Co-transplantation of Xenogeneic Bone Marrow–derived Mesenchymal Stem Cells Alleviates Rejection of Pancreatic Islets in Non-obese Diabetic Mice

Bone marrow–mesenchymal stem cells (BM-MSCs) have generated a great perspective in the field of regenerative medicine, and also in the treatment of inflammatory and autoimmune diseases in the past decade due to their immunomodulatory and anti-inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs and pancreatic islets co-transplantation obtained from Wistar rats in preventing rejection or inducing tolerance to islet transplantation in non-obese diabetic mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group). Compared to the islet group, islet + MSCs had a lower expression of inflammatory markers, such as, tumor necrosis factor– α (13.40 ± 0.57 vs. 9.90 ± 0.12, P = .01), monocyte chemoattractant protein 1 (51.30 ± 6.80 vs. 9.00 ± 1.80, P = .01), and interleukin 1β (IL-1β) (16.2 ± 1.65 vs. 6.80 ± 1.00, P = .04). Comparing the expression of immune tolerance markers, it is noted that animals receiving the co-transplantation showed a significantly higher expression than the islet group of IL-4 (25.60 ± 1.96 vs. 2.80 ± 0.20, P = .004), IL-10 (188.40 ± 4.60 vs. 4.55 ± 0.12, P = .0001), and forkhead box P3 (34.20 ± 1.3 vs. 1.30 ± 0.2, P = .004), respectively. These results suggest an immunomodulatory action of BM-MSC in islet xenotransplantation showing that these stem cells have the potential to mitigate the early losses of grafts, due to the regulation of the inflammatory process of transplantation.     

Abdominal Complications After Lung Transplantation in a Brazilian Single Center

Surgical and nonsurgical abdominal complications have been described after lung transplantation. However, there is limited data on this event in this population. The objective of this study was to analyze the incidence of abdominal complications in patients undergoing lung transplantation at the Heart Institute of the Faculty of Medicine, University of São Paulo (InCor-HCFMUSP) between the years 2003 and 2016. The main causes of abdominal complications were inflammatory acute abdomen (7 patients; 14%), obstructive acute abdomen (9 patients; 18%), gastroparesis (4 patients; 8%), distal intestinal obstruction syndrome (4 patients; 8%), perforated acute abdomen (7 patients; 14%), cytomegalovirus (CMV; 6 patients; 12%), and other reasons (12 patients; 26%). Separating these patients according to Clavien-Dindo classification, we had 21 patients (43%) with complications grade II, 4 patients (8%) with complications grade IIIa, 7 patients (14%) with grade IIIb complications, 7 patients (14%) with grade IV complications, and 10 patients (21%) with grade complications V. In conclusion, abdominal disorders are seriously increased after lung transplantation and correlate with a high mortality. Early abdominal surgical complication has worse prognosis.     

Association Between Readmission After Liver Transplant and Adverse Immunosuppressant Reactions: A Prospective Cohort With a 1-Year Follow-up

Objective

To measure the association between readmission after liver transplantation and corresponding adverse drug reactions.

Transcutaneous Electrical Stimulation of PC5 and PC6 Acupoints Modulates Autonomic Balance in Heart Transplant Patients: A Pilot Study

The increased resting heart rate (HR) in heart transplant patients is associated with enhanced metabolic demand, the potential for fatigue, and lower quality of life. In the present study, we hypothesized that transcutaneous electrical acupoint stimulation (TEAS) could modulate autonomic balance and reduce resting HR in these patients. A single-arm clinical trial was conducted with patients aged > 18 years, at ambulatorial accompaniment after heart transplantation, who were submitted to a single TEAS (40 minutes at pericardium channel acupoints PC5 and PC6). The arterial blood pressure and RR interval were recorded from 20 minutes before to 20 minutes after TEAS. The RR intervals were used to calculate HR variability (HRV) and the sympathovagal index. Linear mixed models were used for comparing variables before, during, and after TEAS. The significance level was set as P < 0.05. TEAS acutely improved HRV in transplant patients and enhanced the sympathovagal index during its application. Significant increases in systolic and diastolic blood pressure and mean arterial pressure were observed at recovery, such as a slight, but significant, decrease in HR. In conclusion, TEAS at PC5 and PC6 acutely modulates HRV and hemodynamics in transplant patients.     

Association Safety of Liver Preservation Solutions at the State University of Campinas From 2010 to 2014

The probable reason for mixing solutions during the harvesting procedure is due to the presence of multiple transplant teams that have their own solution usage tradition. Despite numerous studies comparing the efficacy of different preservation solutions, there is no study addressing the associating solution and if there is any impact on liver graft and patient survival. The aim was to evaluate the effect of the association of preservation solutions during the harvesting procedure on liver transplantation outcomes, especially in relation to the degree of preservation injury in the postreperfusion period and patient survival. We analyzed 206 transplants that were distributed as follows: when there was association (89/206 = 43.2%) and when there was no association (117/206 = 56.8%). There was a statistically significant difference in relation to the degree of preservation injury correlated to cold ischemia time (P = .009, odds ratio 1.992; 95% confidence interval 1.185–3.347). Severe harvesting (grades III and IV) was 71.8% when the solution was not associated (P = .008). There was no difference regarding patient survival either. We found that the association of liver preservation solutions has no impact on patient survival, so it can be done safely. The best survival rate was associated with minimal harvesting.     

Age related macular degeneration and drusen: neuroinflammation in the retina

Inflammation protects from dangerous stimuli, restoring normal tissue homeostasis. Inflammatory response in the nervous system ("neuroinflammation") has distinct features, which are shared in several diseases. The retina is an immune-privileged site, and the tight balance of immune reaction can be disrupted and lead to age-related macular disease (AMD) and to its peculiar sign, the druse. Excessive activation of inflammatory and immunological cascade with subsequent induction of damage, persistent activation of resident immune cells, accumulation of byproducts that exceeds the normal capacity of clearance giving origin to a chronic local inflammation, alterations in the activation of the complement system, infiltration of macrophages, T-lymphocytes and mast-cells from the bloodstream, participate in the mechanisms which originate the drusen. In addition, aging of the retina and AMD involve also para-inflammation, by which immune cells react to persistent stressful stimuli generating low-grade inflammation, aimed at restoring function and maintaining tissue homeostasis by varying the set point in relation to the new altered conditions. This mechanism is also seen in the normal aging retina, but, in the presence of noxious stimuli as in AMD, it can become chronic and have an adverse outcome. Finally, autophagy may provide new insights to understand AMD pathology, due to its contribution in the removal of defective proteins. Therefore, the AMD retina can represent a valuable model to study neuroinflammation, its mechanisms and therapy in a restricted and controllable environment. Targeting these pathways could represent a new way to treat and prevent both exudative and dry forms of AMD.