcinoma/patologia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Músculo Liso , Invasividade Neoplásica , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/patologia
11.
Bone Joint J ; 99-B(1 Supple A): 25-30, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28042115

RESUMO

This review summarises the technique of impaction grafting with mesh augmentation for the treatment of uncontained acetabular defects in revision hip arthroplasty. The ideal acetabular revision should restore bone stock, use a small socket in the near-anatomic position, and provide durable fixation. Impaction bone grafting, which has been in use for over 40 years, offers the ability to achieve these goals in uncontained defects. The precepts of modern, revision impaction grafting are that the segmental or cavitary defects must be supported with a mesh; the contained cavity is filled with vigorously impacted morselised fresh-frozen allograft; and finally, acrylic cement is used to stabilise the graft and provide rigid, long-lasting fixation of the revised acetabular component. Favourable results have been published with this technique. While having its limitations, it is a viable option to address large acetabular defects in revision arthroplasty. Cite this article: Bone Joint J 2017;99-B(1 Supple A):25-30.


Assuntos
Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Transplante Ósseo/métodos , Prótese de Quadril , Telas Cirúrgicas , Acetábulo/cirurgia , Cimentos Ósseos , Articulação do Quadril/diagnóstico por imagem , Humanos , Polietileno , Cuidados Pré-Operatórios/métodos , Desenho de Prótese , Falha de Prótese , Radiografia , Reoperação/instrumentação , Reoperação/métodos
12.
BMJ Support Palliat Care ; 7(2): 164-172, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26182947

RESUMO

BACKGROUND: This study analysed the impact on palliative care outcomes of a new specialist palliative care service for patients severely affected by amyotrophic lateral sclerosis (ALS/MND), multiple sclerosis, Parkinson's disease and related disorders (multiple system atrophy progressive supranuclear palsy, MSA-PSP). METHODS: The design followed the Medical Research Council Framework for the evaluation of complex interventions. A phase II randomised controlled trial (RCT) was undertaken comparing an immediate referral to the service (FT, fast track) to a 16-week wait (standard track (ST), standard best practice) using a parallel arm design. The main outcome measures were Quality of Life (measured with Schedule for the Evaluation of Individual Quality of Life Direct Weight, SEIQoL-DW) and burden of the carers (Caregivers Burden Inventory, CBI), with secondary outcomes of symptoms, psychosocial and spiritual issues. RESULTS: 50 patients severely affected by neurodegenerative conditions and their informal family carers were randomised: 25 FT, 25 ST. At baseline (T0), there were no differences between groups. 4 patients died during the follow-up (2 FT, 2 ST) and 2 FT patients dropped out before the end of the study. After 16 weeks (T1), FT participants scored significant improvement in the SEIQoL-DW index, pain dyspnoea sleep disturbance and bowel symptoms. CONCLUSIONS: This exploratory RCT provides evidence that no harm was experienced by SPCS for patients severely affected by neurodegenerative disorders. There was an improvement in quality of life and physical symptoms for neurological patients in palliative care. Caregiver burden was not affected by the service.


Assuntos
Doenças Neurodegenerativas/psicologia , Qualidade de Vida , Adulto , Idoso , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Projetos Piloto , Resultado do Tratamento
13.
J Arthroplasty ; 32(1): 183-188, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27480825

RESUMO

BACKGROUND: Extensor mechanism disruption remains a devastating complication after total knee arthroplasty. The purpose of this study is to describe the outcomes of extensor mechanism allograft (EMA) reconstruction in a large single-center case series. METHODS: Consecutive patients with a previous total knee arthroplasty undergoing extensor mechanism reconstruction using a fresh-frozen EMA tensioned in full extension were identified retrospectively from single-center institutional database (N = 25 patients, 26 knees; mean follow-up 68 months [range 22-113 months]). The primary outcome was initial allograft failure, defined as removal of the allograft or extensor lag >30 degrees at most recent follow-up. RESULTS: Sixty-nine percent (18/26) of knees had retained their initial allograft reconstruction at their latest follow-up despite reoperation rates of 58% (15/26). A younger age was significantly associated with failure of the initial allograft reconstruction. Knee Society Scores increased from 101 (38 standard deviation [SD]) to 116 (40 SD) at most recent follow-up for the group as a whole (P = .4). Patients undergoing a reoperation for any cause had lower Knee Society Scores (101 [SD 38] vs 138 [SD 32], respectively; P = .04) at most recent follow-up. CONCLUSION: EMA reconstruction shows adequate overall intermediate-term survival; however, reoperation rates were high and associated with worse functional outcomes.


Assuntos
Aloenxertos/estatística & dados numéricos , Artroplastia do Joelho/efeitos adversos , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
15.
Bone Joint J ; 98-B(1 Suppl A): 54-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26733642

RESUMO

We describe our technique and rationale using hybrid fixation for primary total hip arthroplasty (THA) at the Hospital for Special Surgery. Modern uncemented acetabular components have few screw holes, or no holes, polished inner surfaces, improved locking mechanisms, and maximised thickness and shell-liner conformity. Uncemented sockets can be combined with highly cross-linked polyethylene liners, which have demonstrated very low wear and osteolysis rates after ten to 15 years of implantation. The results of cement fixation with a smooth or polished surface finished stem have been excellent, virtually eliminating complications seen with cementless fixation like peri-operative femoral fractures and thigh pain. Although mid-term results of modern cementless stems are encouraging, the long-term data do not show reduced revision rates for cementless stems compared with cemented smooth stems. In this paper we review the conduct of a hybrid THA, with emphasis on pre-operative planning, surgical technique, hypotensive epidural anaesthesia, and intra-operative physiology.


Assuntos
Artroplastia de Quadril/métodos , Prótese de Quadril , Osteoartrite do Quadril/cirurgia , Hospitais , Humanos , Cuidados Intraoperatórios , Cuidados Pré-Operatórios , Desenho de Prótese , Ajuste de Prótese
16.
Drugs ; 76(3): 315-30, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26755179

RESUMO

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.


Assuntos
Analgésicos Opioides , Dor Irruptiva , Neoplasias/tratamento farmacológico , Manejo da Dor/métodos , Medição da Dor/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Dor Irruptiva/diagnóstico , Dor Irruptiva/tratamento farmacológico , Humanos , Adesão à Medicação , Guias de Prática Clínica como Assunto , Qualidade de Vida , Inquéritos e Questionários
17.
Ann Ig ; 27(5): 711-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26661912

RESUMO

BACKGROUND: Literature reports an incidence of surgical site infections (SSIs) in oncological patients undergoing prosthetic replacement between 8% and 35% after first implantation and 43% after revision. The purpose of this retrospective study, conducted at the oncologic orthopaedic unit of G. Pini Orthopaedic Hospital in Milan, was to evaluate: - number of SSIs in oncological megaprosthetic reconstruction between 2008 and 2011, - possible risk factors associated with the onset of SSIs, - antibiotic prophylaxis applied. DESIGN AND METHODS: We reviewed medical records of patients who underwent megaprosthetic reconstruction and collected data on whole treatment and follow up after discharge, focusing on possible risk factors implied in the onset of SSIs such as patient characteristics, site of surgery, duration of surgery, number of persons in the operating room, size of resection, antibiotic prophylaxis. We recorded every SSI which met the criteria set by the Hospital in Europe Link for Infection Control through Surveillance (HELICS) protocol. RESULTS: One-hundred and eleven surgeries were evaluated. Administration of prophylaxis was generally recorded and continued postoperatively for an average of 18.89 days, often depending on the length of the post-surgical stay. Mean duration of surgery was 254 minutes with an average of 7 persons attending the operating room. We recorded 6 SSIs.


Assuntos
Neoplasias Ósseas/cirurgia , Procedimentos Ortopédicos/métodos , Implantação de Prótese/métodos , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Antibioticoprofilaxia/métodos , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/prevenção & controle
19.
Endocrinology ; 156(11): 4081-93, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26327577

RESUMO

Osteoporosis is a metabolic bone disease associated with unequilibrated bone remodeling resulting from decreased bone formation and/or increased bone resorption, leading to progressive bone loss. In osteoporotic patients, low bone mass is associated with an increase of bone marrow fat resulting from accumulation of adipocytes within the bone marrow. Marrow adipocytes are active secretory cells, releasing cytokines, adipokines and free fatty acids (FA) that influence the bone marrow microenvironment and alter the biology of neighboring cells. Therefore, we examined the effect of palmitate (Palm) and oleate (Ole), 2 highly prevalent FA in human organism and diet, on the function and survival of human mesenchymal stem cells (MSC) and MSC-derived osteoblastic cells. The saturated FA Palm exerted a cytotoxic action via initiation of endoplasmic reticulum stress and activation of the nuclear factor κB (NF-κB) and ERK pathways. In addition, Palm induced a proinflammatory response, as determined by the up-regulation of Toll-like receptor 4 expression as well as the increase of IL-6 and IL-8 expression and secretion. Moreover, we showed that MSC-derived osteoblastic cells were more sensitive to lipotoxicity than undifferentiated MSC. The monounsaturated FA Ole fully neutralized Palm-induced lipotoxicity by impairing activation of the pathways triggered by the saturated FA. Moreover, Ole promoted Palm detoxification by fostering its esterification into triglycerides and storage in lipid droplets. Altogether, our data showed that physiological concentrations of Palm and Ole differently modulated cell death and function in bone cells. We therefore propose that FA could influence skeletal health.


Assuntos
Mediadores da Inflamação/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Ácido Oleico/farmacologia , Osteoblastos/efeitos dos fármacos , Palmitatos/farmacologia , Adolescente , Adulto , Western Blotting , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Adulto Jovem
20.
Stem Cell Rev Rep ; 11(6): 841-51, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26254594

RESUMO

Human bone marrow-derived mesenchymal stem cells (hBMSC) are able to differentiate into cells of connective tissue lineages, including bone and cartilage. They are therefore considered as a promising tool for the treatment of bone degenerative diseases. One of the major issues in regenerative cell therapy is the biosafety of fetal bovine serum used for cell culture. Therefore, the development of a culture medium devoid of serum but preserving hBMSC viability will be of clinical value. The glucose-dependent insulinotropic peptide (GIP) has an anti-apoptotic action in insulin-producing cells. Interestingly, GIP also exerts beneficial effects on bone turnover by acting on osteoblasts and osteoclasts. We therefore evaluated the ability of GIP to prevent cell death in osteoblastic cells cultured in serum-free conditions. In hBMSC and SaOS-2 cells, activation of the GIP receptor increased intracellular cAMP levels. Serum deprivation induced apoptosis in SaOS-2 and hBMSC that was reduced by 30 and 50 %, respectively, in the presence of GIP. The protective effect of GIP involves activation of the adenylate cyclase pathway and inhibition of caspases 3/7 activation. These findings demonstrate that GIP exerts a protective action against apoptosis in hBMSC and suggest a novel approach to preserve viability of hBMSC cultured in the absence of serum.


Assuntos
Apoptose/efeitos dos fármacos , Meios de Cultura Livres de Soro/farmacologia , Polipeptídeo Inibidor Gástrico/farmacologia , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Receptores dos Hormônios Gastrointestinais/metabolismo , Células da Medula Óssea/citologia , Caspase 3/metabolismo , Caspase 7/metabolismo , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/metabolismo , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo
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