The healing effect of topical tea tree oil on pressure ulcers in a rat model.

Objective: The effects of topical tea tree oil (TTO) on the healing of pressure ulcers (PUs) in an animal model was evaluated. Method: To induce PUs, ischaemia-reperfusion cycles were performed by the external application of magnetic plates, with an ischaemic period of eight hours and a reperfusion period of 16 hours. Male and female Wistar rats were divided into three equally sized groups (n=20): one group received topical glycerin twice daily, another group received topical 10% (volume/volume (v/v)) TTO in glycerin twice daily; and the remaining group was untreated. The animals were assessed after one, four, seven and 14 cycles of ischaemia-reperfusion by thermal camera imaging, and then euthanised and sampled to investigate the degree of inflammation, collagen synthesis and apoptosis in the PUs. Results: Although topical glycerin alone suppressed local inflammation and apoptosis, this suppressive effect was accentuated at all timepoints by the application of topical TTO + glycerin. Similarly, an increase in collagen synthesis was observed in the glycerin group and this was accentuated by TTO at all timepoints. Parallel to the histological findings, the local temperature had decreased significantly on days 4 and 7 for both treatment groups (glycerin and TTO+glycerin). Conclusion: In this study, treatment with 10% (v/v) TTO in glycerin effectively suppressed skin inflammation and apoptosis, while it increased collagen synthesis during PU formation.

Design and development of a self-microemulsifying drug delivery system of olmesartan medoxomil for enhanced bioavailability.

Olmesartan medoxomil (OM) is a hydrophobic antihypertensive drug with low bioavailability (26%) and is known to have adverse effects such as celiac disease and enteropathy. The purpose of this study was to develop SMEDDS to increase bioavailability and decrease potential side effects of OM. Hydrophilic lipophilic balance was calculated by testing solubility of OM in different oils, surfactants, and cosurfactants to obtain the most suitable combination of SMEDDS. Pseudoternary phase diagram was used to select the better oil/water formulation of SMEDDS. After a test for 3-month stability, dissolution tests and parallel artificial membrane permeability assay (PAMPA) were conducted to investigate drug solubility and permeability. Biodistribution of fluorescent marked SMEDDS was observed by using in vivo imaging system. The pharmacodynamics of the drug were determined by measuring blood pressure from tails of rats. At the end of the experiment, intestines were examined for adverse effects of OM. Compared with tablet formulation according to the dissolution study, SMEDDS formulation showed 1.67 times improvement in solubility of OM. PAMPA studies suggested a much faster permeability rate for OM SMEDDS compared to the suspension form. Labeled SMEDDS gave 3.96 times stronger fluorescent emission than control dye administered mice in in vivo imaging system (IVIS®) studies, indicating an increased bioavailability. Treating effect of SMEDDS was 3.1 times more efficient compared to suspension in hypertensive rats. It caused neither celiac-like enteropathy nor diarrhea, during 21-day noninvasive blood pressure system (NIBP) assay. Our results suggest that SMEEDS formulation improves dissolution and oral bioavailability of OM while reducing its adverse effects.

[Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia-reperfusion injury in rats]. / Efeitos de dexmedetomidina em conjunto com o pré-condicionamento isquêmico remoto em lesão de isquemia-reperfusão renal em ratos.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the effects of remote ischemic preconditioning by brief ischemia of unilateral hind limb when combined with dexmedetomidine on renal ischemia-reperfusion injury by histopathology and active caspase-3 immunoreactivity in rats. METHODS: 28 Wistar albino male rats were divided into 4 groups. Group I (Sham, n=7): Laparotomy and renal pedicle dissection were performed at 65th minute of anesthesia and the rats were observed under anesthesia for 130min. Group II (ischemia-reperfusion, n=7): At 65th minute of anesthesia bilateral renal pedicles were clamped. After 60min ischemia 24h of reperfusion was performed. Group III (ischemia-reperfusion+dexmedetomidine, n=7): At the fifth minute of reperfusion (100µg/kg intra-peritoneal) dexmedetomidine was administered with ischemia-reperfusion group. Reperfusion lasted 24h. Group IV (ischemia-reperfusion+remote ischemic preconditioning+dexmedetomidine, n=7): After laparotomy, three cycles of ischemic preconditioning (10min ischemia and 10min reperfusion) were applied to the left hind limb and after 5min with group III. RESULTS: Histopathological injury scores and active caspase-3 immunoreactivity were significantly lower in the Sham group compared to the other groups. Histopathological injury scores in groups III and IV were significantly lower than group II (p=0.03 and p=0.05). Active caspase-3 immunoreactivity was significantly lower in the group IV than group II (p=0.01) and there was no significant difference between group II and group III (p=0.06). CONCLUSIONS: Pharmacologic conditioning with dexmedetomidine and remote ischemic preconditioning when combined with dexmedetomidine significantly decreases renal ischemia-reperfusion injury histomorphologically. Combined use of two methods prevents apoptosis via active caspase-3.

Lipopolysaccharide-preconditioning protects against endotoxin-induced white matter injury in the neonatal rat brain.

BACKGROUND: Exposing the brain to a sub-damaging stimulus can protect against a subsequent lethal insult, a phenomenon termed preconditioning. The aim of this study was to investigate the neuroprotective effect of low dose LPS (lipopolysaccharide) pretreatment in endotoxin induced periventricular leukomalacia (PVL) in a rat model. METHODS: Wistar rats with dated pregnancies were allocated to 5 groups: (i) no LPS administered, intraperitoneally (i.p.) pyrogen-free saline injected (Control group), (ii) 500µg/kg LPS administrated i.p. on days 18 and 19 (PVL group), (iii) 50µg/kg LPS administrated i.p. on day 17 followed by 500µg/kg LPS i.p. on days 18 and 19 (PC-PVL group), (iv) 50µg/kg LPS administrated on day 17 (PC only), and (v) i.p. pyrogen-free saline injected control group on day 17. RESULTS: LPS-preconditioning given 24h before potent LPS exposure significantly reduced the number of apoptotic cell deaths and prevented hypomyelination. Antioxidant enzyme gene expression levels (Superoxide Dismutase-SOD1, SOD2, and SOD3) were increased and Tumor Necrosis Factor (TNF)α expression levels were decreased in the PC+PVL group when compared with the PVL group. CONCLUSION: Low-dose LPS given one day before potent doses of LPS reduces antepartum LPS-induced brain damage. The mechanisms of protection might involve oxidation and inflammation.