LY 225910

Clinical and immunohistochemical performance of lyophilized platelet-rich fibrin (Ly-PRF) on tissue regeneration.[Pubmed:28192870]

Clin Implant Dent Relat Res. 2017 Jun;19(3):466-477.

BACKGROUND: Platelet-rich fibrin (PRF) has been widely used in oral implantology and other fields, but benefits of the fresh PRF (FPRF (fresh platelet-rich fibrin)) were consequently limited because of its short-term application. Thus, a protocol for the combination of PRF and lyophilization comes up in the present study to address the issue of PRF storage and delayed clinical application, which has little been reported in this field at home and abroad by now. PURPOSE: The aim of the present study was to evaluate the applicability of lyophilized platelet-rich fibrin (Ly-PRF) used as the scaffold material for craniofacial tissue regeneration and to compare its biochemical properties with commonly used fresh PRF. MATERIALS AND METHODS: Two volunteers with both genders were selected as the source of PRF and Ly-PRF samples. Macro- and micro-scopic appearance evaluation as well as immunohistochemical comparison were performed on PRF samples before and after freeze-drying at -196 degrees C. The second experimental phase was to observe clinical performance when fresh and lyophilized PRF were applied in guided bone regeneration (GBR) operations in 39 patients losing teeth in the anterior maxillary region who required an oral implantation followed by labial bone grafting. RESULTS: The conventional histological and transmission electron microscopy images showed the microstructure of Ly-PRF, which resembled a mesh containing apparently irregularly shaped platelets with less alpha-granule than fresh PRF in micro and a translucent membrane with less elasticity than fresh PRF in macro. Simultaneous immunohistological staining results showed positive expression of PDGF-BB, IL-1, IL-4, TNF, TGF-beta1 in both fresh and lyophilized PRF, while the expression of PDGF-BB, IL-1, TNF, TGF-beta1 has no statistical difference between them (P > .05) but that of IL-4 in Ly-PRF is statistically higher than in fresh PRF (P < .05). When applied in GBR operations, there were no significant differences between Ly-PRF and FPRF in factors of histological and clinical evaluations (i.e., color, swelling, bleeding of the mucosa, pain leveland, and remodeling of hard tissue) performed 3 days, 7 days, and 4 months after the surgery (P > .05). CONCLUSIONS: This study strongly supports that lyophilization at -196 degrees C does not largely influence the expression of bioactive factors, the microstructure of fibrinogen or the clinical effects of PRF.

Expansion of CD11b(+)Ly-6C(+) myeloid-derived suppressor cells (MDSCs) driven by galectin-9 attenuates CVB3-induced myocarditis.[Pubmed:28110209]

Mol Immunol. 2017 Mar;83:62-71.

Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11b(+)Ly-6C(+) myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11b(+)Ly-6C(+) MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C(+) MDSCs, but not Ly6G(+) cells, expressed Arg-1 and NOS2, and suppressed CD4(+) T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l-arginine. Furthermore, Ly6C(+) MDSCs co-expressed higher levels of F4/80, Tim-3, and IL-4Ralpha, and had the plasticity to up-regulate NOS2 or Arg-1 in response to IFN-gamma or IL-4 treatment. The present results indicate that galectin-9 expands CD11b(+)Ly-6C(+) MDSCs to ameliorate CVB3-induced myocarditis.

Short-term dabigatran interruption before cardiac rhythm device implantation: multi-centre experience from the RE-LY trial.[Pubmed:28339794]

Europace. 2017 Oct 1;19(10):1630-1636.

Aims: Cardiac implantable electronic device (CIED) surgery is commonly performed in patients with atrial fibrillation (AF). The current analysis was undertaken to compare peri-operative anticoagulation management, bleeding, and thrombotic events in AF patients treated with dabigatran vs. warfarin. Methods and results: This study included 611 patients treated with dabigatran vs. warfarin who underwent CIED surgery during the RE-LY trial. Among 201 warfarin-treated patients, warfarin was interrupted a median of 144 (inter-quartile range, IQR: 120-216) h, and 37 (18.4%) patients underwent heparin bridging. In dabigatran-treated patients (216 on 110 mg bid and 194 on 150 mg bid), the duration of dabigatran interruption was a median of 96 (IQR: 61-158) h. Pocket hematomas occurred in 9 (2.20%) patients on dabigatran and 8 (3.98%) patients on warfarin (P = 0.218). The occurrence of pocket hematomas was lower with dabigatran compared with warfarin with heparin bridging (RD: -8.62%, 95% CI: -24.15 to - 0.51%, P = 0.034) but not when compared with warfarin with no bridging (P = 0.880). Ischemic stroke occurred in 2 (0.3%) patients; one in the warfarin group (without bridging) and one in the dabigatran 150 mg bid group (P = 0.735). Conclusion: In patients treated with dabigatran undergoing CIED surgery, interruption of dabigatran is associated with similar or lower incidence of pocket hematoma, when compared with warfarin interruption without or with heparin bridging, respectively. Whether uninterrupted dabigatran can reduce pocket hematoma or ischemic stroke remains to be evaluated.

The influence of guanyl nucleotide on agonist and antagonist affinity at guinea-pig CCK-B/gastrin receptors: binding studies using [3H]PD140376.[Pubmed:8876034]

Regul Pept. 1996 Aug 27;65(1):37-43.

The novel radioligand [3H]PD140376 was used to label receptors that bind cholecystokinin (CCK) and related peptides in membranes prepared from guinea-pig brain and gastric glands. Under control conditions, measurements of the apparent affinity of 11 agonist and 16 antagonist ligands in both tissues revealed a strong positive relationship between the affinity of a compound in either tissue (slope of the regression line = 0.89, r2 = 0.908). Agonists consistently showed higher affinity for sites in gastric glands compared to brain. If agonists were excluded from the analysis, the degree of correspondence between affinities measured in each tissue was almost perfect (slope = 0.93, r2 = 0.986). In the presence of the guanyl nucleotide 5'-guanylimidodiphosphate (GppNHp), agonist affinity in gastric glands, but not brain, was reduced such that there was a direct relationship between binding affinity in each tissue. These data are consistent with the notion that the receptor sites in brain and gastric glands, which recognise CCK and gastrin related compounds, are the same and of the CCK-B/gastrin subtype. The receptors in the two respective tissues, however, do appear to differ in the degree of post-receptor coupling. These findings may explain previously reported differences between gastrin and CCK-B receptors that were based upon binding studies using agonist ligands.