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Mechanisms of Chronic Glomerular Injury
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Grone et al.58 have recently reported that in rats fed a high-fat and -cholesterol diet, the incidence of glomerulosclerosis increased significantly. Glomerulosclerosis induced by a high-fat diet was aggravated by unilateral nephrectomy and systemic arterial hypertension, suggesting that altered glomerular hemodynamics may contribute to the sclerotic process in cholesterol fed animals.58 However, it remains unclear whether or not hypercholesterolemia directly perturbs the glomerular microcirculation. Kasiske et al.59,60 have shown that clofibric acid given to rats with 5/6 nephrectomy59 and to hyperlipidemic obese Zucker rats60 lowered both the serum cholesterol and urine albumin excretion rate without significantly altering SNGFR or the glomerular capillary hydraulic pressure. Additionally, mevinolin, a specific pharmacologic inhibitor of HMG-CoA reductase, given to the hyperlipidemic obese Zucker rats60 reduced both the serum cholesterol and triglycerides in these animals, but did not affect glomerular hemodynamic factors.
Pitfalls and Practical Solutions
Published in Joseph Chamberlain, The Analysis of Drugs in Biological Fluids, 2018
The problem of artifactual formation can be greatest in forensic toxicology or in screening methods, where it is necessary to use fairly forcing conditions to take in a wide spectrum of possible compounds. Thus, the conditions routinely used in analytical toxicology have been shown to convert clofibric acid to the amide.1485 The effects of phosgene in chloroform or dichloromethane used for extraction have already been mentioned as a cause of artifactual formation of carbamates of tricyclic antidepressants.1397
The influence of physicochemical properties on the reactivity and stability of acyl glucuronides†
Published in Xenobiotica, 2018
Patrick Camilleri, Akshay Buch, Brandi Soldo, Andrew J. Hutt
Gemfibrozil acyl glucuronide (24) is another example where di-substitution on the α-carbon atom results in increased stability. However, it is noteworthy that the half-life of gemfibrozil acyl glucuronide is about six times longer than that of clofibric acid acyl glucuronide (25), despite the fact that in both cases the α-carbon has two methyl substituents (Spahn-Lanngguth et al., 2007). This substantial difference in stability is presumably due to the electron withdrawing influence (inductive effect) of the phenoxy group on (25) which is further enhanced by the electron withdrawing para-chlorophenyl ring system. The pKa values of the carboxylic acid group in the parent drugs, gemfibrozil and clofibric acid, have been measured as 4.7 and 3.5, respectively. The lower pKa of clofibric acid is a good indication of the more positive nature of the carbon of the carbonyl group in both the acid and the acyl glucuronide (25). On the other hand, the phenoxy group in gemfibrozil acyl glucuronide (24) is too far to exert effective electronic influence on the decomposition of this compound.
Impact of fibrates on circulating cystatin C levels: a systematic review and meta-analysis of clinical trials
Published in Annals of Medicine, 2018
Amirhossein Sahebkar, Luis E. Simental-Mendía, Matteo Pirro, Fabrizio Montecucco, Federico Carbone, Maciej Banach, George E. Barreto, Alexandra E. Butler
This study was designed in accordance with the instructions of the 2009 preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases were searched using the following search terms in titles and abstracts: (fenofibrate OR pemafibrate OR bezafibrate OR clofibrate OR ciprofibrate OR gemfibrozil OR “fibric acid” OR “clofibric acid” OR procetofen) AND (“cystatin C” OR cystatinC). The wild-card term “*” was used to increase the sensitivity of the search strategy. The search was limited to studies in humans. The literature was searched from inception to 2 April 2018.
Stenotrophomonas maltophilia biofilm: its role in infectious diseases
Published in Expert Review of Anti-infective Therapy, 2019
Samantha Flores-Treviño, Paola Bocanegra-Ibarias, Adrián Camacho-Ortiz, Rayo Morfín-Otero, Humberto Antonio Salazar-Sesatty, Elvira Garza-González
Clofibric acid (CA), a naturally occurring lipid regulator found in surface, ground, and drinking water, causes the formation of S. maltophilia biofilms with higher tolerance to chlorine disinfection after prolonged CA exposure (0.17–17 µg/L). In addition, CA exposure changed S. maltophilia susceptibility to antibiotics (e.g. increasing tolerance to erythromycin) and slightly reduced its ability to invade human intestinal cells [106].