Evaluation and Comparison of Wound Healing Properties of an Ointment (AlpaWash) Containing Brazilian Micronized Propolis and Peucedanum ostruthium Leaf Extract in Skin Ulcer in Rats.

Several previous studies have demonstrated improved wound healing associated with natural-based formulations. Therefore, the purpose of this study was to assess the efficacy of a topical formulation containing both a Brazilian micronized propolis extract and a Peucedanum ostruthium leaf extract for the treatment of wounds created by surgical punch in rats. The study was conducted for 14 days and animals were treated as follows: gauze group (G), polyethylene glycol base ointment (Control), AlpaWash (an ointment containing a Brazilian micronized propolis extract and Peucedanum ostruthium leaf extract [Treatment]), and polysporin (one of the most commonly used topical antibiotic ointments, based on bacitracin zinc and polymyxin B sulfate [Reference Standard]). In general, the results demonstrated that ointments, due to occlusiveness and the ability to maintain moisture under the damaged area, offered improvements when compared to lesions without any treatment. Additionally, the presence of phenolic and flavonoid compounds, as well as antioxidants and antimicrobials, offered improved stimulation and could accelerate wound healing. The Control, Treatment, and Reference Standard groups were able to close the lesion, as measured by the wound healing rate determination and follow-up photographs. However, AlpaWash and Polysporin presented some additional benefits- anti-inflammatory activity, measured using myeloperoxidase and histological count, as well as fibroplasia and hydroxyproline production, suggesting that skin with a better quality could be formed following these two treatments. Therefore, based on the current concern of antibiotic overuse in wound healing, the emergence of multi-resistant organisms and the decrease in newer antibiotics, AlpaWash is considered a prominent formulation to be employed in wound-healing applications.

Influence of experimental diabetes and insulin treatment on the enantioselective pharmacokinetics of mexiletine and its metabolites.

This study evaluates the influence of streptozotocin-induced diabetes on the kinetic disposition and metabolism of mexiletine (MEX) enantiomers in rats. Animals in the control (n = 6 for each blood collection time), diabetic (single intravenous dosage of 45 mg·(kg body mass)(-1) of streptozotocin), and insulin-treated groups (diabetic rats treated daily with 2 IU insulin) received by gavage a single dose of 10 mg·(kg body mass)(-1) racemic MEX. MEX enantiomers and the metabolites hydroxymethylmexiletine (HMM) and p-hydroxymexiletine PHM) were analyzed by LC-MS/MS. Statistical analysis was based on a serial sacrifice design, and parameter estimation was performed using a Bayesian modeling procedure. Area under the curve (AUC) for the (-)-(R) enantiomers of MEX, HMM, and PHM did not differ between the control and diabetic groups. However, AUC for (+)-(S)-MEX and (+)-(S)-HMM were lower in the diabetic than in the control group. Insulin treatment recovered glucose levels to normal and the (+)-(S)-MEX AUC and (+)-(S)-HMM AUC became similar to the AUCs observed in the nondiabetic animals.

Ethanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats.

Chronic ethanol consumption and hypertension are related. In the current study we investigated whether changes in reactivity of the mesenteric arterial bed could account for the increased blood pressure associated with chronic ethanol intake. Changes in reactivity to phenylephrine and acetylcholine were investigated in the perfused mesenteric bed from rats treated with ethanol for 2 or 6 weeks and their age-matched controls. Mild hypertension was observed in chronically ethanol-treated rats. Treatment of rats for 6 weeks induced an increase in the contractile response of endothelium-intact mesenteric bed to phenylephrine, but not denuded rat mesenteric bed. The phenylephrine-induced increase in perfusion pressure was not altered after 2 weeks' treatment with ethanol. Moreover, acetylcholine-induced endothelium-dependent relaxation was reduced by ethanol treatment for 6 weeks, but not 2 weeks. Pre-treatment with indometacin, a cyclooxygenase inhibitor, reduced the maximum effect induced by phenylephrine (Emax) in endothelium-intact mesenteric bed from both control and ethanol-treated rats. No differences in the Emax values for phenylephrine were observed between groups in the presence of indometacin. L-NNA, a nitric oxide (NO) synthase (NOS) inhibitor, increased the Emax for phenylephrine in endothelium-intact mesenteric bed from control rats but not from ethanol-treated rats. Levels of endothelial NOS (eNOS) mRNA were not altered by chronic ethanol consumption. However, chronic ethanol intake strongly reduced eNOS protein levels in the mesenteric bed. This study shows that chronic ethanol consumption increases blood pressure and alters the reactivity of the mesenteric bed. Moreover, the increased vascular response to phenylephrine observed in the mesenteric bed is maintained by two mechanisms: an increased release of endothelial-derived vasoconstrictor prostanoids and a reduced modulatory action of endothelial NO, which seems to be associated with reduced post-transcriptional expression of eNOS.

Effect of ethanol consumption on blood pressure and rat mesenteric arterial bed, aorta and carotid responsiveness.

This study investigates whether chronic ethanol consumption increases blood pressure and alters vascular reactivity in different tissues. Changes in reactivity to phenylephrine and acetylcholine were investigated in the aorta, carotid artery and mesenteric arterial bed (MAB) isolated from rats pretreated with ethanol for 2 or 6 weeks. Mild hypertension was observed in chronically ethanol-treated rats, which was due to rises in both systolic and diastolic pressures. Chronic ethanol consumption increased the contractile response to phenylephrine of endothelium-intact and denuded rat aortic rings from rats pretreated with ethanol for 2 or 6 weeks. Conversely, no differences were found in acetylcholine-induced relaxation. Neither phenylephrine-induced contraction nor acetylcholine-induced relaxation were altered in the rat carotid. Six weeks' ethanol consumption enhanced the contractile response to phenylephrine of endothelium-intact, but not denuded rat MAB. On the other hand, 2 weeks' ethanol consumption did not affect phenylephrine-induced increase in perfusion pressure. Moreover, acetylcholine-induced endothelium-dependent relaxation in the MAB was reduced after treatment with ethanol for 6 weeks but not after 2 weeks. In conclusion, ethanol affects both blood pressure and vessel reactivity, but the effect on vascular reactivity may take longer to become apparent in MAB than in the aorta, and was not evident in the carotid. Moreover, we provide evidence that the effect of ethanol depends on the agonist and blood vessel studied.

Effects of prostanoids on phenylephrine-induced contractions in the mesenteric vascular bed of rats with streptozotocin-induced diabetes mellitus.

The main aim of this study was to compare the vascular reactivity of the perfused (Krebs, 4 ml/min) mesenteric vascular bed (MVB) isolated from rats with streptozotocin (STZ)-induced diabetes of 8 weeks duration to that of the MVB from non-diabetic (ND) Wistar rats. There were no differences in basal perfusion pressure between the MVB isolated from STZ and ND rats. The addition of indomethacin to the perfusate increased the basal perfusion pressure in both ND (18.8 +/- 0.7 vs 29.4 +/- 3.7 mmHg, p < 0.05) and STZ rats (18.3 +/- 0.9 vs 27.2 +/- 2.6 mmHg, p < 0.05), suggesting the release of a vasodilator prostaglandin. Remotion of the endothelium did not affect this response, indicating that prostaglandin was released from vascular smooth muscle. The response to phenylephrine was reduced in STZ rats compared to ND rats (2.3 [1.6-3.8] vs 8.3 [3.5-19.4], ED50. [IC 95%]) and was not modified by removal of the endothelium or by perfusion of L-nitro-arginine (50 microM). In contrast, indomethacin was able to reduce the response to phenylephrine in ND but not in STZ rats (2.3 [1.6-3.8] vs 4.7 [3.2-6.0], ED50. [IC 95%], p=0.02), suggesting that the blunted response to phenylephrine observed in STZ was due to the abolition of the release of prostaglandin by vascular smooth muscle. In conclusion, experimental diabetes induction in the rat is followed by a reduction of the contractile effect of phenylephrine due to the lack of release of a vasoconstrictor prostaglandin from vascular smooth muscle.