- Family Elder
- Posts: 516
- Joined: Sat Feb 18, 2006 3:00 pm
- Location: suburb of Chicago, IL USA
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Drug combination therapies for central nervous system (CNS) demyelinating diseases including multiple sclerosis (MS) are gaining momentum over monotherapy. Over the past decade, both in vitro and in vivo studies established that statins (HMG-CoA reductase inhibitors) and rolipram (phosphodiesterase-4 inhibitor; blocks the degradation of intracellular cyclic AMP) can prevent the progression of MS in affected individuals via different mechanisms of action. In this study, we evaluated the effectiveness of lovastatin (LOV) and rolipram (RLP) in combination therapy to promote neurorepair in an inflammatory CNS demyelination model of MS, experimental autoimmune encephalomyelitis (EAE). Combination treatment with suboptimal doses of these drugs in an established case of EAE (clinical disease score > or = 2.0) significantly attenuated the infiltration of inflammatory cells and protected myelin sheath and axonal integrity in the CNS. It was accompanied with elevated level of cyclic AMP and activation of its associated protein kinase A. Interestingly, combination treatment with these drugs impeded neurodegeneration and promoted neurorepair in established EAE animals (clinical disease score > or = 3.5) as verified by quantitative real-time polymerase chain reaction, immunohistochemistry and electron microscopic analyses. These effects of combination therapy were minimal and/or absent with either drug alone in these settings. Together, these data suggest that combination therapy with LOV and RLP has the potential to provide neuroprotection and promote neurorepair in MS, and may have uses in other related CNS demyelinating diseases.
PMID: 18720408 [PubMed - in process]
These "suboptimal doses" would be interesting to hear what they actually were? i.e how sub-clinical were they in comparison to clinical doses?
The other interesting thing
Is there a Mouse EDSS?established case of EAE (clinical disease score > or = 2.0)
Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco (UFRPE), Recife, Brazil
Lovastatin producing by wild strain of Aspergillus terreus isolated from Brazil
Lovastatin is a drug in the statin class which acts as a natural inhibitor of 3-hydroxy-3-methylglutaryl, a coenzyme reductase reported as being a potential therapeutic agent for several diseases: Alzheimer's, multiple sclerosis, osteoporosis and due to its anti-cancer properties. Aspergillus terreus is known for producing a cholesterol reducing drug. This study sets out to evaluate the production of lovastatin by Brazilian wild strains of A. terreus isolated from a biological sample and natural sources. Carbon and nitrogen sources and the best physicochemical conditions using factorial design were also evaluated. The 37 fungal were grown to produce lovastatin by submerged fermentation. A. terreus URM5579 strain was the best lovastatin producer with a level of 13.96 mg/L. Soluble starch and soybean flour were found to be the most suitable substrates for producing lovastatin (41.23 mg/L) and biomass (6.1 mg/mL). The most favorable production conditions were found in run 16 with 60 g/L soluble starch, 15 g/L soybean flour, pH 7.5, 200 rpm and maintaining the solution at 32 °C for 7 days, which led to producing 100.86 mg/L of lovastatin and 17.68 mg/mL of biomass. Using natural strains and economically viable substrates helps to optimize the production of lovastatin and promote its use.