Addition of an alginate to a modified zeolite improves hemostatic performance in a swine model of lethal groin injury.

BACKGROUND: QuikClot is a zeolite-based hemostatic agent that can control severe hemorrhage through adsorption of water in an exothermic reaction. Ion exchanging the calcium ions in zeolite type 5A with cations of a reduced hydration enthalpy can reduce heat generation, but its effect on the hemostatic efficacy is not clear. We developed a new compound zeolite hemostat and tested it against controls in a modified swine model of battlefield injury. METHODS: A modified complex groin injury was created in 42 swine (39.4 +/- 2.6 kg). This included semitransection of the proximal thigh (level of inguinal ligament) and semidivision of the femoral artery and vein. After 3 minutes, the animals were assigned to (1) no dressing (ND), (2) standard dressing (SD), (3) SD + zeolite hemostat (QC), (4) SD + chemically modified zeolite hemostat, where calcium was substituted with silver (Ag) and zinc (Zn) simultaneously, (Ag.Zn-zeolite), and (5) SD+ the compound hemostat composed of Ag.Zn-zeolite and alginate. Resuscitation was started 15 minutes after application of dressing (500 mL of 6% hetastarch during 30 minutes). Survival for 180 minutes was the primary endpoint for this study. Blood loss, wound temperatures, and histologic tissue damage were recorded as well. In addition, the antibacterial activities of these hemostatic agents were tested on agar plates. At the end of experiment, the strength of clots was carefully measured by a Tablet Hardness Analyzer. RESULTS: Mortality in the group treated with the application of the compound hemostat composed of Ag.Zn-zeolite and alginate was 10% versus 100% in the ND group and 71% in the SD group (p < 0.001 vs. ND group, p < 0.05 vs. SD group). The QC group had a mortality rate of 22%, whereas application of Ag- and Zn-substituted zeolite associated with a mortality rate of 37.5%. Ag and Zn substitution of zeolite reduced the in vivo temperature peak to 39.8 degrees C +/- 2.3 degrees C and no thermal injury of tissue was noted in these groups. Ag- and Zn-substituted zeolite posed an antibacterial ability against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Addition of an alginate into the modified zeolite hemostat reinforced the strength of clots to 18.52 N +/- 1.33 N. CONCLUSIONS: Application of the compound zeolite hemostat can effectively control hemorrhage and dramatically reduce mortality from a lethal groin wound. In addition to its antibacterial properties, Ag- and Zn-substituted zeolite hemostat can decrease the exothermic reaction and greatly attenuate the heat-induced tissue injury.

Differentiation of the pericyte in wound healing: The precursor, the process, and the role of the vascular endothelial cell.

Pericytes play a crucial role in the homeostasis and maturation of newly formed vessels, but their precursor and the process of their differentiation remain unclear. In this study, we show that in vivo, pericytes in human granulation tissue taken from burn patients expressed CD13 and collagen I, which are cell markers of peripheral blood fibrocytes (PBFCs). Mouse PBFCs, ex vivo labeled by PKH-26 and administered intravenously back to mice, formed lumens in the granulation tissue and expressed pericyte marker NG2. Furthermore, in cell culture, human PBFCs in co-culture with human umbilical vascular endothelial cells or human dermal microvascular endothelial cells (HDMECs) expressed pericyte markers desmin and myosin heavy chain of smooth muscle cell, and some migrated to the membrane of human umbilical vascular endothelial cells or HDMECs to form PBFC/vascular endothelial cell clusters, or formed round PBFC only clusters with their nuclei aligned along a circle. The formation of PBFC/vascular endothelial cell clusters and round PBFC clusters were inhibited by an antibody against monocyte chemotactic protein-1. PBFCs cultured with homogenate of granulation tissue also expressed desmin and myosin heavy chain of smooth muscle cell. Our findings support that the PBFC is a precursor of pericytes, the differentiation of PBFCs is induced by vascular endothelial cells in a paracrine fashion.

Serum levels of surface large envelope proteins: prognostic markers for hepatitis B e antigen-negative patients with adefovir dipivoxil treatment.

BACKGROUND: The present investigation was undertaken to evaluate the prognostic role of pretreatment serum hepatitis B virus (HBV) surface large envelope protein (LHBs) levels in the curative effects after 48-week adefovir dipivoxil (ADV) treatment. METHODS: A total of 128 patients received ADV once daily for 48 weeks. Serum levels of LHBs were detected by ELISA. Real-time quantitative PCR was used to analyse HBV genotype and HBV DNA copies in serum. Receiver operating characteristic (ROC) curve analysis was performed to assess the optimal cutoff value of pretreatment LHBs for predicting the curative effects of ADV treatment. RESULTS: After ADV treatment for 48 weeks, viral response and partial response were 31.4% (16/51) and 29.4% (15/51), respectively, in patients from the hepatitis B e antigen (HBeAg)-positive group; viral response and partial response were 39.7% (27/68) and 39.7% (27/68), respectively, in patients from the HBeAg-negative group. HBeAg-negative patients with high serum levels of LHBs had low response rates to antiviral therapy. ROC curve analysis showed that HBeAg-negative patients with serum LHBs levels > or =3.889 microg/ml at baseline predicted non-response to antiviral therapy. The sensitivity was 42.5% and specificity was 92.86%. Among a total of 19 patients with high serum levels of LHBs (> or =3.889 microg/ml) at baseline, only 2 (11%) patients responded to antiviral therapy. There was no correlation observed between HBV genotype and effects of ADV treatment. CONCLUSIONS: HBeAg-negative patients with high serum levels of LHBs (> or =3.889 microg/ml) at baseline should not be recommended to receive ADV treatment.