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Sea urchins play a key role in the marine environment, contributing to maintain a balance in benthic ecosystems. Toxopneustes roseus acts as a regulator of rhodolith beds and is a key species as a bioturbation promoter, while Rhyncholampas pacificus moderates the detritus content of sediment through various mechanisms and contributes to accelerating the circulation of organic matter. However, nothing is known about their early development, so the objective of this research is to characterize the embryonic and larval development of specimens of the two species from the southern Mexican Pacific and identify the causes that produce their differences. The embryonic development of T. roseus lasted approximately 20 ​h; the echinopluteus larva appeared at 23 ​h and culminated in around 12 days with an eight-armed larva. Metamorphosis was reached at 18 days. The embryonic development of R. pacificus lasted about 15 ​h; the larva emerged at 20 ​h and culminated in about two days with an eight-armed larva. The metamorphosis was completed in 9 days. The reproductive output of both species determines their development time and the structure of their larvae; therefore, the energy of R. pacificus is invested in reaching metamorphosis earlier to ensure that its larvae, which are not very abundant, settle and recruit to the population. Regarding T. roseus, the longest permanence in the plankton is efficiently maintained by its numerous larvae through the presence of mobile arms and the shift of the swimming function to the epauletes. This is the first work that characterizes the early development of a species of the genus Toxopneustes and of the only living species of the genus Ryncholampas. The information generated in this work is essential to gaining knowledge about these groups of echinoids, especially the effect of the environment on their early development., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The O-arylcarbamate URB937 is a potent inhibitor of fatty-acid amide hydrolase (FAAH), an intracellular serine hydrolase responsible for the deactivation of the endocannabinoid anandamide. URB937 is unique among FAAH inhibitors in that is actively extruded from the central nervous system (CNS), and therefore increases anandamide levels exclusively in peripheral tissues. Despite its limited distribution, URB937 exhibits marked analgesic properties in rodent models of pain. Pharmacological evidence suggests that the extrusion of URB937 from the CNS may be mediated by the ABC membrane transporter ABCG2 (also called Breast cancer resistance protein, BCRP). In the present study, we show that URB937 is a substrate for both mouse and human orthologues of ABCG2. The relative transport ratios for URB937 in Madin-Darby canine kidney (MDCKII) cells monolayers over-expressing either mouse Abcg2 or human ABCG2 were significantly higher compared to parental monolayers (13.6 and 13.1 vs. 1.5, respectively). Accumulation of the compound in the luminal/apical side was prevented by co-administration of the selective ABCG2 inhibitor, Ko-143. In vivo studies in mice showed that URB937 (25 mg kg(-1)) readily entered the brain and spinal cord of Abcg2-deficient mice following intraperitoneal administration, whereas the same dose of drug remained restricted to peripheral tissues in wild-type mice. By identifying ABCG2 as a transport mechanism responsible for the extrusion of URB937 from the CNS, the present results should facilitate the rational design of novel peripherally restricted FAAH inhibitors., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The present article aims to review the up-to-date information on the most recent studies of the interaction of flavonoids with ABC transporters, in particular the drug pharmacokinetic consequences of such a relationship. In addition, the modulation of the expression of the ABC transporters by flavonoids is also illustrated. Flavonoids are a large group of plant polyphenols present extensively in our daily diets and herbal products. High intake of isoflavones has been associated with a variety of beneficial effects on several common diseases. These polyphenols interact with ABC drug transporters involved in drug resistance and drug absorption, distribution and excretion. A number of studies have demonstrated inhibition of drug transporters by flavonoids. This flavonoid-ABC-transporter interaction could be beneficial for poorly absorbed drugs but could also result in severe drug intoxication, especially drugs with a narrow therapeutic window. On the other hand, flavonoids are themselves substrates of ABC transporters. These proteins can affect the oral availability and tissue distribution of these compounds, modifying their beneficial effects. The challenge is to find a suitable way to predict harmful drug-flavonoid interactions mediated by these transporters., ((c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.)

The study characterizes the interaction between BCRP/ABCG2 and moxidectin by means of cellular transport, and pharmacokinetic studies in Bcrp1 (-/-) and wild-type mice. Milbemycin moxidectin ([(3)H]-moxidectin) was tested for its ability to be transported across MCDK-II epithelial monolayer cultures transfected with BCRP. In a second approach, accumulation assays by BCRP-expressing Xenopus laevis oocytes were carried out. Finally, pharmacokinetic studies were performed in order to establish the role of the transporter in milk secretion and tissue distribution. The efflux was negligible in polarized cells but moxidectin was efficiently transported in BCRP-expressing X. laevis oocytes. The transport was blocked by an acridone derivative, a novel BCRP inhibitor. Moxidectin secretion into breast milk was decreased in Bcrp1-knockout mice and the milk to plasma ratio was 2-fold higher in wild-type mice after i.v. administration. Drug accumulation in intestinal content, bile, and intestine was higher in wild-type mice but the plasma concentration was not different. Moxidectin is identified as a BCRP substrate since its Bcrp1-mediated secretion into breast milk and the involvement of Bcrp1 in intestinal and bile secretion has been demonstrated. This interaction has pharmacokinetic and toxicological consequences. The most important toxicological consequences of the interaction between BCRP and moxidectin may be related with the presence of drug residues in milk.

Quinolones and fluoroquinolones are broad spectrum bactericidal drugs, which are widely used in both human and veterinary medicine. These drugs can quite easily enter cells and are often used to treat intracellular pathogens. Some fluoroquinolones have been reported to undergo efflux, which could explain their low bioavailability. There is a growing need to understand resistance mechanisms to quinolones, involving for instance mutations or the action of efflux pumps. Several members of the ATP-binding cassette (ABC) drug efflux transporter family (MDR, MRP, ABCG2) significantly affect the pharmacokinetic disposition of quinolones. Active secretory mechanisms common to all fluoroquinolones have been suggested, as well as competition between fluoroquinolones at transporter sites. For grepafloxacin and its metabolites, MRP2 has been demonstrated to mediate biliary excretion. However, MDR1 is responsible for grepafloxacin intestinal secretion. Recently it has been shown that ciprofloxacin and enrofloxacin are efficiently transported ABCG2 substrates which are actively secreted into milk. It appears that multiple ABC transporters contribute to the overall secretion of fluoroquinolones. The objective of this work is to review the recent advances in insights into ABC transporters and their effects on fluoroquinolone disposition and resistance including data on drug secretion into milk.

Hyaluronan (HA) was depolymerized by hydroxyl radicals generated from hydrogen peroxide and cupric ions. Inhibition of HA degradation by four well-known antioxidants was investigated, as HA can scavenge reactive oxygen species (ROS). Change in hyaluronan molecular weight was observed by size-exclusion chromatography. Inhibition of HA degradation was estimated from the retention times observed. It was found that HA degradation was inhibited in a clearly concentration-dependent manner by mannitol, thiourea and vinpocetine. Propofol also inhibited the depolymerization, but its concentration-dependent effect was not so clear. The antioxidant concentrations at which HA degradation was decreased by 50% were 42 microM for thiourea; 1.35 microM for vinpocetine; and 0.39 microM for propofol. A concentration of 26.51 mM of mannitol was needed to attain the same inhibitory effect. Although many factors are involved in a therapeutic response, the results obtained in this study support the idea that HA may be protected from ROS attack by the concomitant use of well-known antioxidants.

Intestinal ischemia-reperfusion (I/R) is a serious clinical condition that triggers a complex inflammatory response. Inflammatory processes affect some enzymatic systems related to intestinal drug metabolism and bioavailability. Diltiazem (DTZ) is a calcium channel blocker, which is extensively metabolised in the intestine by esterases and different CYP450 isoforms. The main biotransformation pathway of DTZ in rats is desacetylation by esterases. This study analysed the effect of I/R on intestinal absorption and metabolism of DTZ, focusing on esterase activity, through different methodologies, after 60 min of superior mesenteric artery occlusion and 30 min of reperfusion or sham surgical procedures. The rate of DTZ appearance in blood during in situ studies increased significantly in the I/R group (0.094+/-0.014 10(-5) cm/s vs 0.271+/-0.110 10(-5) cm/s) and the calculated metabolised fraction of DTZ decreased significantly, showing an important reduction in the desacetylase activity in the I/R group. These results were supported by microsomal incubations, where desacetylase activity was related to esterases by specific inhibition, using paraoxon and bis-nitrophenylphosphate, and also by studies in everted rings. DTZ metabolism was higher in the jejunum than in the ileum, the esterase activity being affected by I/R in both regions. The present findings suggest that I/R injury clearly affects the esterases' activity and modifies the amount of DTZ and its metabolites in blood during in situ perfusion. This modification of intestinal esterase activity could be important for the pharmacokinetic behaviour of other drugs and prodrugs after intestinal pathologies involving inflammation and oxidative stress.

Depolymerisation by oxytetracycline (OTC) as well as the progressive cleavage of hyaluronic acid induced by ultrasound was investigated in nine commercially available hyaluronic polymers. Sample solutions differed in molecular weight, from 500 to 7000 kDa, and in their source. The hyaluronic acid concentration in each sample was analysed by HPLC. The concentration range was over 8.39-10.18 mg ml(-1) in samples with a nominal concentration of 1%, and 14.05 mg ml(-1) in one sample with a nominal concentration of 1.5%. It was found that stability was dependent on both molecular weight and the concentration of the samples. The rheological parameters n (power law index) and K (consistency coefficient) were good predictors regarding the degradation behaviour. Although many factors are involved in obtaining a therapeutic response, the results obtained in this work support the notion that both mechanical and chemical degradation are reduced in hyaluronate solutions with low molecular weight, the final concentration of the product being a critical factor.

The aim of this study was to investigate the interactive effects of exercise training and chronic ethanol consumption on metabolism, capillarity, and myofibrillar composition in rat limb muscles. Male Wistar rats were treated in separate groups as follows: non exercised-control; ethanol (15%) in animals' drinking water for 12 weeks; exercise training in treadmill and ethanol administration plus exercise for 12 weeks. Ethanol administration decreased capillarity and increased piruvate kinase and lactate dehydrogenase activities in white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase activity and decreased cross-sectional area of type I, IIa, and IIb fibres. Exercise increased capillarity in all four limb muscles and decreased type I fibre area in plantaris. The decreased capillarity effect induced by ethanol in some muscles, was ameliorated when alcohol was combined with exercise. While alcoholic myopathy affects predominantly type IIb fibres, ethanol administration and aerobic exercise in some cases can affect type I and type IIa fibre areas. The exercise can decrease some harmful effects produced by ethanol in the muscle, including the decrease in the fibre area and capillary density.

The effect of ethanol administration on gastric absorption in rats of two benzimidazole derivatives has been studied. The ethanol administration was carried out as both acute (5%, 10% and 15% w/v of ethanol in the perfusion solution), and chronic (15, 30 and 120 days) forms. Two benzimidazole derivatives were used: albendazole (ABZ) and mebendazole (MBZ). The administration of ethanol did not affect the kinetic mechanism of the absorption process (simple diffusion) but the absorption rate decreased in all treatments except in 5% acute ethanol, presumably due to the improved solubility of the drugs. Plasma, bile and liver levels after gastric perfusion suggest a possible interference of ethanol metabolism with drug hepatic metabolism.

The efficacy of albendazole in hydatid disease is still unclear, because there has been no study that assessed the status of the parasite after treatment. The significance of albendazole-induced echographic changes in the cyst therefore cannot be judged. We did a prospective, controlled, randomised, open study of albendazole in patients with liver hydatid disease, and assessed parasite viability after treatment. 18 patients received no albendazole treatment (controls), 18 received albendazole (10 mg/kg daily) for 1 month (group A), and 19 received the drug for about 3 months (group B). Echography was done before and during treatment; all patients underwent surgery on completion. Parasite (protoscolex viability and development of cysts in mice) and ultrastructure studies were done for all cysts removed. 8 (50%) of cysts in the control group, 13 (72%) in group A, and 16 (94%) in group B were non-viable (p = 0.015). Protoscolex and cyst viability were significantly (p = 0.039 and p = 0.018, respectively) lower in treated patients than in controls. Treatment was also significantly associated with total cyst membrane disintegration. 68% of cysts treated for 3 months showed echographic changes, and only 1 of 20 cysts showing echographic changes during treatment was judged viable. The efficacy of albendazole at a dose of 10 mg/kg daily for 3 months suggests that it is a suitable alternative to surgery in uncomplicated hydatid liver disease, as initial treatment.

Data are presented on the effect of ethanol on the intestinal absorption and excretion in rats of two beta-lactam antibiotics, cephalexin (CFX) and cefadroxil (CFD). A recirculating perfusion technique within an antibiotic concentration range of 0.5 to 50 mM was used. Ethanol was administered either in an acute form into the intestine or in a chronic form as a 15% drinking solution for 2 months. The results are normalized in relation to the metabolic body weight, intestinal length, and osmotic conditions. Acute ethanol treatment decreases the antibiotic absorption; biliary excretion of CFD is increased, while urinary excretion of CFX is lowered. Chronic treatment shows slight negative effects on the absorption of CFX and CFD. Results are interpreted on the basis of the effect of ethanol on biological membranes. Enhanced urinary excretion after acute ethanol treatment, as well as differences between transport mechanisms, are invoked to explain these effects.