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Copyright of Hospital a Domicilio is the property of Centro Internacional Virtual de Investigacion en Nutricion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Drug combination for the treatment of pain is common clinical practice. Co-crystal of Tramadol-Celecoxib (CTC) consists of two active pharmaceutical ingredients (APIs), namely the atypical opioid tramadol and the preferential cyclooxygenase-2 inhibitor celecoxib, at a 1:1 molecular ratio. In this study, a non-formulated ‘raw’ form of CTC administered in suspension (referred to as ctc susp ) was compared with both tramadol and celecoxib alone in a rat plantar incision postoperative pain model. For comparison, the strong opioids morphine and oxycodone, and a tramadol plus acetaminophen combination at a molecular ratio of 1:17 were also tested. Isobolographic analyses showed that ctc susp exerted synergistic mechanical antiallodynic (experimental ED 50 = 2.0 ± 0.5 mg/kg, i.p.; theoretical ED 50 = 3.8 ± 0.4 mg/kg, i.p.) and thermal (experimental ED 50 = 2.3 ± 0.5 mg/kg, i.p.; theoretical ED 50 = 9.8 ± 0.8 mg/kg, i.p.) antihyperalgesic effects in the postoperative pain model. In contrast, the tramadol and acetaminophen combination showed antagonistic effects on both mechanical allodynia and thermal hyperalgesia. No synergies between tramadol and celecoxib on locomotor activity, motor coordination, ulceration potential and gastrointestinal transit were observed after the administration of ctc susp . Overall, rat efficacy and safety data revealed that ctc susp provided synergistic analgesic effects compared with each API alone, without enhancing adverse effects. Moreover, ctc susp showed similar efficacy but improved safety ratio (80, measured as gastrointestinal transit vs postoperative pain ED 50 ratios) compared with the strong opioids morphine (2.5) and oxycodone (5.8). The overall in vivo profile of ctc susp supports the further investigation of CTC in the clinical management of moderate-to-severe acute pain as an alternative to strong opioids. [ABSTRACT FROM AUTHOR]

Pharmacokinetics of cisplatin administered by the pulmonary route were established in mice using dry powders inhaler (DPI) formulations showing immediate (F1) and controlled release (CR, solid lipid microparticles) in vitro, without (F2) or with PEGylated excipients (F3, F4). Formulation administration was realized using dry powder blends (correspondingly named thereafter F1 B to F4 B ) able to reproducibly deliver particles in vivo using a DP-4M Dry Powder Insufflator™. Their platinum pharmacokinetics were established over 48 h in lungs, total blood and non-target organs vs. IV and endotracheal nebulization (EN). EN and F1 B were rapidly distributed from the lungs ( t 1/2 i 2.6 and 5.0 min). F2 B was eliminated in ∼1 h ( t 1/2 i 9.0 min). F3 B lung retention was sustained for ∼7 h ( t 1/2 i 59.9 min), increasing lung AUC 11-, 4- and 3-fold vs. IV, F1 B and F2 B . Total blood t max were higher and AUC and C max lower using the pulmonary route vs. IV. Kidney C max was reduced 6-, 2- and 3-fold for F1 B , F2 B and F3 B . AUC in kidneys were 2- to 3-fold lower for F1 B and F2 B vs. IV but comparable for IV vs. F3 B , probably because of kidney saturation. PEGylated solid lipid microparticles provided cisplatin particles with interesting lung retention and CR properties. [ABSTRACT FROM AUTHOR]

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND AND PURPOSE Dersalazine sodium (DS) is a new chemical entity formed by combining, through an azo bond, a potent platelet activating factor (PAF) antagonist (UR-12715) with 5-aminosalicylic acid (5-ASA). DS has been demonstrated to have anti-inflammatory effects on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats and recently in UC patients in phase II PoC. There is Increasing evidence that Th17 cells have an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to further characterize the anti-inflammatory effects of DS. EXPERIMENTAL APPROACH Effect of DS (10 or 30 mg·kg−1 b.i.d.) on TNBS-induced colitis in rats was studied after 2 and 7 days with special focus on inflammatory mediators. Additionally, its anti-inflammatory properties were analysed in two different models of dextran sodium sulphate (DSS)-induced colitis, BALB/c and C57BL/6 mice, the latter being dependent on IL-17. KEY RESULTS DS, when administered for 7 days, showed intestinal anti-inflammatory effects in TNBS-induced colitis; these effects were observed both macroscopically and through the profile of inflammatory mediators (TNF, IL-1β, IL-6 and IL-17). Although the 2 day treatment with DS did not induce intestinal anti-inflammatory effects, it was sufficient to reduce the enhanced IL-17 expression. DS showed beneficial effects on DSS-induced colitis in C57BL/6 mice and reduced colonic pro-inflammatory cytokines IL-1β, IL-6 and IL-17. In contrast, it did not exert intestinal anti-inflammatory effects on DSS-induced colitis in BALB/c mice. CONCLUSIONS AND IMPLICATIONS DS exerts intestinal anti-inflammatory activity in different rodent models of colitis through down-regulation of IL-17 expression. [ABSTRACT FROM AUTHOR]

Univentricular congenital heart diseases include a range of entities that result in a functionally single ventricular chamber. Although the only curative therapy is cardiac transplantation, there are several palliative surgical techniques that prevent ventricular volume overload, diverting part or all the systemic venous circulation into the pulmonary arteries. The modern Fontan procedure, which consists of anastomosing both the superior (SVC) and inferior vena cava (IVC) to the right pulmonary artery (RPA), is nowadays the last step before transplantation. The importance of imaging in these entities lies not only in the understanding of the new circuit established after surgical correction, but also in the early detection of the wide spectrum of cardiac and extracardiac complications that can occur due to the new physiological condition. Due to the increased survival of these patients, long-term complications are becoming more common. The main cardiac complications are atrial enlargement, ventricular dysfunction, and stenosis or thrombosis of the conduit. Pulmonary artery stenosis, pulmonary arteriovenous fistulae (PAVF), systemic-pulmonary veno venous shunts (VVS), hepatic congestion, cardiac cirrhosis, and protein-losing enteropathy are potential extracardiac complications. [ABSTRACT FROM AUTHOR]

Thesynthesis and pharmacological activity of a new series of hexahydro-2H-pyrano[3,2-c]quinoline derivatives aspotent σ1receptor (σ1R) ligandsare reported. This family, which does not contain the highly basicamino group usually present in other σ1R ligands,showed high selectivity over the σ2receptor (σ2R). The activity was shown to reside in only one of the fourpossible diastereoisomers, which exhibited a perfect match with knownσ1R pharmacophores. A hit to lead program based ona high-throughput screening hit (8a) led to the identificationof compound 32c, with substantially improved activityand physicochemical properties. Compound 32calso exhibiteda good ADMET (absorption, distribution, metabolism, excretion, toxicity)profile and was identified as a σ1R antagonist onthe basis of its analgesic activity in the mouse capsaicin and formalinmodels of neurogenic pain. [ABSTRACT FROM AUTHOR]

Abstract: Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin''s therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose+atorvastatin (30mg/kg/day) Sprague–Dawley rats were sacrificed after 14days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid β-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (×0.74) and liver triglyceride (×0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (×0.45) and its target genes, and increased the hepatic activity of the fatty acid β-oxidation system (×1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (×0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. [Copyright &y& Elsevier]