Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment

Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI. In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products improved cardiac function and limited adverse cardiac remodeling 12 weeks post-ischemic injury, supporting sustained and long-term beneficial therapeutic effect. Donor associated variability was found in the modulation of cardiac remodeling and activation of the Akt-mTOR-GSK3ß survival pathway. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from UCM-MSCs proliferation and expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.This work was funded by European Structural and Investment Funds (ESIF), under Lisbon Portugal Regional Operational Programme and National Funds through Fundação para a Ciência e Tecnologia (FCT) ([POCI-01-0145-FEDER-030985], [POCI-01-0145-FEDER-016385]); by FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of individual funding [CEECINST/00091/2018] to DN and by QREN funds through the project ClinUCX (QREN 30196) and individual fellowships: [PD/BD/127997/2016] to TL, [SFRH/BD/144490/2019] to RG and [SFRH/BD/111799/2015] to VS-P. The funding bodies other than ECBio had no role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication

Electromagnetic fields at the sea bottom induced by a line of immersed electric dipoles

The analysis of electromagnetic fields caused by alternate or transient electric currents flowing along a cable in sea water has several applications. It supports the interpretation of electromagnetic geophysical data and safety procedures against the threat of sea mines. The approach to the problem employs a magnetic vector potential in the frequency domain due to a pulse source electric dipole, and performs Laplace and Hankel transforms and integration along the cable, to describe the variation of the magnetic induction field due to an electric dipole of finite length. The result is applicable to shallow or deep sea water environments, adaptable to any transmitting current waveform and useful for wave-field separation. The prospects relate to a horizontal receiving coil at the sea bottom and simulate: a minesweeper campaign with a current source at the sea surface or a geophysical survey with a current source close to the sea floor. Therefore, the present analysis may serve: to define parameters in counter-sweeping of submarine mines; to map the conductivity of sediments under shallow waters for the prevention and control of contamination; and as a first approach in the characterization of offshore mineral and oil economic deposits.A análise de campos eletromagnéticos causados por correntes alternadas ou transientes fluindo ao longo de um cabo na água do mar tem várias aplicações. Ela prove suporte à interpretação de dados geofísicos eletromagnéticos e aos procedimentos de segurança contra a ameaça de minas submarinas. A abordagem do problema emprega um potencial vetorial magnético, no domínio da frequência, devido a um dipolo elétrico com uma fonte tipo pulso e calcula transformações de Laplace e de Hankel e integração ao longo do comprimento do cabo, para descrever a variação temporal do campo magnético de indução devido a um dipolo elétrico de comprimento finito. O resultado é aplicável em ambientes de água do mar rasa ou profunda, adaptável para qualquer forma de onda de corrente transmitida e útil para separação de campos de ondas. As configurações se referem a uma bobina receptora horizontal no fundo do mar e simulam: uma campanha de varredura de minas submarinas com uma fonte de corrente na superfície ou um levantamento geofísico com uma fonte de corrente próxima ao assoalho do mar. Portanto, a presente análise pode servir: para definir parâmetros em contra-varredura de minas submarinas; para mapear a condutividade de sedimentos sob águas rasas em prevenção e controle de contaminação e como uma primeira abordagem na caracterização de depósitos minerais e de hidrocarbonetos no mar

Vasodilator factors in the systemic and local adaptations to pregnancy

We postulate that an orchestrated network composed of various vasodilatory systems participates in the systemic and local hemodynamic adaptations in pregnancy. The temporal patterns of increase in the circulating and urinary levels of five vasodilator factors/systems, prostacyclin, nitric oxide, kallikrein, angiotensin-(1–7) and VEGF, in normal pregnant women and animals, as well as the changes observed in preeclamptic pregnancies support their functional role in maintaining normotension by opposing the vasoconstrictor systems. In addition, the expression of these vasodilators in the different trophoblastic subtypes in various species supports their role in the transformation of the uterine arteries. Moreover, their expression in the fetal endothelium and in the syncytiotrophoblast in humans, rats and guinea-pigs, favour their participation in maintaining the uteroplacental circulation. The findings that sustain the functional associations of the various vasodilators, and their participation by endocrine, paracrine and autocrine regulation of the systemic and local vasoactive changes of pregnancy are abundant and compelling. However, further elucidation of the role of the various players is hampered by methodological problems. Among these difficulties is the complexity of the interactions between the different factors, the likelihood that experimental alterations induced in one system may be compensated by the other players of the network, and the possibility that data obtained by manipulating single factors in vitro or in animal studies may be difficult to translate to the human. In addition, the impossibility of sampling the uteroplacental interface along normal pregnancy precludes obtaining longitudinal profiles of the various players. Nevertheless, the possibility of improving maternal blood pressure regulation, trophoblast invasion and uteroplacental flow by enhancing vasodilation (e.g. L-arginine, NO donors, VEGF transfection) deserves unravelling the intricate association of vasoactive factors and the systemic and local adaptations to pregnancy

Prevention of repeated episodes of type 2 reaction of leprosy with the use of thalidomide 100 mg/day

BACKGROUND: Leprosy can have its course interrupted by type 1 and 2 reactional episodes, the last named of erythema nodosum leprosum (ENL). Thalidomide has been the medication of choice for the control of ENL episodes since 1965. OBJECTIVES: These episodes can repeat and cause damages to the patient. In order to prevent these episodes, an extra dose of 100 mg/day thalidomide was used during six months, followed by a follow-up period of six more months after thalidomide discontinuation. METHODS: We included 42 patients with multibacillary (MB) leprosy who had episodes of ENL. They were male and female patients aged between 18 and 84 years. RESULTS: Of the 42 patients, 39 (92.85%) had the lepromatous form and three (7.15%) had the borderline form. We found that 100% of patients had no reactional episode during the use of the drug. During the follow-up period after thalidomide discontinuation, 33 (78.57%) patients had no reactional episode and nine (21.43%), all of them with the lepromatous form, had mild episodes, which were controlled using non-steroidal anti-inflammatory. There were no thalidomide-related side effects. CONCLUSION: A maintenance dose of 100 mg/day of thalidomide showed to be effective to prevent repeated type 2 reactional episodes of ENL.Univ Estadual Paulista Julio de Mesquita Filho Un, Botucatu, SP, BrazilUniv Estadual Paulista Julio de Mesquita Filho Un, Botucatu, SP, Brazi