The medication discrepancy detection service: A cost-effective multidisciplinary clinical approach.

Objective: To estimate the effectiveness of a Medication Discrepancy Detection Service (MDDS), a collaborative service between the community pharmacy and Primary Care.

Design: Non-controlled before-and-after study.

Setting: Bidasoa Integrated Healthcare Organisation, Gipuzkoa, Spain.

Defining and characterising age-friendly community pharmacies: a qualitative study.

Introduction: The Global Network of Age-friendly Cities is a project promoted by the World Health Organization as a response to demographic ageing and urbanization process. San Sebastian, Spain, is one of these Age-friendly Cities and community pharmacies of the city joined the initiative.

Objective: To define and implement the Age-friendly Pharmacy concept to promote active ageing, optimize the contribution of community pharmacies of San Sebastian to the friendliness of the city and to the improvement of quality of life of the ageing population.

Synthesis and biological evaluation of quinoxaline di-N-oxide derivatives with in vitro trypanocidal activity.

We report the synthesis and in vitro activity against Trypanosoma cruzi epimastigotes of 15 novel quinoxaline derivatives. Ten of the derivatives presented IC50 values lower than the reference drugs Nfx and Bzn; four of them standed out with IC50 values lower than 1.5 μM.

Non-clinical toxicity studies on bioactive compounds within the framework of nutritional and health claims.

The growing presence of products on the market with added value in terms of health makes essential their regulation and harmonization in critical aspects such as safety. The toxicology applied to the bioactive compounds should demonstrate the absence of toxic effects at doses advised for consumption, as well as evaluate the potential toxic effects in the assumption that the products are used in quantities superior to those recommended. The specific strategy should be defined case by case; therefore, prior to any toxicological development, it is essential to study all the information regarding the bioactive compounds (BACs) characterization, nutridynamics and nutrikinetics, that is available.

Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay.

Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) are genotoxic mycotoxins that can contaminate a variety of foodstuffs, the liver and the kidney being their target organs, respectively. The micronucleus (MN) assay (bone marrow) and the comet assay (liver and kidney) were performed simultaneously in F344 rats, treated with AFB1 (0.25 mg/kg b.

Antioxidant and genoprotective effects of spent coffee extracts in human cells.

Spent coffee has been shown as a good source of hydrophilic antioxidant compounds. The ability of two spent coffee extracts rich in caffeoylquinic acids, mainly dicaffeoylquinic acids, and caffeine (Arabica filter and Robusta espresso) to protect against oxidation and DNA damage in human cells (HeLa) was evaluated at short (2 h) and long (24 h) exposure times. Cell viability (MTT) was not affected by spent coffee extracts (>80%) up to 1000 μg/mL after 2 h.

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents.

As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-N-oxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi.

Enhancing the sensitivity of the comet assay as a genotoxicity test, by combining it with bacterial repair enzyme FPG.

The alkaline comet assay, when employed as a genotoxicity test, has relatively low sensitivity because it fails to detect--at non-cytotoxic concentrations--known genotoxins that do not induce breaks or alkali-labile sites. We demonstrate that this limitation is overcome by incorporating in the assay the DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG) to convert damaged bases to breaks. We tested 11 chemicals in human TK-6 cells: three non-cytotoxic--D-mannitol, Tris and EDTA; two cytotoxic--Triton X-100 and fluometuron; and six genotoxic--methylmethanesulphonate (MMS), methylnitrosourea (MNU), cyclophosphamide, benzo(a)pyrene, 4-nitroquinoline-1-oxide (4NQO) and etoposide.

Validation of an antiviral assay method for quantifying IFN-α5 activity in macaque and human serum.

Background: IFN-α5 has been demonstrated to induce stronger signaling and higher expression of antiviral genes than IFN-α2, which is the current treatment in chronic viral hepatitis. However, there is no specific and validated quantification method in order to conduct kinetic studies as part of the preclinical and clinical evaluation for regulatory purposes.

Results: A novel integration of an antiviral assay against the cytopathic effect of the encephalomyocarditis virus in HeLa cells with a very sensitive method for assay processing - the Vialight(®) Plus assay - is presented for IFN-α5 activity quantification.

Kidney and liver distribution of ochratoxin A in male and female F344 rats.

The impact of age and gender on Ochratoxin A (OTA) distribution in kidney and liver were studied. OTA was quantified in kidney and liver of young and mature rats of both sexes. Data was fit simultaneously using the population approach with NONMEM program.

DNA strand cleaving properties and hypoxia-selective cytotoxicity of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide.

The heterocyclic N-oxide, 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, 1), shows promising antitumor activity in preclinical studies, but there is a continuing need to explore new compounds in this general structural category. In the work described here, we examined the properties of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide (9h). We find that 9h causes redox-activated, hypoxia-selective DNA cleavage that mirrors the lead compound, tirapazamine, in both mechanism and potency.

Simple high-performance liquid chromatography-fluorescence detection method for plasma, kidney and liver of rat as a tool for toxicology studies.

A fast and simple HPLC-FLD (high-performance liquid chromatography-fluorescence detection) analytical method has been developed and validated for the determination of ochratoxin A in rat plasma, kidney and liver. The extraction method, calibration curves and chromatographic conditions are common for the three matrices. Plasma and homogenized tissue samples (250 microL) were extracted with ethanol (400 microL) and trichloroacetic acid 20% (w/v) (50 microL).

Gene expression changes induced by ochratoxin A in renal and hepatic tissues of male F344 rat after oral repeated administration.

Ochratoxin A (OTA), a naturally occurring mycotoxin, is nephrotoxic in all animal species tested and is considered a potent renal carcinogen, particularly in male rats. Its mechanism of toxicity is still unknown, although oxidative stress appears to be a plausible mechanism. Therefore, the objective of this study was to identify the biological pathways that are modulated in vivo by OTA in male F344 rats in order to gain further insight into its mechanism of renal toxicity.

A quinoxaline 1,4-di-N-oxide derivative induces DNA oxidative damage not attenuated by vitamin C and E treatment.

Some anticancer compounds are pro-drugs which give rise to toxic species through enzymatic reduction. The quinoxaline-di-N-oxide derivative Q-85 HCl (7-chloro-3-[[(N,N-dimethylamino)propyl]amino]-2-quinoxalinecarbonitrile 1,4-di-N-oxide hydrochloride) is a bioreductive compound selectively toxic in hypoxia. Due to the possibility of secondary tumors the study of the genotoxic capability of antitumoral drugs is very important.

In vitro gene expression data supporting a DNA non-reactive genotoxic mechanism for ochratoxin A.

Ochratoxin A (OTA) is a mycotoxin often found in cereals and agricultural products. There is unequivocal evidence of renal carcinogenicity of OTA in male rats, although the mechanism of action is unknown. At present, available data support an epigenetic mechanism (DNA non-reactive) resulting from oxidative stress and cytotoxicity, because a direct OTA interaction with DNA has not been demonstrated.

Oxidative DNA damage induced by Ochratoxin A in the HK-2 human kidney cell line: evidence of the relationship with cytotoxicity.

Ochratoxin A (OTA) is a mycotoxin produced by species of the genera Aspergillus and Penicillium. The kidneys are the target organ of this mycotoxin and it is considered a potent renal carcinogen in male rats. The mechanisms of its genotoxicity and carcinogenicity have been studied thoroughly, but controversial results have been published.