Serum UPLC-MS/MS Metabolic Profiling in an Experimental Model for Acute-Liver Injury Reveals Potential Biomarkers for Hepatotoxicity.

Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver injury reveals potential biomarkers for hepatotoxicity.

Filed under: Drug and Alcohol Rehabilitation

Metabolomics. 2012; 8(6): 997-1011
Gonzalez E, van Liempd S, Conde-Vancells J, Gutierrez-de Juan V, Perez-Cormenzana M, Mayo R, Berisa A, Alonso C, Marquez CA, Barr J, Lu SC, Mato JM, Falcon-Perez JM

A key interest in clinical diagnosis and pharmaceutical industry is to have a repertoire of noninvasive biomarkers to-individually or in combination-be able to infer or predict the degree of liver injury caused by pathological conditions or drugs. Metabolomics-a comprehensive study of global metabolites-has become a highly sensitive and powerful tool for biomarker discovery thanks to recent technological advances. An ultra-performance liquid chromatography/time-of-flight tandem mass spectrometry (UPLC/TOF MS/MS)-based metabolomics approach was employed to investigate sera from galactosamine-treated rats to find potential biomarkers for acute liver injury. Hepatic damage was quantified by determining serum transaminase activity and in situ liver histological lesions. Principal component analysis in combination with coefficient of correlation analysis was used for biomarker selection and identification. According to the data, serum levels of several metabolites including glucose, amino acids, and membrane lipids were significantly modified, some of them showing a high correlation with the degree of liver damage determined by histological examination of the livers. In conclusion, this study supports that UPLC-MS/MS based serum metabolomics in experimental animal models could be a powerful approach to search for biomarkers for drug- or disease-induced liver injury.
HubMed – drug

Gemcitabine-loaded liposomes: rationale, potentialities and future perspectives.

Filed under: Drug and Alcohol Rehabilitation

Int J Nanomedicine. 2012; 7: 5423-36
Federico C, Morittu VM, Britti D, Trapasso E, Cosco D

This review describes the strategies used in recent years to improve the biopharmaceutical properties of gemcitabine, a nucleoside analog deoxycytidine antimetabolite characterized by activity against many kinds of tumors, by means of liposomal devices. The main limitation of using this active compound is the rapid inactivation of deoxycytidine deaminase following administration in vivo. Consequently, different strategies based on its encapsulation/complexation in innovative vesicular colloidal carriers have been investigated, with interesting results in terms of increased pharmacological activity, plasma half-life, and tumor localization, in addition to decreased side effects. This review focuses on the specific approaches used, based on the encapsulation of gemcitabine in liposomes, with particular attention to the results obtained during the last 5 years. These approaches represent a valid starting point in the attempt to obtain a novel, commercializable drug formulation as already achieved for liposomal doxorubicin (Doxil(®), Caelyx(®)).
HubMed – drug

Penehyclidine hydrochloride: a potential drug for treating COPD by attenuating Toll-like receptors.

Filed under: Drug and Alcohol Rehabilitation

Drug Des Devel Ther. 2012; 6: 317-22
Xiao HT, Liao Z, Tong RS

The aim of this review was to evaluate and summarize the available scientific information on penehyclidine hydrochloride (PHC) for the treatment of chronic obstructive pulmonary disease (COPD) as a result of its ability to attenuate Toll-like receptors. Penehyclidine hydrochloride is an anticholinergic drug manufactured in China, with both antimuscarinic and antinicotinic activity. PHC is used widely in the clinic as a reversal agent in cases of organic phosphorus poisoning and soman poisoning, but also may also have an important role as a bronchodilator in the treatment of obstructive airway disease, including asthma and, in particular, COPD.Our bibliographic sources included the CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS, and CNKI databases, updated to September 2012. In order to assess the data in detail, we used the search terms “penehyclidine hydrochloride,” “COPD,” “muscarinic receptor,” and “toll-like receptors.” Papers were restricted to those published in the English and Chinese languages, and to “paper” and “review” as the document type. Patents were also reviewed.Our survey mainly yielded the results of research on PHC and the mechanisms of COPD. COPD is a preventable and treatable disease with some significant extrapulmonary manifestations that may contribute to its severity in some patients. Recently, it has been shown that muscarinic receptors may interact with Toll-like receptors. Basic and clinical studies of the relationship between the mechanism of action and the effects of PHC in the respiratory tract have been studied by a number of laboratories and institutions. The main advantages of PHC are that it has few M(2) receptor-associated cardiovascular side effects and attenuates Toll-like receptors.PHC may be a promising candidate agent in the treatment of COPD in the future because of its ability to attenuate Toll-like receptors. This review should be of help to those intending to research this topic further.
HubMed – drug

Second Genesis on ABC – Second Genesis is a nonprofit drug and alcohol rehabilitation program with residential treatment centers in Maryland and Washington DC. The mission of Second Genesis is to empower individuals and families to make choices that will enable them to experience healthy, responsible lives free from alcohol, drugs, crime, violence and exploitation. A delegation of 11 women and 1 man from Afghanistan, including doctors, nurses and social workers chose to visit Second Genesis to study best practices in the field of women’s addiction treatment so they can return to their country and improve the quality of care for women in addiction programs. ABC (WJLA News 7) covered this story.

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