OBJECTIVE: To determine the cardioprotection of adenosine treatment in cadaver donor rats with warm ischemia. METHODS: Rats were randomly divided into 7 groups. Group C was a control group. Group I(5), I(15), and I(30): The donor hearts from the cadaver rats that died of acute hemorrhagic shock and within warm ischemic durations of 5, 15, and 30 min, respectively, and the donor hearts were perfused with STH-1 for 30 min before cervical heterotopic heart transplantation. Group A(5), A(15), and A(30) were adenosine treatment groups and the donor hearts were obtained as mentioned above and perfused with STH-1 plus adenosine (adenosine concentration 1.2 mmol/L) before cervical heterotopic heart transplantation. We detected the change of the grafts including ultrastructure, the level of ATP, SOD, and MDA, NF-kappaB mRNA, TNF-alpha, and IL-6 24 h after the transplantation. RESULTS: At the same time point, compared with Group I(5), I(15), and I(30), Group A(5), A(15), and A(30) showed increased ATP and SOD in the myocardial tissues, and decreased MDA, NF-kappaB mRNA, TNF-alpha, and IL-6 (P<0.05). CONCLUSION Adenosine treatment can protect the graft in cadaver donor rats with warm ischemia. The mechanism may improve the myocardial energy metabolism, attenuate lipid peroxidation injury, suppress the expression of NF-kappaB mRNA, and decrease the inflammatory damage of TNF-alpha and IL-6.
Adenosine ; pharmacology ; Animals ; Cardiotonic Agents ; pharmacology ; Heart ; drug effects ; Heart Transplantation ; Male ; Myocardial Reperfusion Injury ; prevention & control ; Organ Preservation ; methods ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Warm Ischemia ; methods

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl--glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DSPE-PEG) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the tumor penetration and the anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity.