Response surface methodology for optimization of production of lovastatin by solid state fermentation

Lovastatin, an inhibitor of HMG-CoA reductase, was produced by solid state fermentation (SSF) using a strain of Aspergillus terreus UV 1718. Different solid substrates and various combinations thereof were evaluated for lovastatin production. Wheat bran supported the maximum production (1458 ± 46 µg g-1 DFM) of lovastatin. Response surface methodology (RSM) was applied to optimize the medium constituents. A 2(4) full-factorial central composite design (CCD) was chosen to explain the combined effects of the four medium constituents, viz. moisture content, particle size of the substrate, di-potassium hydrogen phosphate and trace ion solution concentration. Maximum lovastatin production of 2969 µg g-1 DFM was predicted by the quadratic model which was verified experimentally to be 3004 ± 25 µg g-1 DFM. Further RSM optimized medium supplemented with mycological, peptone supported highest yield of 3723.4±49 µg g-1 DFM. Yield of lovastatin increased 2.6 fold as with compared to un-optimized media.

Comparação entre lovastatina e o gemfibrozil no tratamento de hiperlipidemias primárias / Comparison between lovastatin and gemfibrozil in treatment of primary hyperlipidemias

Purpose - To compare the effects of lovastatin and gemfibrozil in patients with primary hyperlipidemias. Patients and Methods - Forty patients with cholesterolemia over 200 mgldl and triglyceridemia not higher than 350 mp/dl, excluded secondary causes, were selected. Twenty patients received lovastatin and 20 gemfibrozil. In order to establish the lipid profile, blood samples were taken after 2 months without medication, after 4 weeks of diet and placebo and after 6 and 12 weeks active treatment. Biochemic profile was determined before and after the treatment with active drug. Results - Thirty nine patients completed the study. Total and LDL-cholesterol were significantly reduced (p < 0.05) by both drugs but lovastatin had greater effect. Only gemfibrozil reduced triglycerides significantly. Neither drug had significant effects on HDL-cholesterol. The tolerance was satisfactory; only one patient (using gemfibrozil) needed to stop the treatment due to gastrointestinal side effects. The biochemic profïle did not present any significant alteration. Conclusion - Both drugs produced useful effects on the lipid profile. Lovastatin produced greater reductions of total and LDL-cholesterol, while gemfibrozil was more active reducing triglycerides. Neither drug changed significantly the HDL-cholesterol