Purpose: We designed an experimental model of renal ischemia-reperfusion to evaluate the preemptive effect of intravenous sildenafil according to the dose administered (0.7 vs 1.4 mg/kg) and the time of administration (30 minutes before ischemia or during ischemia).
Materials And Methods: A total of 20 minipigs were divided into groups of 4 each, including group 1-control, group 2-sildenafil 0.7 mg/kg intravenously 30 minutes before vascular clamping, group 3-sildenafil 0.7 mg/kg intravenously during warm ischemia, group 4-sildenafil 1.4 mg/kg intravenously 30 minutes before vascular clamping and group 5-sildenafil 1.4 mg/kg intravenously during warm ischemia. The ischemia-reperfusion model was applied using laparotomy and right kidney vascular clamping for 30 minutes, followed by unclamping and reperfusion for 45 minutes. Renal vascular flow and systemic mean arterial pressure were recorded for 45 minutes after unclamping. Mean values were compared using Student t test with significance considered at p <0.05.
Results: Sildenafil led to a decrease in arterial pressure compared to that in controls, especially at the dose of 1.4 vs 0.7 mg/kg, including 113.77, 109.76, 106.12, 97.41 and 82.85 mm Hg in groups 1 to 5, respectively. Renal vascular flow was significantly higher in groups 2 and 3 than in groups 1, 4 and 5 (112.82 and 111.33 vs 88.25, 87.91 and 84.37 ml per minute, respectively, p = 0.000).
Conclusions: The effect of intravenous sildenafil as a preemptive drug against the hemodynamic effects of renal ischemia-reperfusion is dose dependent. The 0.7 mg/kg dose significantly increased reperfusion renal vascular flow with a small decrease in arterial pressure compared to the 1.4 mg/kg dose.
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http://dx.doi.org/10.1016/j.juro.2011.03.036 | DOI Listing |
Aust Vet J
January 2025
Melbourne Veterinary School, University of Melbourne, Werribee, Victoria, Australia.
Background: PAPP is widely used in Australia as a potent vertebrate bait, with potential for off-target ingestion and poisoning in domestic dogs. Whilst toxicosis and resulting methaemoglobinaemia is anecdotally known to occur, this is the first description in the literature. This study reports thirteen clinical cases of suspected Para-aminopropiophenone (PAPP) toxicity in dogs, with the aim of describing clinical presentation and current management of toxicosis in this species.
View Article and Find Full Text PDFNutrients
January 2025
School of Pharmacy, Federal University of Bahia, Barão de Jeremoabo Street, Salvador 40170-115, Brazil.
Studies have demonstrated that resveratrol exerts several pharmacological effects. However, the pharmacokinetic parameters are not completely established. This study describes the plasma pharmacokinetics and tissue distribution of resveratrol after administration by different routes and doses in rats.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, Russia.
Inflammation is a physiological response of the immune system to infectious agents or tissue injury, which involves a cascade of vascular and cellular events and the activation of biochemical pathways depending on the type of harmful agent and the stimulus generated. The Kunitz peptide HCIQ2c1 of sea anemone is a strong protease inhibitor and exhibits neuroprotective and analgesic activities. In this study, we investigated the anti-inflammatory potential of HCIQ2c1 in histamine- and lipopolysaccharide (LPS)-activated RAW 264.
View Article and Find Full Text PDFBioorg Chem
January 2025
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, United Kingdom. Electronic address:
Withanone (WN), a bioactive phytochemical isolated from the medicinal herb Withania somnifera, has shown multiple pharmacological and therapeutic successes, including neuroprotective and anti-cancer activities. However, detailed pharmacokinetic (PK) properties of pure WN were not well defined. Pharmacokinetic (PK) characteristics, dose proportionality, and absolute bioavailability of pure WN were explored in rats using an efficient, reliable, and sensitive LC-MS/MS assay to address this gap.
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January 2025
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address:
Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined.
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