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1.
Stem Cells Transl Med ; 9(2): 221-234, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31774626

RESUMO

Bronchopulmonary dysplasia (BPD) is a devastating lung condition that develops in premature newborns exposed to prolonged mechanical ventilation and supplemental oxygen. Significant morbidity and mortality are associated with this costly disease and effective therapies are limited. Mesenchymal stem/stromal cells (MSCs) are multipotent cells that can repair injured tissue by secreting paracrine factors known to restore the function and integrity of injured lung epithelium and endothelium. Most preclinical studies showing therapeutic efficacy of MSCs for BPD are administered either intratracheally or intravenously. The purpose of this study was to examine the feasibility and effectiveness of human cord tissue-derived MSC administration given via the intranasal route. Human umbilical cord tissue MSCs were isolated, characterized, and given intranasally (500 000 cells per 20 µL) to a hyperoxia-induced rat model of BPD. Lung alveolarization, vascularization, and pulmonary vascular remodeling were restored in animals receiving MSC treatment. Gene and protein analysis suggest the beneficial effects of MSCs were attributed, in part, to a concerted effort targeting angiogenesis, immunomodulation, wound healing, and cell survival. These findings are clinically significant, as neonates who develop BPD have altered alveolar development, decreased pulmonary vascularization and chronic inflammation, all resulting in impaired tissue healing. Our study is the first to report the intranasal delivery of umbilical cord Wharton's jelly MSCs in experimental BPD is feasible, noninvasive, and an effective route that may bear clinical applicability.

2.
Respir Res ; 20(1): 239, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666086

RESUMO

BACKGROUND: Inflammation plays an important role in the pathogenesis of many lung diseases. Preclinical studies suggest that mesenchymal stromal cell (MSC) conditioned media (CdM) can attenuate inflammation. Our aim was threefold: (1) summarize the existing animal literature evaluating CdM as a therapeutic agent for pediatric/adult lung disease, (2) quantify the effects of CdM on inflammation, and (3) compare inflammatory effects of CdM to MSCs. METHODS: Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed in five databases. Meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD). RESULTS: A total of 10 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, and acute respiratory distress syndrome. CdM decreased inflammatory cells (1.02 SMD, 95% CI 0.86, 1.18) and cytokines (0.71 SMD, 95% CI 0.59, 0.84). The strongest effect for inflammatory cells was in bronchopulmonary dysplasia (3.74 SMD, 95% CI 3.13, 4.36) while pulmonary hypertension had the greatest reduction in inflammatory cytokine expression (1.44 SMD, 95% CI 1.18, 1.71). Overall, CdM and MSCs had similar anti-inflammatory effects. CONCLUSIONS: In this meta-analysis of animal models recapitulating lung disease, CdM improved inflammation and had an effect size comparable to MSCs. While these findings are encouraging, the risk of bias and heterogeneity limited the strength of our findings.

3.
Cochrane Database Syst Rev ; 9: CD013201, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549743

RESUMO

BACKGROUND: Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a substantial issue in neonatal intensive care units worldwide. Current therapies to prevent or treat GMH-IVH are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, and/or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies. OBJECTIVES: To determine the benefits and harms of stem cell-based interventions for prevention or treatment of germinal matrix-intraventricular haemorrhage (GM-IVH) in preterm infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1), in the Cochrane Library; MEDLINE via PubMed (1966 to 7 January 2019); Embase (1980 to 7 January 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 7 January 2019). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We attempted to identify randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing (1) stem cell-based interventions versus control; (2) mesenchymal stromal cells (MSCs) of type or source versus MSCs of other type or source; (3) stem cell-based interventions other than MSCs of type or source versus stem cell-based interventions other than MSCs of other type or source; or (4) MSCs versus stem cell-based interventions other than MSCs. For prevention studies, we included extremely preterm infants (less than 28 weeks' gestation), 24 hours of age or less, without ultrasound diagnosis of GM-IVH; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH. DATA COLLECTION AND ANALYSIS: For each of the included trials, two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs, other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). Primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, GM-IVH, and extension of pre-existing non-severe GM-IVH. We planned to use the GRADE approach to assess the quality of evidence. MAIN RESULTS: Our search strategy yielded 769 references. We did not find any completed studies for inclusion. One randomised controlled trial is currently registered and ongoing. Five phase 1 trials are described in the excluded studies. AUTHORS' CONCLUSIONS: Currently no evidence is available to show the benefits or harms of stem cell-based interventions for treatment or prevention of GM-IVH in preterm infants.


Assuntos
Hemorragia Cerebral/prevenção & controle , Circulação Cerebrovascular/fisiologia , Mortalidade Infantil , Lactente Extremamente Prematuro , Doenças do Prematuro/prevenção & controle , Células-Tronco , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Prematuro/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Syst Rev ; 8(1): 126, 2019 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-31128597

RESUMO

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common form of hearing impairment and is characterized by a loss of receptor hair cells and/or spiral ganglion neurons. Regenerative stem cell therapy could potentially restore normal hearing and slow the progression of hearing loss in patients. Preclinical animal studies have demonstrated that mesenchymal stem cells (MSCs) could be a promising new therapy for this condition. These findings have prompted investigators to begin human clinical trials to assess the safety and efficacy of MSCs for the treatment of SNHL. The objective of the proposed systematic review is to examine the efficacy of MSCs as a therapy for SNHL in animal models. METHODS: We will include preclinical animal studies of SNHL in which MSCs are administered, and outcomes are compared against MSC-naïve controls. The primary outcome will include audiologic tests that are routinely used in experimental studies of hearing loss, such as auditory brainstem response (ABR) and distortion product otoacoustic emissions testing (DPOAE). Secondary outcomes will include histology, microscopy, gene protein expression, and behavioral responses of animals. Electronic searches of MEDLINE via PubMed, Scopus, ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be performed. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias and publication bias will be assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool and Funnel Plots/Egger's regression tests, respectively. DISCUSSION: This systematic review will provide a summary of the efficacy of MSC therapy in animal models of SNHL, utilizing functional hearing assessment as a primary outcome. Findings from this review are important because they can elucidate research gaps that should be addressed in future preclinical studies and in turn can be translated into clinical studies. SYSTEMATIC REVIEW REGISTRATION: CAMARADES ( http://www.dcn.ed.ac.uk/camarades/ ).

6.
BMC Cancer ; 19(1): 207, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845981

RESUMO

BACKGROUND: The role of eosinophils in cancer is not yet completely understood, but patients with eosinophilia show a trend towards longer survival in several types of cancer, including melanoma. However, eosinophil count at initial diagnosis of metastatic melanoma does not predict survival. Since eosinophil cationic protein (ECP) mediates anticancer effects, such as tissue remodelling and cytotoxic activity, we investigated this marker as an early prognostic marker in metastatic melanoma. METHODS: Serum of 56 melanoma patients was collected at the time of diagnosis of metastatic disease. ECP levels as measured by ELISA were correlated with overall survival (OS) in patients before systemic therapy with immunotherapy or chemotherapy. Statistical analyses were performed using the Log-Rank (Mantel-Cox) test. RESULTS: The median OS for patients with high serum ECP above 12.2 ng/ml was 12 months (n = 39), compared to 28 months for patients with ECP below this threshold (n = 17; p = 0.0642). In patients with cutaneous melanoma, excluding patients with uveal and mucosal melanoma, the survival difference was even more striking (p = 0.0393). ECP's effect size on OS was observed independently of the consecutive therapy. ECP levels were not correlated with LDH levels. CONCLUSION: ECP seems to be a novel prognostic serum marker for the outcome of melanoma patients, which is independent of LDH and easy to perform in clinical practice. The striking negative prognostic value of high ECP level is unanticipated and can guide patient management.


Assuntos
Biomarcadores Tumorais , Proteína Catiônica de Eosinófilo/sangue , Melanoma/sangue , Melanoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Terapia Combinada , Ensaio de Imunoadsorção Enzimática , Eosinofilia , Feminino , Humanos , Lactato Desidrogenases/sangue , Biópsia Líquida , Masculino , Melanoma/diagnóstico , Melanoma/terapia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
7.
Am J Med Genet A ; 179(3): 417-422, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30637922

RESUMO

Tetrasomy 18p is a rare chromosomal abnormality, resulting from an additional iso-chromosome composed of two copies of the short arm. It is characterized by craniofacial abnormalities, neuromuscular dysfunction, and developmental delay. The Chromosome 18 Clinical Research Center has established the largest cohort of individuals with this rare genetic condition. Here, we describe a case series of 21 individuals with tetrasomy 18p who have a previously unreported clinical finding: low bone mineral density. Most individuals met criteria for low bone density despite being relatively young (mean age of 21 years). Clinicians providing care to individuals affected by Tetrasomy 18p should be aware of their increased risk for decreased bone density and pathological fractures.

8.
Eur J Cancer ; 106: 12-23, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30453170

RESUMO

AIM: To characterise clinical presentation, laboratory and histopathologic characteristics and assess the treatment and outcome of neuromuscular side-effects of checkpoint therapy. METHODS: The side-effect registry and the institutional database from ten skin cancer centres were queried for reports on myositis and neuromuscular side-effects induced by checkpoint inhibitors. In total, 38 patients treated with ipilimumab, tremelimumab, nivolumab and pembrolizumab for metastatic skin cancer were evaluated and characterised. RESULTS: Myositis was the most frequent neuromuscular adverse event. In 32% of cases, myositis was complicated by concomitant myocarditis. Furthermore, cases of isolated myocarditis, myasthenia gravis, polymyalgia rheumatica, radiculoneuropathy and asymptomatic creatine kinase elevation were reported. The onset of side-effects ranged from the first week of treatment to 115 weeks after the start of therapy. Most of the cases were severe (49% grade III-IV Common Terminology Criteria for Adverse Events), and there were two fatalities (5%) due to myositis and myositis with concomitant myocarditis. Only half of the cases (50%) completely resolved, whereas the rest was either ongoing or had sequelae. Steroids were given in 80% of the resolved cases and in 40% of the unresolved cases. CONCLUSION: Immune-mediated neuromuscular side-effects of checkpoint inhibitors greatly vary in presentation and differ from their idiopathic counterparts. These side-effects can be life threatening and may result in permanent sequelae. Occurrence of these side-effects must be taken into consideration for patient information, especially when considering adjuvant immunotherapy with anti-programmed cell-death protein 1 (PD-1) antibodies and monitoring, which should include regular surveillance of creatine kinase.

9.
J Matern Fetal Neonatal Med ; 32(8): 1378-1387, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29132234

RESUMO

Preterm birth is a major health concern that affects 10% of all worldwide deliveries. Many preterm infants are discharged from the hospital with morbidities that lead to an increased risk for neurodevelopmental impairment, recurrent hospitalizations, and life-long conditions. Unfortunately, the treatment of these conditions is palliative rather than curative, which calls for novel and innovative strategies. Progress in regenerative medicine has offered therapeutic options for many of these conditions. Specifically, human umbilical cord mesenchymal stem cells (MSCs) and cord blood (UCB) cells have shown promise in treating adult-onset diseases. Unlike bone-marrow and embryonic derived stem cells, umbilical cord-derived cells are easily and humanely obtained, have low immunogenicity, and offer the potential of autologous therapy. While there are several studies to uphold the efficacy of umbilical cord MSCs in adult therapies, there remains an unmet need for the investigation of its use in treating neonates. The purpose of this review is to provide a summary of current information on the potential therapeutic benefits and clinical applicability of umbilical cord MSCs and UCB cells. Promising preclinical studies have now led to a research movement that is focusing on cell-based therapies for preterm infants.


Assuntos
Medicina Regenerativa/métodos , Cordão Umbilical/citologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Neonatologia/métodos , Geleia de Wharton/citologia
10.
Int J Cancer ; 144(5): 1147-1150, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30151962

RESUMO

Recent studies suggest that the age-related remodeling of the immune system, known as immunosenescence, could impact the efficacy of immune checkpoint inhibitors in leukemia or nonsmall cell lung cancer. We investigated whether senescence markers can predict response to checkpoint inhibitor therapy in melanoma patients. The peripheral blood of patients with newly diagnosed, untreated metastatic melanoma was analyzed by flow cytometry to correlate the frequency of senescence markers with clinical response as measured by RECIST after 12 weeks of treatment with immune checkpoint inhibitors. The loss of surface markers CD27 and CD28 or the expression of Tim-3 and CD57 on T cells was associated with resistance to checkpoint inhibitor blockade, presenting these phenotypes as possible predictive biomarkers for checkpoint inhibitor therapy. Immunosenescence seems to impact on the response to checkpoint inhibitor therapy in melanoma patients. Thus, lymphocyte phenotyping for senescence markers, with the introduction of immunosenescence panels, could be predictive for checkpoint inhibitor response.


Assuntos
Imunossenescência/imunologia , Melanoma/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Antígenos CD28/imunologia , Antígenos CD57/imunologia , Feminino , Citometria de Fluxo/métodos , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
11.
J Investig Med High Impact Case Rep ; 6: 2324709618800349, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30246038

RESUMO

Hemorrhagic shock is a rare, emergent condition that is often fatal in newborns. In this article, we report cases of 3 neonates presenting with acute, life-threatening hemorrhage who were subsequently diagnosed with severe hemophilia (<1% factor VIII). The first infant was tachycardic, pale, and had a precipitous drop in his hemoglobin secondary to a subgaleal hemorrhage. The second patient sustained a splenic rupture, a sequela that has been reported in only 4 other neonatal cases. The last infant presented with tonic-clonic seizures and respiratory distress. Head imaging demonstrated extracranial and intracranial hemorrhage, complications that can result in 20% mortality. All 3 patients were successfully treated with clotting factor concentrate and blood products. After normalization of factor VIII levels, the newborns did not develop any new hemorrhages and were discharged home within 3 weeks of birth. Pediatric providers should be aware that these signs and symptoms may be potentially lethal complications in neonates with severe factor VIII deficiency.

12.
Oncotarget ; 9(48): 28903-28909, 2018 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-29988983

RESUMO

Dual immune-checkpoint blockade with the anti-PD-1 antibody nivolumab (1 mg/kg) and standard-dose ipilimumab (3 mg/kg) is the mainstay of immunotherapy in advanced melanoma and it is approved since 2016. However, severe side effects (grade 3/4) occur in up to 60% of the patients. Recently, clinical trials have shown similar anti-tumor activity with a more favorable toxicity profile in patients treated with low-dose ipilimumab (1 mg/kg) and standard-dose pembrolizumab (2 mg/kg). In this study we report on the real-world experience of this dosing regime in advanced melanoma patients not eligible for clinical trials. A total of 33 patients with metastatic melanoma (24 with cutaneous and 9 with uveal melanoma) were assessed, retrospectively. Brain metastases were present in 33% of the patients and lactate dehydrogenase was elevated in 70%. Overall response rates were 38% and 0% in cutaneous melanoma and uveal melanoma respectively. Median overall survival was not reached in cutaneous melanoma and was 18 months in uveal melanoma. In 18% of the patients at least one treatment-related severe adverse event was observed. Our observation that the combination of standard dose pembrolizumab and low-dose ipilimumab has a favorable toxicity profile yet anti-tumor activity comparable to the approved standard-dose combination regime in advanced patients not suitable for enrollment in clinical trials is encouraging.

13.
Cells Tissues Organs ; 205(3): 137-150, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29949803

RESUMO

Mesenchymal stem cells (MSCs) have shown promise as therapeutic agents in treating morbidities associated with premature birth. MSCs derived from the human umbilical cord are easy to isolate and have low immunogenicity and a robust ability to secrete paracrine factors. To date, there are no studies evaluating preterm versus term umbilical cord tissue-derived MSCs. Therefore, our aim was twofold: (1) to compare stem cell properties in preterm versus term MSCs and (2) to examine the impact of oxygen tension on stem cell behavior. Umbilical cord tissue was obtained from 5 preterm and 5 term neonates. The cells were isolated and characterized as MSCs in accordance with the International Society for Cellular Therapy. We exposed MSCs to different oxygen tensions to examine the impact of environmental factors on cell performance. We studied the following stem cell properties: (i) motility, (ii) proliferation, (iii) senescence, (iv) cell viability, (v) colony-forming unit efficiency, and (vi) inflammatory cytokine expression. Under normoxia (21% O2), cells from preterm and term infants had similar properties. Under hypoxic conditions (1% O2), term MSCs had better cell proliferation; however, cells exposed to hyperoxia (90% O2) had the slowest motility and lowest cell viability (p < 0.05). There was no difference in the expression of senescence or cytokine expression between the groups. The term cells demonstrated more colony-forming efficiency than the preterm cells. In sum, our preliminary findings suggest that MSCs derived from term and preterm umbilical cords have similar characteristics, offering the potential of future autologous/allogeneic MSC transplants in neonates.


Assuntos
Células-Tronco Mesenquimais/citologia , Oxigênio/farmacologia , Nascimento Prematuro/patologia , Nascimento a Termo/fisiologia , Geleia de Wharton/citologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Citocinas/metabolismo , Humanos , Recém-Nascido , Mediadores da Inflamação/metabolismo
14.
Cell Transplant ; 27(3): 501-514, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29756518

RESUMO

Intranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, human mesenchymal stem cells (MSCs) were isolated from Wharton's jelly of umbilical cords and were labeled with extremely bright quantum dots (QDs) in order to track the cells efficiently. At 2 h after intranasal delivery in immunodeficient mice, the labeled cells were found under the olfactory epithelium, crossing the cribriform plate adjacent to the fila olfactoria, and associated with the meninges of the olfactory bulb. At all times, the cells were separate from actual nerve tracts; this location is consistent with them being in the subarachnoid space (SAS) and its extensions through the cribriform plate into the nasal mucosa. In their location under the olfactory epithelium, they appear to be within an expansion of a potential space adjacent to the turbinate bone periosteum. Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.


Assuntos
Sistema Nervoso Central/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Células Cultivadas , Humanos , Imuno-Histoquímica , Microscopia de Fluorescência , Nanopartículas/química , Nanotecnologia/métodos , Pontos Quânticos , Geleia de Wharton/citologia
15.
PLoS One ; 12(12): e0189895, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29261798

RESUMO

INTRODUCTION: Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating neurologic condition with high mortality rates and long-term complications for surviving infants. Mesenchymal stem/stromal cells (MSCs) have emerged as novel therapeutic agents with promising results in experimental studies of HIE. The purpose of this study is to (a) methodically review the current preclinical literature describing MSC therapy in animal models of HIE, (b) quantify the effect size in regards to functional neurologic outcome, and (c) identify research gaps/limitations that should be addressed prior to future preclinical and clinical studies. METHODS: Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed. Eligible studies were identified and data regarding study characteristics and outcome measures was extracted. After quality assessment, meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD). Funnel plots and Egger's tests were utilized to evaluate for the presence of publication bias. RESULTS: A total of 19 studies met inclusion in the current systematic review. Meta-analysis revealed that MSCs have a significant positive effect on neurobehavioral outcome following HIE injury. Sensorimotor function was improved by 2.25 SMD (95% CI; 2.04-2.46) in cylinder rearing and 2.97 SMD (95% CI; 2.56-3.38) in rotarod. Likewise, cognitive function was improved by 2.76 SMD (95% CI; 2.53-2.98) on the water maze and 2.97 SMD (95% CI; 2.58-3.35) in object recognition. Stratification demonstrated an increased effect size depending on various study characteristics. CONCLUSIONS: Overall, these results suggest a promising role for MSCs in preclinical studies of HIE. MSC treatment demonstrates improved functional outcomes that are encouraging for future translational studies. While risk of bias and heterogeneity limited the strength of our meta-analysis, our results are consistent with those seen in this field of research.


Assuntos
Hipóxia-Isquemia Encefálica/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Cognição , Humanos , Hipóxia-Isquemia Encefálica/fisiopatologia , Viés de Publicação , Resultado do Tratamento
16.
Am J Trop Med Hyg ; 97(5): 1405-1409, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29140242

RESUMO

Zika virus (ZIKV) emerged in Brazil in 2015, which was followed by an increase of Guillain-Barre Syndrome (GBS) cases. We report the epidemiological, clinical, and laboratory findings of the first six neurological cases associated with ZIKV in Brazil seen in a reference neurology hospital in Pernambuco, Brazil. In all cases, ZIKV was detected in serum and/or cerebrospinal fluid (CSF) samples. In this case series, four cases were defined as GBS, one as acute disseminated encephalomyelitis (ADEM) and the other as encephalitis. ZIKV was detected in all cases by RT-PCR and virus isolation was successful in two patients. The time between ZIKV acute symptoms and the development of neurological manifestations varied from 3 to 13 days and ZIKV was detected between 15 and 34 days after the initial symptoms. Our results highlight the need to include ZIKV as a differential diagnosis for neurological syndromes in countries with circulation of this arbovirus. Because the viremia in these patients appears to persist longer, direct diagnostic techniques such as RT-PCR and viral isolation should be considered even if it is after the acute phase of viral infection.


Assuntos
Encefalite/epidemiologia , Encefalomielite Aguda Disseminada/epidemiologia , Síndrome de Guillain-Barré/epidemiologia , Infecção por Zika virus/epidemiologia , Adulto , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Pré-Escolar , Encefalite/virologia , Encefalomielite Aguda Disseminada/virologia , Feminino , Síndrome de Guillain-Barré/virologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , RNA Viral/isolamento & purificação , Zika virus/isolamento & purificação
17.
J Mol Endocrinol ; 59(3): R109-R120, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28739632

RESUMO

Mesenchymal stem cells (MSCs) are self-renewing multipotent cells that have the capacity to secrete multiple biologic factors that can restore and repair injured tissues. Preclinical and clinical evidence have substantiated the therapeutic benefit of MSCs in various medical conditions. Currently, MSCs are the most commonly used cell-based therapy in clinical trials because of their regenerative effects, ease of isolation and low immunogenicity. Experimental and clinical studies have provided promising results using MSCs to treat diabetes. This review will summarize the role of MSCs on tissue repair, provide emerging strategies to improve MSC function and describe how these processes translate to clinical treatments for diabetes.


Assuntos
Diabetes Mellitus/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular , Separação Celular/métodos , Sobrevivência Celular , Terapia Baseada em Transplante de Células e Tecidos/métodos , Sangue Fetal/citologia , Terapia Genética/métodos , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Fenótipo , Regeneração , Transplante Homólogo
18.
J Pediatr Gastroenterol Nutr ; 64(5): 783-788, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28437326

RESUMO

OBJECTIVES: The aim of the study was to determine the acute and long-term outcomes of preterm infants treated with an intravenous fish oil-based lipid emulsion (FishLE) for parenteral nutrition-associated liver disease (PNALD). METHODS: Preterm infants 14 days to 24 months of age with anatomic short gut or severe intestinal dysmotility, serum direct bilirubin ≥4 mg/dL, and requiring >60% calories from parenteral nutrition were eligible. Enrolled infants received 1 g ·â€Škg ·â€Šday of FishLE until resolution of direct hyperbilirubinemia or return of enteral nutrition. Acute clinical effects and biochemical markers of liver function were monitored. Growth and developmental scores at 6 and 12 months postmenstrual age (PMA) were assessed and compared with controls matched by gestational age (GA). RESULTS: Thirteen patients with mean GA of 28 ±â€Š4 weeks were treated and compared with 119 GA-matched controls. Their mean direct bilirubin was 9.8 ±â€Š6.4 mg/dL at enrollment. All infants had resolution of cholestasis after study completion. There were no acute adverse events, deaths, or liver/intestinal transplants. Weight and head circumference were similar between FishLE-treated patients and controls at 6- and 12-month PMA. Cognitive and motor scores were decreased at 6 and 12 months PMA in FishLE-treated infants. Logistic regression analysis showed that prolonged hospitalization was detrimental to cognitive and motor development, whereas treatment was not. CONCLUSIONS: The use of intravenous FishLEs in premature infants appears to be safe and reverses PNALD despite significant liver disease and intestinal failure. This therapy should be used in preterm infants with PNALD and followed long term to evaluate development.


Assuntos
Emulsões Gordurosas Intravenosas/uso terapêutico , Óleos de Peixe/uso terapêutico , Doenças do Prematuro/terapia , Hepatopatias/terapia , Nutrição Parenteral/efeitos adversos , Feminino , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etiologia , Hepatopatias/etiologia , Modelos Logísticos , Masculino , Estudos Prospectivos , Resultado do Tratamento
19.
An Bras Dermatol ; 92(1): 72-80, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28225960

RESUMO

Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.


Assuntos
Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Inflamação/complicações , Inflamação/diagnóstico , Dermatopatias/etiologia , Humanos , Inflamação/imunologia , Dermatopatias/imunologia
20.
An. bras. dermatol ; 92(1): 72-80, Jan.-Feb. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-838007

RESUMO

ABSTRACT Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.

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