These results suggest a link between high level of GAD-Ab and some cases of cerebellar ataxia, particularly women with IDDM. If high serum levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluated for the presence of oligoclonal IgG bands and intrathecal synthesis of GAD-Ab to further prove an autoimmune origin of the syndrome.
BackgroundThe optimal timing of cardiac stem cells administration is still unclear. We assessed the safety of same-day and delayed (one week) delivery and the possible influence of the timing on the therapeutic outcomes of allogeneic porcine cardiac stem cells administration after acute myocardial infarction in a closed-chest ischemia-reperfusion model.MethodsFemale swine surviving 90 min occlusion of the mid left anterior descending coronary artery received an intracoronary injection of 25x106 porcine cardiac stem cells either two hours (n = 5, D0) or 7 days (n = 6, D7) after reperfusion. Controls received intracoronary injection of vehicle on day 7 (n = 6, CON). Safety was defined in terms of absence of major cardiac events, changes to the ECG during injection, post-administration coronary flow assessed using the TIMI scale and cardiac troponin I determination after the intervention. Cardiac Magnetic Resonance was performed for morphological and functional assessment prior to infarction, before injection (D7 and CON groups only), at one and 10 weeks. Samples were taken from the infarct and transition areas for pathological examination.ResultsNo major adverse cardiac events were seen during injection in any group. Animals receiving the therapy on the same day of infarction (D0 group) showed mild transient ST changes during injection (n = 4) and, in one case, slightly compromised coronary flow (TIMI 2). Cardiac function parameters and infarct sizes were not significantly different between groups, with a trend towards higher ejection fraction in the treated groups. Ventricular volumes indexed to body surface area increased over time in control animals, and decreased by the end of the study in animals receiving the therapy, significantly so when comparing End Diastolic Volume between CON and D7 groups (CON: 121.70 ml/m2 ± 26.09 ml/m2, D7: 98.71 ml/m2 ± 8.30 ml/m2, p = 0.037). The treated groups showed less organization of the collagenous scar, and a significantly (p = 0.019) higher amount of larger, more mature vessels at the infarct border.ConclusionsThe intracoronary injection of 25x106 allogeneic cardiac stem cells is generally safe, both early and 7 days after experimental infarction, and alleviates myocardial dysfunction, with a greater limitation of left ventricular remodeling when performed at one week.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0512-2) contains supplementary material, which is available to authorized users.
IntroductionThe intrapericardial delivery has been defined as an efficient method for pharmacological agent delivery. Here we hypothesize that intrapericardial administration of cardiosphere-derived cells (CDCs) may have an immunomodulatory effect providing an optimal microenvironment for promoting cardiac repair. To our knowledge, this is the first report studying the effects of CDCs for myocardial repair using the intrapericardial delivery route.Material and MethodsCDCs lines were isolated, expanded and characterized by flow cytometry and PCR. Their differentiation ability was determined using specific culture media and differential staining. 300,000 CDCs/kg were injected into the pericardial space of a swine myocardial infarcted model. Magnetic resonance imaging, biochemical analysis of pericardial fluid and plasma, cytokine measurements and flow cytometry analysis were performed.ResultsOur results showed that, phenotype and differentiation behavior of porcine CDCs were equivalent to previously described CDCs. Moreover, the intrapericardial administration of CDCs fulfilled the safety aspects as non-adverse effects were reported. Finally, the phenotypes of resident lymphocytes and TH1 cytokines in the pericardial fluid were significantly altered after CDCs administration.ConclusionsThe pericardial fluid could be considered as a safe and optimal vehicle for CDCs administration. The observed changes in the studied immunological parameters could exert a modulation in the inflammatory environment of infarcted hearts, indirectly benefiting the endogenous cardiac repair.
Biofiltration has been established as a promising alternative to conventional air pollution control technologies. However, gas biofilters modeling has been less developed than experimental research due to the complexity of describing the fundamental processes and the lack of globally accepted\ud
physical, chemical and biological parameters. In addition, biofiltration modeling based on degradation activity of fungi has been rarely considered.\ud
For this reason, in thiswork, a dynamic model describing toluene abatement by a bacterial and fungal biofilter is developed, calibrated and validated.\ud
The mathematical model is based on detailed mass balances which include the main processes involved in the system: convection, absorption, diffusion and biodegradation. The model was calibrated and validated using experimental data obtained from two equal lab-scale biofilters packed\ud
with coconut fiber and pine leaves, respectively. Both reactors were operated under similar conditions during 100 days at an empty bed residence time of 60 s and an average inlet load of 77 g toluenem−3 h−1. Biofilters were initially inoculated with a bacterial consortium, even though reactors\ud
were mostly colonized by fungi after 60 days of operation according to microscopic observation and reactors pH. Removal efficiency increased notably from 20% for the bacterial period to 80% for the fully developed fungal biofilters. Since kinetic parameters are strongly dependent on the\ud
biological population, semi-saturation constants for toluene and maximum growth rates were determined for bacterial and fungal operation periods.\ud
Kinetic parameters were fitted by means of an optimization routine using either outlet concentrations or removal efficiency data from the coconut fiber biofilter. A novel procedure in gas biofilters modeling was considered for checking the model calibration, by the assessment of the parameters confidence interval based on the Fisher Information Matrix (FIM). Kinetic parameters estimated in the coconut fiber reactor were validated in the pine leaves biofilter for bacterial and fungal operation. Adequate model fitting to the experimental outlet gas concentration for both bacterial and fungal operation periods was verified by using a standard statistical test.Peer ReviewedPostprint (published version
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