Dexmededomidine in pediatric unilateral internal inguinal ring ligation.

BACKGROUND: Safe and effective analgesia strategy remains one of the priorities for pediatric inguinal hernia treatment. AIM: To explore safety and efficacy of dexmededomidine monotherapy for postoperative analgesia in children who received laparoscopic unilateral internal inguinal ring ligation. METHODS: This randomized single-center controlled trial included 390 children (aged 1-3 years, ASA grade I-II), randomly divided into a dexmededomidine group (D group), a dexmededomidine + sufentanil group (DS group), and a sufentanil group (S group). The primary endpoint was percentage of children with the Face, Legs, Activity, Cry, and Consolability (FLACC) score ≤ 3 points 2 h after surgery. RESULTS: The comparisons of the FLACC scores at 2, 4, 6, 8, 12, and 24 h were not significantly different among the three groups (P > 0.05). The sedative effects in the D group were significantly better than those in the S group (P > 0.05), but not significantly different from those in the DS group. The incidence of nausea and vomiting was significantly lower in the D group than in the S group and DS group (P > 0.05). CONCLUSION: Analgesic effects of dexmededomidine monotherapy are comparable to those of sufentanil alone or in combination with dexmededomidine for children who underwent laparoscopic unilateral internal inguinal ring ligation, with better sedative effects and a lower incidence of adverse events.

A novel IL-1RA-PEP fusion protein alleviates blood-brain barrier disruption after ischemia-reperfusion in male rats.

BACKGROUND: Current options to treat clinical relapse in inflammatory central nervous system (CNS) conditions such as cerebral ischemia-reperfusion injury are limited, and agents that are more effective are required. Disruption of the blood-brain barrier is an early feature of lesion formation that correlates with clinical exacerbation and facilitates the entry of inflammatory medium and inflammatory cells. Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring anti-inflammatory antagonist of the interleukin-1 (IL-1) family. The broad-spectrum anti-inflammatory effects of IL-1RA have been investigated against various forms of neuroinflammation. However, the effect of IL-1RA on blood-brain barrier disruption following ischemia-reperfusion has not been reported. METHODS: In this study, we investigated the effects of IL-1RA and a novel protein (IL-1RA-PEP) that was fused to IL-1RA with a cell penetrating peptide, on blood-brain barrier integrity, in male rats subjected to transient middle cerebral artery occlusion. RESULTS: After intravenous administration, IL-1RA-PEP (50 mg/kg) penetrated cerebral tissues more effectively than IL-1RA. Moreover, it preserved blood-brain barrier integrity, attenuated changes in expression and localization of tight junction proteins and matrix metalloproteinases, and enhanced angiogenesis in ischemic brain tissue. Further study suggested that the effects of IL-1RA-PEP on preserving blood-brain barrier integrity might be closely correlated with the p65/NF-κB pathway, as evidenced by the effects of the inhibitor JSH-23. CONCLUSIONS: Collectively, our results demonstrated that IL-1RA-PEP could effectively penetrate the brain of rats with middle cerebral artery occlusion and ameliorate blood-brain barrier disruption. This finding might represent its novel therapeutic potential in the treatment of the cerebral ischemia-reperfusion injury.

A novel IL-1RA-PEP fusion protein with enhanced brain penetration ameliorates cerebral ischemia-reperfusion injury by inhibition of oxidative stress and neuroinflammation.

Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP). Studies were carried out in transient middle cerebral artery occlusion (MCAO) in rats and oxygen glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons. In MCAO rat model, IL-1RA-PEP (50mg/kg) injected i.v., penetrated BBB effectively, and alleviated brain infarction, cerebral edema, neurological deficit score and motor performance as well as inhibited the inflammatory cytokines expression. Furthermore, our results firstly showed that IL-1RA-PEP also regulated the oxidases expression, decreased the levels of NO, MDA and ROS. In addition, the inhibitory effects of IL-1RA-PEP on oxidative stress and inflammation were confirmed in rat cortical neurons induced by OGD/R, it reduced ROS, IL-6 and TNF-α. Further study showed that the effects of IL-1RA-PEP were closely associated with the NF-κB and p38 pathways which were proved respectively by their inhibitors JSH-23 and SB203580. Our results indicated that IL-1RA-PEP could effectively penetrate the brain of MCAO rats, alleviated the cerebral ischemia reperfusion injury by inhibiting neuroinflammation and oxidative stress, showing a great clinical potential for stroke.

Synthesis and antibacterial activity of copper-immobilized membrane comprising grafted poly(4-vinylpyridine) chains.

Poly(4-vinylpyridine) (P4VP) brushes were grafted onto microporous polysulfone (PSF) membranes via surface-initiated atom transfer radical polymerization (SI-ATRP) and then immobilized copper (II) ions on the modified membrane. Copper-loaded membranes exhibited excellent antibacterial properties with the added advantage of repeated use. The chemical composition and surface morphology of the functionalized membrane was characterized by ATR-FTIR, XPS, SEM, and AFM. The results showed that P4VP brushes clustered to rod-shaped covering and the sub-layer of membrane maintained sponge-like structures at the same time. Additionally, the kinetic study of SI-ATRP reaction revealed that the chain length of P4VP brushes increased linearly as the polymerization time increased. The antibacterial effects of copper-loaded CMPSF-g-P4VP membrane against Escherichiacoli were examined and the antibacterial efficiency reached 100% when 2.49wt.% of copper (II) ions was immobilized on membrane. The presented results could serve as a good starting point for the fabrication of antibacterial CMPSF membranes for waste-water treatment applications.