Timing of xenon-induced delayed postconditioning to protect against spinal cord ischaemia-reperfusion injury in rats.

BACKGROUND: This study was designed to assess the neuroprotective effect of xenon-induced delayed postconditioning on spinal cord ischaemia-reperfusion injury (IRI) and to determine the time of administration for best neuroprotection in a rat model of spinal cord IRI. METHODS: Fifty male rats were randomly divided equally into a sham group, control group, and three xenon postconditioning groups (n=10 per group). The control group underwent spinal cord IRI and immediately inhaled 50% nitrogen/50% oxygen for 3 h at the initiation of reperfusion. The three xenon postconditioning groups underwent the same surgical procedure and immediately inhaled 50% xenon/50% oxygen for 3 h at the initiation of reperfusion or 1 and 2 h after reperfusion. The sham operation group underwent the same surgical procedure without aortic occlusion, and inhaled 50% nitrogen/50% oxygen. Neurological function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h of reperfusion. Histological examination was performed using Nissl staining and immunohistochemistry, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling staining. RESULTS: Compared with the control group, the three xenon postconditioning groups showed improvements in neurological outcomes, and had more morphologically normal neurones at 48 h of reperfusion. Apoptotic cell death was reduced and the ratio of Bcl-2/Bax immunoreactivity increased in xenon-treated rats compared with controls. CONCLUSIONS: Xenon postconditioning up to 2 h after reperfusion provided protection against spinal cord IRI in rats, but the greatest neuroprotection occurred with administration of xenon for 1 h at reperfusion.

Post-conditioning by xenon reduces ischaemia-reperfusion injury of the spinal cord in rats.

BACKGROUND: The neuroprotective effects of xenon post-conditioning following spinal cord injury remain unknown. We monitored the effect of xenon post-conditioning on the spinal cord following ischaemia-reperfusion injury and determined its mechanism of action. METHODS: Spinal cord ischaemia was induced following balloon occlusion of the thoracic aorta in male Sprague-Dawley rats. Rats were divided into three groups (n = 30 in each group). The control group underwent ischaemia-reperfusion injury and immediately inhaled 50% (v/v) nitrogen at the time of reperfusion for 60 min continuously. The xenon-post-conditioning group underwent the same surgical procedure and immediately inhaled 50% (v/v) xenon at the time of reperfusion for 60 min continuously. The sham operation group underwent the same surgical procedure without aortic catheter occlusion and inhaled the same gas as that in control rats. Neurologic function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h after reperfusion. Histological changes were observed using Nissl staining, the ultrastructure of the spinal cord was examined using transmission electron microscopy, and apoptosis was monitored using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling. RESULTS: Compared with the control group, the xenon-post-conditioning group showed improved neurologic outcomes (11.3 ± 1.6 vs. 15.7 ± 3.1, respectively) and had more morphologically normal neurons (6 ± 2 vs. 12 ± 3) at 48 h after reperfusion. Moreover, apoptotic cell death in xenon-treated rats was reduced when compared with control rats (18.29 ± 3.06 vs. 27.34 ± 3.63, P < 0.05, respectively). CONCLUSIONS: Xenon post-conditioning exerts a neuroprotective effect on the spinal cord following ischaemia-reperfusion injury via its anti-apoptotic role.

The influence of polymer architecture on the protective effect of novel comb shaped amphiphilic poly(allylamine) against in vitro enzymatic degradation of insulin--towards oral insulin delivery.

Nanocomplexes formed between amphiphilic poly(allylamine) (PAA) and insulin were prepared, characterised and the impact of polymer architecture on the protection of insulin against three enzymes was investigated. PAA previously modified with either cetyl or cholesteryl pendant groups at two levels of hydrophobic grafting and its quaternised derivatives were used to produce polymer-insulin nanocomplexes. Transmittance study, differential scanning calorimetry, hydrodynamic size and zeta potential measurement were conducted and the morphology of the complexes were visualised using transmission electron microscopy. All polymers were found to have an optimal polymer to insulin ratio of 0.4:1 mg mL(-1) with particle size ranging from 88 to 154 nm. Polymer architecture has an impact on the morphology of the complexes produced but has little influence on the complexation efficiency (CE). Almost all polymers were unable to produce complexes with a CE of above 50%. Most polymers demonstrated an ability to reduce insulin degradation by trypsin while the polymer architecture plays a pivotal role against alpha-chymotrypsin and pepsin degradation. Quaternised cholesteryl polymers were able to significantly limit insulin degradation by alpha-chymotrypsin while cetyl polymers were particularly effective against pepsin degradation. These results indicated that a combination of polymers might be required to enhance protection against all three proteolytic enzymes for efficacious oral delivery of insulin.

Regulation of GADD153 induced by mechanical stress in cardiomyocytes.

BACKGROUND: Growth arrest and DNA damage-inducible gene 153 (GADD153), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of GADD153 in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of GADD153 expression and apoptosis induced by mechanical stress in cardiomyocytes. MATERIALS AND METHODS: Aorta-caval shunt was performed in adult Sprague-Dawley rats to induce volume overload. Rat neonatal cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles min(-1). RESULTS: The increased ventricular dimension measured using echocardiography in the shunt group (n = 8) was reversed to normal by treatment with chaperon 4-phenylbutyric acid (PBA) (n = 8) at 500 mg kg(-1) day(-1) orally for 3 days. GADD153 protein and mRNA were up-regulated in the shunt group when compared with sham group (n = 8). Treatment with PBA reversed the protein of GADD153 to the baseline values. The TUNEL assay showed that PBA reduced the apoptosis induced by volume overload. Cyclic stretch significantly increased GADD153 protein and mRNA expression after 14 h of stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA and tumour necrosis factor-alpha (TNF-alpha) antibody 30 min before stretch, reduced the induction of GADD153 protein. Stretch increased, while GADD153-Mut plasmid, SP600125 and TNF-alpha antibody abolished the GADD153 promoter activity induced by stretch. GADD153 mediated apoptosis induced by stretch was reversed by GADD153 siRNA, GADD153-Mut plasmid and PBA. CONCLUSIONS: Mechanical stress enhanced apoptosis and GADD153 expression in cardiomyocytes. Treatment with PBA reversed both GADD153 expression and apoptosis induced by mechanical stress in cardiomyocytes.

The complexation between novel comb shaped amphiphilic polyallylamine and insulin: towards oral insulin delivery.

Novel amphiphilic polyallylamine (PAA) were previously synthesised by randomly grafting palmitoyl pendant groups and subsequent quaternising with methyl iodide. The ability of these self-assembled polymers to spontaneously form nano-complexes with insulin in pH 7.4 Tris buffer was evaluated by transmittance study, hydrodynamic size and zeta potential measurements. The transmission electron microscopy images showed that non-quaternised polymer complexes appeared to form vesicular structures at low polymer:insulin concentrations. However, at higher concentrations they formed solid dense nanoparticles. The presence of quaternary ammonium moieties resulted in insulin complexing on the surface of aggregates. All polymers exhibited high insulin complexation efficiency between 78 and 93%. Incubation with trypsin, alpha-chymotrypsin and pepsin demonstrated that most polymers were able to protect insulin against enzymatic degradation by trypsin and pepsin. Quaternised polymers appeared to have better protective effect against trypsinisation, possibly due to stronger electrostatic interaction with insulin. Interestingly, non-quaternised polymers significantly enhanced insulin degradation by alpha-chymotrypsin. All polymers were less cytotoxic than PAA, with the quaternised polymers exhibiting up to 15-fold improvement in the IC(50) value. Based on these results, quaternised palmitoyl graft polyallylamine polymers showed promising potential as oral delivery systems for insulin.

[Studies on the control of leaf rot disease (Rhizoctonia solani Kuhn) of Amomum compactum Soland ex Maton].

This paper reports the symptoms of leaf rot disease (Rhizoctonia solani) of Amomum compactum and the relationship between the spread of the disease and the conditions of climate. It has been shown that spraying topsine-M before the disease spreads is an effective way to control.