The spatiotemporal control of erosion and molecular release from micropatterned poly(ethylene glycol)-based hydrogel

Hydrogels have been extensively studied as a carrier of various hydrophilic molecular compounds and cells for local delivery and subsequent controlled release. One of key design parameters in the hydrogel assembly is an ability to control spatiotemporal gel degradation, in order to tailor release rates of multiple drugs and also regulate phenotypic activities of co-cultured cells. To achieve this goal, this study presents a simple but innovative implantable, microfabricated hydrogel patch that undergoes micropatterned surface erosion at controlled rates and subsequently discharges two molecular compounds of interests at desired rates. This device was prepared by first fabricating a non-degradable poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogel patch containing micro-pockets of controlled spacing and subsequently filling micro-pockets with a hydrogel of poly(ethylene imine) (PEI) and PEG diacrylate (PEGDA) that was tailored to degrade at controlled rates. Separate incorporation of vascular endothelial growth factor (VEGF)121 and VEGF165, known to orchestrate vascular development, into the PEI-PEGDA gel and PEGDMA hydrogel resulted in enhanced neovascularization at the implantation sites due to bimodal, sequential release of two VEGF isoforms. We believe that the hydrogel patch fabricated in this study will be highly useful to better understand a broad array of complex biological processes and also improve the efficacy of molecular cargos in varied applications.     

The relationship between age-related development of spike-and-wave discharges and the resistance to amygdaloid kindling in rats with genetic absence epilepsy

Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are resistant to amygdaloid kindling. Since in GAERS the characteristics of spike-and-wave discharges (SWDs) change with age, we have studied the relation between SWD maturation and the development of kindling resistance. Non-epileptic Wistar rats and GAERS were stimulated in basolateral amygdala with 400 μA at 20 min intervals until they reached stage 5 seizures or for a maximum of 36 stimulations. All of the Wistar rats, the postnatal (PN) day 20 GAERS and the (kindling-prone) subgroups of GAERS at PN30 and PN60 reached stage 5 seizures; at PN20, PN30 and PN60 kindling rates were significantly slower in GAERS compared to Wistar rats. At PN30 and PN60, 41% and 69% of GAERS, respectively, showed no stage 3, 4 or 5 seizures after 36 stimulations (kindling-resistant subgroups). The SWD maturation involves changes in spectral patterns and correlate with age-related increases in kindling resistance in GAERS.     

Effects of heparin on bacterial translocation and gut epithelial apoptosis after burn injury in the rat: dose-dependent inhibition of the complement cascade

This study investigated levels of complement inhibition, apoptosis of gut epithelium, and bacterial translocation (BT) associated with different doses of heparin in rats with severe burns. After burn injury, the animals in Groups 1, 2, 3, and 4 received intravenous tail-vein bolus heparin doses of 150, 300, 600, and 1200 U/kg, respectively. Group 5 received no heparin after burn injury. Group 6 served as control group. According to the results, Group 2 had the highest rate of positive staining for C3, and Group 4 had the lowest rate. There were significant differences between these two groups with respect to distribution of immunoflouresein scores for C3 (p=0.01). Group 5 had the highest mean TUNEL index of all the groups (258/10) (p=0.01). On electron microscopy, the connective tissue cells in the ileal submucosa from Groups 4 and 5 showed more significant apoptotic changes than the corresponding cells in the other groups. The total BT values in Group 4 (129 x 10(4) CFU) and Group 5 (100 x 10(4) CFU) were both significantly higher than those in the other groups (p=0.01). Group 1 had the lowest total BT value (6.1 x 10(2) CFU) (p=0.001). In summary, our results confirm that heparin administration after significant burn injury in rats can reduce BT, and that the effect is related to dose. The findings also indicate that levels of BT after burn injury increase in parallel with the extent of gut epithelial cell apoptosis.     

Association between soluble lectin-like oxidized low-density lipoprotein receptor 1 levels and coronary slow flow phenomenon

Introduction

The coronary slow flow phenomenon (CSFP) has been associated with myocardial ischemia, myocardial infarction, life-threatening arrhythmias, sudden cardiac death and increased cardiovascular mortality similar to coronary artery disease (CAD). Possible underlying mechanisms of CSFP are endothelial dysfunction, chronic inflammation, microvascular dysfunction and diffuse atherosclerosis. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) seems to play an important role in the pathogenesis of atherosclerosis. We hypothesized that sLOX-1 might be associated with CSFP, and aimed to research the relationship between sLOX-1 and CSFP.

Material and methods

Forty patients with angiographically proven CSFP and 43 patients with a normal coronary flow pattern (NCFP) were included in this study. Coronary blood flow was measured according to the Thrombolysis In Myocardial Infarction (TIMI) frame count method. sLOX-1 levels were measured in all study subjects.

Results

Serum levels of sLOX-1 were significantly higher in the CSFP group than the NCFP group (1061.80 ±422.20 ng/ml vs. 500.043 ±282.97 ng/ml, p < 0.001, respectively). Multivariate logistic regression analysis including sLOX-1, MPV, GGT and uric acid levels revealed a significant association between sLOX-1 levels and CSFP (Exp (B)/OR: 1.006, 95% CI: 1.002–1.010, p = 0.001).

Conclusions

The present study demonstrated that serum sLOX-1 levels were significantly higher in patients with CSFP and there was a strong association between high sLOX-1 levels and CSFP. High serum sLOX-1 levels may have an important role in the pathogenesis of CSFP. Future studies are needed to confirm these results.