Neurol Clin Pract. 2013 Jun; 3(3): 254-260
Oh J, O’Connor PW

Teriflunomide is a novel disease-modifying agent that was recently approved for use in the treatment of multiple sclerosis (MS). Teriflunomide has demonstrated clinical efficacy and safety in a number of large, multicenter, phase III clinical trials and is an attractive agent to add to the growing repertoire of available treatments for MS, as it has the benefit of oral administration. Furthermore, existing clinical experience with its parent drug, leflunomide, provides indirect long-term safety data. This review summarizes teriflunomide’s pharmacologic properties, pivotal clinical trials, and safety profile, and ends with a discussion of the role of teriflunomide in the context of current and emerging MS treatment options. HubMed – drug

Generic substitution of antiepileptic drugs: What’s a clinician to do?

Neurol Clin Pract. 2013 Apr; 3(2): 161-164
Privitera M

Generic substitution of antiepileptic drugs remains a controversial area without a clear consensus to guide clinicians. The US Food and Drug Administration (FDA) requires rigorous testing of generic products and states that all approved products are interchangeable. FDA studies involve single doses in normal subjects so may not represent the performance of generic products in people with epilepsy. Physician surveys, case reports, and retrospective pharmacy database analyses suggest that antiepileptic drug generic substitution is associated with more health problems and high switchback rates, but these studies have insufficient detail on seizure control and blood levels. Several ongoing prospective randomized trials with rigorous pharmacokinetic methods aim to provide more data for decision-making. HubMed – drug

Influence of RNA structural elements on Ty1 retrotransposition.

Mob Genet Elements. 2013 Mar 1; 3(2): e25060
Purzycka KJ, Garfinkel DJ, Boeke JD, Le Grice SF

The long-terminal repeat (LTR)-retrotransposon Ty1 is a mobile genetic element that replicates through an RNA intermediate. Retroelement genomic transcripts contain internal structures fundamental to gene expression and propagation. In addition, long non-coding antisense RNAs overlap the 5′-terminal region of the genomic RNA and confer post-translational copy number control. Although LTR- retrotransposons are functionally related to retroviruses, little is known about the structural determinants required for genomic RNA packaging or reverse transcription. This commentary summarizes two recent papers that provide the first snapshot of genomic RNA structures from the retrotransposon Ty1 involved in transposition. We combined structural approaches with functional and genetic assays to determine if antisense RNAs anneal with the genomic RNA. Analysis of various steps in the Ty1 life cycle showed that a novel RNA pseudoknot contributes to retrotransposon function. Comparing different RNA states provides additional information about regions potentially involved in Ty1 RNA dimerization or packaging. HubMed – drug

In vitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-oped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive.

J Mater Chem B Mater Biol Med. 2013 Aug 7; 1(29): 3578-3587
Handa H, Brisbois EJ, Major TC, Refahiyat L, Amoako KA, Annich GM, Bartlett RH, Meyerhoff ME

Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion and activation that can be released from a NO donor species, such as diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) within a polymer coating. In this study, various Food and Drug Administration approved poly(lactic-co-glycolic acid) (PLGA) species were evaluated as additives to promote a prolonged NO release from DBHD/N2O2 within a plasticized poly(vinyl chloride) (PVC) matrix. When using an ester-capped PLGA additive with a slow hydrolysis time, the resulting coatings continuously release between 7-18×10(-10) mol cm(-2) min(-1) NO for 14 d at 37°C in PBS buffer. The corresponding pH changes within the polymer films were visualized using pH sensitive indicators and are shown to correlate with the extended NO release pattern. The optimal combined diazeniumdiolate/PLGA-doped NO release (NOrel) PVC coating was evaluated in vitro and its effect on the hemodynamics was also studied within a 4 h in vivo extracorporeal circulation (ECC) rabbit model of thrombogenicity. Four out of 7 control circuits clotted within 3 h, whereas all the NOrel coated circuits were patent after 4 h. Platelet counts on the NOrel ECC were preserved (79 ± 11% compared to 54 ± 6% controls). The NOrel coatings showed a significant decrease in the thrombus area as compared to the controls. Results suggest that by using ester-capped PLGAs as additives to a conventional plasticized PVC material containing a lipophilic diazeniumdiolates, the NO release can be prolonged for up to 2 weeks by controlling the pH within the organic phase of the coating. HubMed – drug

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