The aim of the study was to prepare enrofloxacin nanosuspension injection and evaluate its pharmacokinetics after giving a single intramuscular injection.The high pressure homogeneous technique was used to prepare enrofloxacin nanosuspension injection and preliminary evaluation of the quality was done.The high performance liquid chromatography (HPLC) method was used to determinate content of enrofloxacin in pig plasma.And the pharmacokinetic characteristics of enrofloxacin nanosuspension injection were compared with Baytril injection.The content of enrofloxacin in this preparation is 97.9％.The average particle size of enrofloxacin nanosuspension injection was (613.21±5.78) nm,PDI was (0.22±0.02) and the potential was-2.02 mV.Maximal plasma concentrations were (0.32±0.12) and (0.67 ± 0.09) mg/L after i.m administration with enrofloxacin nanosuspension injection and Baytril injection.The peak times were (2.88 ±0.96) and (0.79±0.26) hours,respectively.Mean elimination half-lifes were (5.99± 1.37) and (4.49 ± 1.25) hours,respectively.Areas under concentration-time curve were (4.63±1.30) and (4.40±0.45) mg/L · h,respectively.Mean residence times were (9.59±2.34) and (5.41±1.10) hours,respectively.The relative bioavailability of enrofloxacin nanosuspension injection was 105.2％.The preparation method of high pressure homogeneous was simple and good reproducibility.Enrofloxacin nanosuspension injection was characterized by non-sedimentation,easy-redispersion,relatively stable.Comparing with Baytril injection,enrofloxacin nanosuspension injection had a certain slowrelease effect,showing slower elimination than enrofloxacin injeetion.

In recent years,studies have shown that inflammation is an important factor in secondaryischemic injury.The exploration of the related mechanisms of the occurrence of inflammation has become ahot spot in the field of cerebral ischemia.Toll-like receptor 4 (TLR4) signaling pathway is one of theclassical inflammatory pathways.Studies have shown that TLR4 is involved in the early inflammatoryresponse after cerebral ischemic injury and the late nerve repair.This article reviews the research progress ofthis signaling pathway in cerebral ischemia injury,so as to seek a therapeutic target against inflammatoryinjury caused by cerebral ischemia through the analysis of its potential research direction.

OBJECTIVETo investigate the transcriptional regulation of pacemaker channel I(f) mediated by vasoactive peptide endothelin-1 (ET-1) in neonatal rat ventricular myocytes and its mechanism.

METHODSNeonatal rat ventricular myocytes were enzymatically isolated. I(f) current was recorded using the whole-cell patch-clamp technique. The expression of hyperpolarization-activated cyclic nucleotide-gated channel (HCN) isoforms HCN2 and HCN4 were measured by quantitative RT-PCR.

RESULTSET-1 increased the expression of HCN2 and HCN4 mRNA in a dose- and time-dependent manner. These effects were blocked by specific ETA receptor antagonist BQ-123 but not the ETB receptor antagonist BQ-788. The effects of ET-1 on HCN2 and HCN4 mRNA expression were not affected by the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB-203580).

CONCLUSIONThese findings indicate that ET-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes via ETA receptor through a p38 MAPK-independent signaling pathway, which might be linked to the intrinsic arrhythmogenic potential of ET-1.

Animals ; Animals, Newborn ; Cyclic Nucleotide-Gated Cation Channels ; drug effects ; Endothelin-1 ; metabolism ; Imidazoles ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Oligopeptides ; pharmacology ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*