George M. Wairiuko

High passage number of stem cells adversely affects stem cell activation and myocardial protection.

ABSTRACT Progenitor cell plasticity enhances positive remodeling of damaged tissue. We and others have previously shown that progenitor cells may limit apoptosis and modulate inflammation in part by the production of growth factors. However, recent studies suggest that progenitor cells senesce and lose their differentiation potential with increasing time in culture and passage. We hypothesize that murine bone marrow mesenchymal stem cells (MSCs) are cardioprotective against ischemia/reperfusion injury in the isolated perfused rat heart, and that passage number has an adverse effect on MSC activation and cardioprotection. Adult male and female Sprague-Dawley rat hearts were isolated, perfused via Langendorff model, and subjected to ischemia/reperfusion. Mouse MSCs were harvested, cultured, suspended in perfusate, and infused before global index ischemia. Hearts were assigned to controls or infusion with passage 3, 5, or 10 MSCs. In addition, MSCs in culture were stressed by hypoxia and increasing doses of endotoxin (lipopolysaccharide). Mesenchymal stem cell activation was determined by measuring vascular endothelial growth factor production with enzyme-linked immunosorbent assay. All data are reported as mean ± SEM and were analyzed with 2-way analysis of variance. Differences are considered significant if P < 0.05. Passage 3 murine MSC infusion in hearts before ischemia reduced the depression of left ventricular developed pressure, attenuated the increase of end-diastolic pressure, and reduced the depression of +dP/dT and −dP/dT. However, the MSC protective effect disappeared in hearts infused with passage 5 and passage 10 MSCs. Although hypoxia and lipopolysaccharide resulted in significant activation of MSCs, passage 3 MSCs demonstrated significantly greater vascular endothelial growth factor release than passage 5 and 10 MSCs. Acute murine MSC infusion confers protection in isolated rat hearts. However, high passage number has an adverse effect on MSC activation and protection. This portends limited ex vivo expansion before possible therapeutic use.

Cytokines in necrotizing enterocolitis.

ABSTRACT Necrotizing enterocolitis (NEC) is a devastating intra-abdominal emergency in the newborn period. The disease involves bowel wall inflammation, ischemic necrosis, eventual perforation, and the need for urgent surgical intervention. Unrecognized or left untreated, the neonate can decompensate quickly, often progressing to shock, multisystem organ failure, and eventual death. During the past several years, a number of basic science and clinical trials have been established in an attempt to understand the pathophysiology of NEC. As many researchers feel that NEC develops as an uncontrolled inflammatory response that leads to intestinal ischemia, a large number of studies have been focused on the inflammatory cascade and the role that cytokines play within that cascade. Although a large amount of data has been generated from these studies, the events leading to the ischemic injury of the intestine are still not fully understood. This article will therefore focus on the key cytokines involved with NEC, in an attempt to present the current literature and studies that support their involvement.

Influence of bactibilia after preoperative biliary stenting on postoperative infectious complications

The aim of this study was to correlate the bactibilia found after preoperative biliary stenting with that of the bacteriology of postoperative infectious complications in patients with obstructive jaundice. One hundred thirty-eight patients (83% malignant and 17% benign etiologies) with obstructive jaundice had both their bile and all postoperative infectious complications cultured. Eighty-six (62%) had preoperative biliary stents (stent group) and 52 (38%) did not (no-stent group). There were no differences for age, sex, incidence of malignancy, type of operation, estimated blood loss, transfusion requirements, hospital length of stay, morbidity, or mortality rates between the two groups. Of 31 infectious complications, 23 were in the stent group and eight were in the no-stent group (P > 0.05), but only 13 (42%) infectious complications had bacteria that were also cultured from the bile. Only wound infection (P = 0.03) and bacteremia (P = 0.04) were more likely to occur in stented patients. Taken together, these data show that preoperative biliary stenting increases the incidence of bactibilia, bacteremia, and wound infection rates but does not increase morbidity, mortality, or hospital length of stay. Jaundiced patients can undergo preoperative biliary stenting while maintaining an acceptable postoperative morbidity rate.