Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease.     

Análisis y minimización del riesgo de rotura de stock aplicado a la gestión en farmacia hospitalaria

ObjectiveTo determine how many dispensary drugs should be in the safety stock in a tertiary hospital in accordance with the risk level and the number of days that the hospital is able to withstand a stockout.MethodsWe statistically analysed the infliximab order recorded over a period of 120 days. This drug is relevant for this study as it is costly and is immediately supplied to the clinic. Using the data records for purchasing and dispensing in our department, we created a table to compare the level of risk assumed with the number of units in stock and the number of days that the safety stock should last. In addition, we calculated how much stock there should be in accordance with different heuristic rules used by pharmacy departments.ResultsIn the period being studied, the daily order was 11.4 ± 14.8 units of infliximab. Using the methodology proposed, we discovered that there should be 79 units in the safety stock. Other hospital rules determine values of 47 and 119 units.ConclusionsThe method proposed allows us to discover the risk level that is assumed when selecting the safety stock. Therefore, we are able to design a safety stock policy consistent with the risk level adopted. Under certain assumptions the safety stock quota provided by this method could be reduced. Lastly, there is a notable difference between the safety stock values suggested by different rules, as it has been shown in this article.     

Intoxication caused by new psychostimulants: analytical methods to disclose acute and chronic use of benzofurans and ethylphenidate

International Journal of Legal Medicine - The acute and chronic toxicity of several new psychoactive substances (NPS) is unknown, and only little information is available on the pharmacology and...     

Evolución de cirrosis biliar primaria a síndrome de solapamiento con hepatitis autoinmune en paciente con hepatitis B crónica

We describe the case of a female patient with a previous diagnosis of primary biliary cirrhosis (PBC) and chronic hepatitis B in inactive phase who developed increased transaminase levels with no evidence of hepatitis B virus reactivation while receiving ursodeoxycholic acid treatment. A liver biopsy showed changes compatible with overlapping autoimmune hepatitis (AIH). Budesonide treatment achieved normalization of transaminase levels. We provide a review of PBC and AIH overlap syndrome and discuss the particular features of this case that led us to this diagnosis, as well as the treatment provided.     

Molecular Investigation of Tularemia Outbreaks,Spain, 1997–2008

Tularemia outbreaks occurred in northwestern Spain in 1997–1998 and 2007–2008 and affected >1,000 persons. We assessed isolates involved in these outbreaks by using pulsed-field gel electrophoresis with 2 restriction enzymes and multilocus variable number tandem repeat analysis of 16 genomic loci of Francisella tularensis, the cause of this disease. Isolates were divided into 3 pulsotypes by pulsed-field gel electrophoresis and 8 allelic profiles by multilocus variable number tandem repeat analysis. Isolates obtained from the second tularemia outbreak had the same genotypes as isolates obtained from the first outbreak. Both outbreaks were caused by genotypes of genetic subclade B.Br:FTNF002–00, which is widely distributed in countries in central and western Europe. Thus, reemergence of tularemia in Spain was not caused by the reintroduction of exotic strains, but probably by persistence of local reservoirs of infection.