The Effect of Isovolemic Hemodilution with Oxycyte®, a Perfluorocarbon Emulsion, on Cerebral Blood Flow in Rats

BACKGROUND: Cerebral blood flow (CBF) is auto-regulated to meet the brain's metabolic requirements. Oxycyte is a perfluorocarbon emulsion that acts as a highly effective oxygen carrier compared to blood. The aim of this study is to determine the effects of Oxycyte on regional CBF (rCBF), by evaluating the effects of stepwise isovolemic hemodilution with Oxycyte on CBF. METHODOLOGY: Male rats were intubated and ventilated with 100% O(2) under isoflurane anesthesia. The regional (striatum) CBF (rCBF) was measured with a laser doppler flowmeter (LDF). Stepwise isovolemic hemodilution was performed by withdrawing 4ml of blood and substituting the same volume of 5% albumin or 2 ml Oxycyte plus 2 ml albumin at 20-minute intervals until the hematocrit (Hct) values reached 5%. PRINCIPAL FINDINGS: In the albumin-treated group, rCBF progressively increased to approximately twice its baseline level (208+/-30%) when Hct levels were less than 10%. In the Oxycyte-treated group on the other hand, rCBF increased by significantly smaller increments, and this group's mean rCBF was only slightly higher than baseline (118+/-18%) when Hct levels were less than 10%. Similarly, in the albumin-treated group, rCBF started to increase when hemodilution with albumin caused the CaO(2) to decrease below 17.5 ml/dl. Thereafter, the increase in rCBF was accompanied by a nearly proportional decrease in the CaO(2) level. In the Oxycyte-treated group, the increase in rCBF was significantly smaller than in the albumin-treated group when the CaO(2) level dropped below 10 ml/dl (142+/-20% vs. 186+/-26%), and rCBF returned to almost baseline levels (106+/-15) when the CaO(2) level was below 7 ml/dl. CONCLUSIONS/SIGNIFICANCE: Hemodilution with Oxycyte was accompanied with higher CaO(2) and PO(2) than control group treated with albumin alone. This effect may be partially responsible for maintaining relatively constant CBF and not allowing the elevated blood flow that was observed with albumin

Inclusivity and diversity : integrating international perspectives on stem cell challenges and potential

Regenerative medicine has great potential. The pace of scientific advance is exciting and the medical opportunities for regeneration and repair may be transformative. However, concerns continue to grow, relating to problems caused both by unscrupulous private clinics offering unregulated therapies based on little or no evidence and by premature regulatory approval on the basis of insufficient scientific rationale and clinical evidence. An initiative by the InterAcademy Partnership convened experts worldwide to identify opportunities and challenges, with a focus on stem cells. This was designed to be inclusive and consensus outputs reflected the diversity of the global research population. Among issues addressed for supporting research and innovation while protecting patients were ethical assessment; pre-clinical and clinical research; regulatory authorization and medicines access; and engagement with patients, policy makers, and the public. The InterAcademy Partnership (IAP) identified options for action for sharing good practice and building collaboration within the scientific community and with other stakeholders worldwide.http://stemcellreports.cell.comdm2022Immunolog

Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis.

Stem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM.We pooled participant-level data from twenty-two eligible clinical trials that satisfied our inclusion criteria, with a total of 524 patients. There were significant differences in the outcome based on the type and source of the infused cells. Out of all T1DM patients who received CD34+ hematopoietic stem cell (HSC) infusion, 58.9% became insulin independent for a mean period of 16 months, whereas the results were uniformly negative in patients who received umbilical cord blood (UCB). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) provided significantly beneficial outcome in T1DM, when compared to bone-marrow mesenchymal stem cells (BM-MSCs) (P<0.0001 and P = 0.1557). Administration of stem cell therapy early after DM diagnosis was more effective than intervention at later stages (relative risk = 2.0, P = 0.0008). Adverse effects were observed in only 21.72% of both T1DM and T2DM stem cell recipients with no reported mortality. Out of all poor responders, 79.5% were diagnosed with diabetic ketoacidosis.Stem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34+ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy

Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs) therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed

Modern Approach To Financial Time Series Analysis

This thesis is devoted to the multivariate canonical ARMA model and then continues with determination of a graphical model. Graphical model includes also relations between contemporaneous variables, not only dependence on past variables. In the practical part of this work canonical AR model is identi ed using software Mathematica. In this model we specify structural autoregresion according to the graphical models methodology. A time series of exchange rates was processed. It is together with program included on the enclosed CD

Baseline characteristics of the study populations in the 22 studies included in this analysis.

<p>Baseline characteristics of the study populations in the 22 studies included in this analysis.</p

Flow diagram showing record identification, screening and study inclusion process.

<p>Flow diagram showing record identification, screening and study inclusion process.</p

Stem cell therapy for type 2 DM.

<p>(A-D) Bar graphs depicting the change in C-peptide and HbA1c levels from baseline and 12 months after administration of different types of stem cells. UCB and BM-MNCs were injected intra-pancreatically <i>(n</i> = 3 and <i>n</i> = 107, respectively), while UC-MSCs and PD-MSCs were injected intravenously <i>(n</i> = 22 and <i>n</i> = 10, respectively). (E-F) Line graphs showing changes in C-peptide and HbA1c levels over time at baseline, 3, 6 and 12 months after stem cell therapy in T2DM patients. All data are expressed as the mean ± SEM. **** P < 0.0001.</p

Stem cell therapy for type 1 DM.

<p>(A-C) Comparison of the outcome of different types of stem cells in T1DM by Intravenous administration of Umbilical Cord Blood (UCB, <i>n</i> = 61), Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs, <i>n</i> = 15) and Bone Marrow Hematopoietic Stem Cells (BM-HSCs, <i>n</i> = 82) (D-E) Bar graphs depicting the change in C-peptide and HbA1c levels from baseline and 12 months after intravenous administration of different types of stem cells. (F-G) Line graphs showing changes in C-peptide and HbA1c levels over time at baseline, 3, 6 and 12 months after stem cell therapy in T1DM patients. All data are expressed as the mean ± SEM. **** P < 0.0001.</p