MedWorm: Lovastatin

Isoprenoid biosynthesis is required for miRNA function and affects membrane association of ARGONAUTE 1 in Arabidopsis [Plant Biology]

Proceedings of the National Academy of Sciences — Tue, 31 Jan 2012 05:00:00 +0100

Plant and metazoan microRNAs (miRNAs) guide ARGONAUTE (AGO) protein complexes to regulate expression of complementary RNAs via base pairing. In the plant Arabidopsis thaliana, the main miRNA effector is AGO1, but few other factors required for miRNA activity are known. Here, we isolate the genes defined by the previously described miRNA action deficient (mad) mutants, mad3 and mad4. Both genes encode enzymes involved in isoprenoid biosynthesis. MAD3 encodes 3-hydroxy-3-methylglutaryl CoA reductase (HMG1), which functions in the initial C5 building block biogenesis that precedes isoprenoid metabolism. HMG1 is a key regulatory enzyme that controls the amounts of isoprenoid end products. MAD4 encodes sterol C-8 isomerase (HYDRA1) that acts downstream in dedicated sterol biosynthesis. Using ye...

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Impact of CYP2D6 polymorphisms on the pharmacokinetics of lovastatin in Chinese subjects

European Journal of Clinical Pharmacology — Thu, 26 Jan 2012 16:45:55 +0100

Conclusion This study demonstrates that CYP2D6 polymorphisms appeared to influence the disposition of lovastatin lactone in these subjects. Content Type Journal ArticleCategory PharmacogeneticsPages 1-7DOI 10.1007/s00228-011-1202-5Authors Ophelia Qi Ping Yin, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongValiant Wah Lun Mak, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongMiao Hu, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongBenny Siu Pong Fok, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Ho...

Explication of interactions between HMGCR isoform 2 and various statins through In silico modeling and docking

Computers in Biology and Medicine — Sun, 22 Jan 2012 03:06:38 +0100

This study was designed to understand the mode of interactions of HMGCR isoform 2 with other statins. Hence, ligands such as Atorvastatin (DB01076), Lovastatin (DB00227), Fluvastatin (DB01095), Simvastatin (DB00641), Pravastatin (DB00175), Rosuvastatin (DB01098) and Cerivastatin (DB00439) were docked with enzymes HMGCR isoform 1 (pdb: 1DQ8) and modeled HMGCR isoform 2 (gi|196049380). Our homology modeling results were further processed to model the structure of human HMGCR isoform 2 and its accuracy was confirmed through RMS Z-scores (1.249). These interactions revealed that binding residues such as Arg515, Asp516, Tyr517 and Asn518 are found to be conserved in HMGCR isoform 2 with various statins. Our studies further concluded that Atorvastatin is most efficient inhibitor against both the...

Adverse events associated with individual statin treatments for cardiovascular disease: an indirect comparison meta-analysis

QJM — Mon, 16 Jan 2012 05:00:00 +0100

Discussion: Although statins are generally well tolerated, there are risks associated with almost all drugs. With few exceptions, statins appear to exert a similar risk across individual drugs. (Source: QJM)

Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin.

World Journal of Gastroenterology : WJG — Sat, 14 Jan 2012 05:00:00 +0100

CONCLUSION: The combinations of curcumin, EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts, these drugs also inhibited phosphorylated Erk1/2, c-Jun and COX-2 expression. PMID: 22253518 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

Uniform mesoporous carbon as a carrier for poorly water soluble drug and its cytotoxicity study.

European Journal of Pharmaceutics and Biopharmaceutics — Tue, 13 Dec 2011 05:00:00 +0100

In this study, uniform mesoporous carbon spheres (UMCS) with 3-D pore system and fibrous ordered mesoporous carbon (FOMC) with 2-dimensional hexagonal mesoporous structure were studied as drug carriers for oral drug delivery system. Lovastatin (LOV), which has low water solubility, was chosen as a model drug. Drug release rate and degree of drug loading of UMCS and FOMC were compared. The effects of different pore channel structures and pore sizes on LOV uptake and release were systematically investigated. Cytotoxicity of UMCS and FOMC on human colon carcinoma (Caco-2) cells were also studied. The results indicate that UMCS has a higher degree of drug loading (up to 36.26% drug weight/total weight) compared with FOMC. The dissolution rate of LOV from UMCS was found to be markedly increased...

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Adaptation to statins restricts human tumour growth in Nude mice

BMC Cancer — Tue, 22 Nov 2011 05:00:00 +0100

Conclusions: Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years. (Source: BMC Cancer)

Pravachol [pravastatin] and Mevacor [lovastatin] have the best muscle-related safety profile of statins marketed in the US

Reactions — Thu, 10 Nov 2011 08:03:53 +0100

(Source: Reactions)

Proteomics and bioinformatics analysis of lovastatin-induced differentiation in ARO cells.

Journal of Proteomics — Mon, 07 Nov 2011 05:00:00 +0100

Authors: Shui HA, Hsia CW, Chen HM, Chang TC, Wang CY Abstract Lovastatin (lova), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, can induce differentiation in cancer cells at low concentration, thus having potential to be used as an auxiliary agent in cancer therapy. However, biological networks associated with the differentiation effect of lova have not been elucidated. To investigate molecular mechanisms of lova, the present study was aimed at proteomics and bioinformatics analyses on anaplastic thyroid cancer cell line ARO differentiated with low concentration of lova. Thyroid differentiation was induced by treating ARO cells with 25μM of lova and confirmed by checking upregulation of some thyroid differentiation markers. Gel-based proteomics analysis was then per...

Prospective Analysis of Association Between Use of Statins or Other Lipid-Lowering Agents and Colorectal Cancer Risk

Annals of Epidemiology — Mon, 07 Nov 2011 05:00:00 +0100

Conclusions: There was a reduction in colorectal cancer risk associated with lovastatin and a nonsignificant association with longer duration of use. (Source: Annals of Epidemiology)

Prospective Analysis of Association Between Use of Statins or Other Lipid-Lowering Agents and Colorectal Cancer Risk.

Annals of Epidemiology — Thu, 03 Nov 2011 04:00:00 +0100

CONCLUSIONS: There was a reduction in colorectal cancer risk associated with lovastatin and a nonsignificant association with longer duration of use. PMID: 22056480 [PubMed - as supplied by publisher] (Source: Annals of Epidemiology)

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Long‐term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism

Nahrung / Food — Tue, 01 Nov 2011 04:00:00 +0100

Conclusion: Long‐term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti‐atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression. (Source: Nahrung / Food)

Lipid lowering drugs and gallstones: a therapeutic option?

Current Pharmaceutical Design — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Lioudaki E, Ganotakis ES, Mikhailidis DP Abstract Cholelithiasis is a common disease worldwide. The majority of gallstones can occur when the bile is supersaturated with cholesterol. Dyslipidaemia, obesity, insulin resistance are associated with an increased risk for cholesterol gallstone formation as well as with vascular risk. Statins and ezetimibe are used to treat dyslipidaemia and appear to have some effect on bile composition and cholesterol gallstone formation. Statin (e.g. pravastatin, simvastatin, fluvastatin and lovastatin) monotherapy or combined with ursodeoxycholic acid (UDCA) have shown reductions in bile cholesterol saturation, preventing gallstone formation and even dissolving pre-existing stones. However, this effect was not consistently reported in all st...

Preparation of lovastatin matrix sustained-release pellets by extrusion-spheronization combined with microcrystal dispersion technique.

Archives of Pharmacal Research — Tue, 01 Nov 2011 04:00:00 +0100

In this study, a microcrystal dispersion (MCD) technique was used in the preparation of LVA to increase its dissolution rate and then combining with an extrusion-spheronization method, microcrystalline cellulose (MCC) matrix sustained-release pellets containing LVA-MCD were developed and characterized in vitro. Photomicrographs indicated that LVA-MCD existed as fine crystals, of which the mean particle size was reduced from 65.75 μm to 3.97 μm and the dried LVA-MCD powders released completely within 2 hours. SEM results during the release process showed that pellets possessed a matrix structure and after the dissolution test, this matrix structure became loose and porous. The release of LVA was fast and complete, and accumulated release by the optimal formulation was: 0.5 h (20.23 ± 3.4...

Do statins cut breast cancer recurrence?

NHS News Feed — Mon, 31 Oct 2011 10:31:00 +0100

Conclusion In this cohort study, use of a lipophilic statin (including simvastatin, the most commonly prescribed of the statins) was associated with a reduced risk of recurrent breast cancer in women with invasive breast cancer. The researchers also investigated the association between the exclusive use of simvastatin and the risk of recurrent breast cancer, and found that use of simvastatin reduced the risk of recurrent breast cancer compared to no statin treatment or treatment with a hydrophilic statin. Use of a hydrophilic (water-soluble) statin, including atorvastatin, pravastatin or rosuvastatin, was not found to be associated with reduced risk, though the strength of this result is limited by the small proportion of statin users (only 6%) who used this type of statin. The trial also...

Nature’s Cholesterol-Lowering Drug: Isolation and Structure Elucidation of Lovastatin from Red Yeast Rice-Containing Dietary Supplements

Journal of Chemical Education — Fri, 28 Oct 2011 13:32:34 +0100

Journal of Chemical EducationDOI: 10.1021/ed1004195 (Source: Journal of Chemical Education)

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Modifiers of Symptomatic Embolic Risk in Infective Endocarditis

Mayo Clinic Proceedings — Thu, 27 Oct 2011 04:00:00 +0100

CONCLUSION: The rate of symptomatic emboli associated with IE was reduced in patients who received continuous daily statin therapy before onset of IE. Despite fewer embolic events observed in patients who received antiplatelet agents, a significant association was not found after adjusting for propensity factors. A continued evaluation of these drugs and their potential impact on subsequent embolism among IE patients is warranted. (Source: Mayo Clinic Proceedings)

Changes in Cholesterol Homeostasis Modify the Response of F1B hamsters to Dietary Very Long Chain n-3 and n-6 Polyunsaturated Fatty Acids

Lipids in Health and Disease — Fri, 21 Oct 2011 04:00:00 +0100

Background: The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Results: Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) ...

Statin effects on regulatory and proinflammatory factors in chronic idiopathic urticaria.

Clinical and Developmental Immunology — Fri, 14 Oct 2011 19:32:47 +0100

Authors: Azor MH, Dos Santos JC, Futata EA, de Brito CA, Maruta CW, Rivitti EA, da Silva Duarte AJ, Sato MN Abstract Immunological dysfunction has been described to occur in chronic idiopathic urticaria (CIU), most notably in association with an inflammatory process. Some pharmacological agents as statins - drugs used in hypercholesterolaemia - display a broad effect on the immune response and thus should be tested in vitro in CIU. Our main objectives were to evaluate the effects of statins on the innate and adaptive immune response in CIU. Simvastatin or lovastatin have markedly inhibited the peripheral blood mononuclear cells (PBMC) proliferative response induced by T and B cell mitogens, superantigen or recall antigen. Simvastatin arrested phytohaemaglutinin (PHA)-induced T cell...

A novel bisphosphonate inhibitor of squalene synthase combined with a statin or a nitrogenous bisphosphonate in vitro [Research Articles]

The Journal of Lipid Research — Fri, 14 Oct 2011 04:00:00 +0100

Statins and nitrogenous bisphosphonates (NBP) inhibit 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR) and farnesyl diphosphate synthase (FDPS), respectively, leading to depletion of farnesyl diphosphate (FPP) and disruption of protein prenylation. Squalene synthase (SQS) utilizes FPP in the first committed step from the mevalonate pathway toward cholesterol biosynthesis. Herein, we have identified novel bisphosphonates as potent and specific inhibitors of SQS, including the tetrasodium salt of 9-biphenyl-4,8-dimethyl-nona-3,7-dienyl-1,1-bisphosphonic acid (compound 5). Compound 5 reduced cholesterol biosynthesis and lead to a substantial intracellular accumulation of FPP without reducing cell viability in HepG2 cells. At high concentrations, lovastatin and zoledronate impaired prot...

Cost-effectiveness of the use of low- and high-potency statins in people at low cardiovascular risk.

cmaj — Tue, 11 Oct 2011 04:00:00 +0100

Authors: Conly J, Clement F, Tonelli M, Hemmelgarn B, Klarenbach S, Lloyd A, McAlister FA, Husereau D, Wiebe N, Au F, Manns B Abstract BACKGROUND:Although statins have been shown to reduce the risk of cardiovascular events in patients at low cardiovascular risk, their absolute benefit is small in the short term, which may adversely affect cost-effectiveness. We sought to determine the long-term cost-effectiveness (beyond the duration of clinical trials) of low- and high-potency statins in patients at low cardiovascular risk and to estimate the impact on Canada's publicly funded health care system. METHODS:Using Markov modelling, we performed a cost-utility analysis in which we compared low-potency statins (fluvastatin, lovastatin, prava statin and simvastatin) and high-potency stat...

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Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

Gut — Fri, 30 Sep 2011 04:00:00 +0100

Conclusions Statins act as DNMT inhibitors, demethylating the BMP2 promoter, activating BMP signalling, inducing differentiation of CRC cells, and reducing ‘stemness’. This study indicates that statins may be able to be used as differentiating agents in combined or adjuvant therapy in CRC with the CpG island methylator phenotype. (Source: Gut)

Learning Disabilities In Patients With Neurofibromatosis May Be Treated With Common Cholesterol Drug

Health News from Medical News Today — Thu, 29 Sep 2011 08:00:00 +0100

Researchers at Children's National Medical Center have found that a cholesterol-lowering statin drug appears to be safe in children with neurofibromatosis type 1 (NF1) and may improve learning disabilities, including verbal and nonverbal memory. This is the first time that the drug lovastatin has been studied in children with NF1. The study, led by Maria T. Acosta, MD, a pediatric neurologist and researcher at Children's National and clinical director and cognitive director of the Gilbert Family Neurofibromatosis Institute, appears in the October 2011 issue of /iPediatric Neurology... (Source: Health News from Medical News Today)

LOVASTATIN (Lovastatin) Tablet [REMEDYREPACK INC. ]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 23 Sep 2011 05:00:00 +0100

Updated Date: Sep 23, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

The doubtful association between blood lipid changes and progression of atherosclerosis

International Journal of Cardiology — Wed, 21 Sep 2011 04:00:00 +0100

Recently Tenenbaum et al. reported that long-term changes in serum cholesterol did not correlate with the progression of coronary calcium measured by computerized tomography . Their finding shows that the benefit of various cholesterol-lowering treatments obtained in many angiographic trials must be caused by other and unknown factors. The authors argued that one of the reasons to the lack of exposure–response may be that calcific plaques are resistant to undergoing changes in size in response to systemic anti-atherosclerotic therapy. However, other studies using different techniques and other kinds of outcome have also shown lack of exposure–response. In a previous review of the angiographic cholesterol-lowering trials I identified sixteen trials in which the authors had calculated ex...

Preparation and Characterization of a Lovastatin-Loaded Protein-Free Nanostructured Lipid Carrier Resembling High-Density Lipoprotein and Evaluation of its Targeting to Foam Cells.

AAPS PharmSciTech — Sat, 17 Sep 2011 04:00:00 +0100

This study was designed to investigate whether a non-protein nanostructured lipid carrier (NLC) resembling high-density lipoprotein (HDL) could deliver a hydrophobic anti-atherogenic drug, lovastatin, to foam cells. Lovastatin-loaded NLC (LT-NLC) was prepared by a nanoprecipitation/solvent diffusion method. The LT-NLC-apoprotein (LT-NLC-apo) was prepared by incubating LT-NLC with native HDL. The physicochemical parameters of LT-NLC were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and crystallization behavior. Targeting behavior and mechanism were demonstrated by the incubation of LT-NLC-apo with a RAW 264.7 macrophage-derived foam cell model in the presence or absence of very-low-density lipoprotein (VLDL) and lipase. The results showed that ...

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Simultaneous determination of simvastatin, lovastatin and niacin in human plasma by LC-MS/MS and its application to a human pharmacokinetic study.

Biomedical Chromatography : BMC — Wed, 14 Sep 2011 04:00:00 +0100

Authors: Rao Pilli N, Mullangi R, Kuamr Inamadugu J, Kumari Nallapati I, N Seshagiri Rao JV Abstract A simple, sensitive and specific LC-MS/MS method for simultaneous determination of simvastatin (SV), lovastatin (LV) and niacin (NIA) in human plasma was developed and validated on API-4000 in positive ion mode. Nevirapine was used as internal standard (IS). The assay procedure involved a simple one-step liquid-liquid extraction of SV, LV, NIA and the IS from plasma into ethyl acetate. Separation of SV, LV, NIA and the IS was achieved on an Alltima C(18) column with a mobile phase consisting of 5 m m ammonium acetate (pH 4.5) and acetonitrile (20:80, v/v) pumped at a flow rate of 1 mL/min. Nominal retention times obtained for SV, LV, NIA and IS were 2.12, 1.67, 0.50 and 0.65 m...

Lovastatin as Treatment for Neurocognitive Deficits in Neurofibromatosis Type 1: Phase I Study

Pediatric Neurology — Tue, 13 Sep 2011 03:39:28 +0100

We report on a phase I study examining the safety and tolerability of lovastatin in children with neurofibromatosis type 1. Twenty-four children with neurofibromatosis type 1 underwent a dose-escalation protocol for 3 months to identify the maximum tolerated dose and potential toxicity. Minimal side effects were evident, and no child experienced dose-limiting toxicity. Cognitive evaluations were completed before and after treatment, and the results suggested improvement in areas of verbal and nonverbal memory. Additional analyses, using reliable change indices, indicated improvements exceeding those of test-retest or practice effects in some participants. These observations may be analogous to the improvements observed in a neurofibromatosis type 1 murine model treated with lovastatin, alt...

Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: a role of combined treatment versus monotherapy

Apoptosis — Sat, 10 Sep 2011 15:47:04 +0100

Abstract Treatment of melanoma cells by sodium arsenite or statins (simvastatin and lovastatin) dramatically modified activities of the main cell signaling pathways resulting in the induction of heme oxygenase-1 (HO-1) and in a downregulation of cyclooxygenase-2 (COX-2) protein levels. Through heme degradation and the production of carbon monoxide and biliverdin, HO-1 plays a protective role in different scenario of oxidative stress followed by mitochondrial apoptosis. Both sodium arsenite and statins could be efficient inducers of apoptosis in some melanoma cell lines, but often exhibited only modest proapoptotic activity in others, due to numerous protective mechanisms. We demonstrated in the present study that treatment by sodium arsenite or statins with an additional i...

Inhibition of neuronal cholesterol biosynthesis with lovastatin leads to impaired synaptic vesicle release even in the presence of lipoproteins or geranylgeraniol

Journal of Neurochemistry — Wed, 07 Sep 2011 04:00:00 +0100

AbstractCholesterol is highly enriched in the brain, and plays a key role in synapse formation and function. The brain does not derive cholesterol from the circulation; instead, the majority of cholesterol is made in glia and secreted in form of lipoproteins. Neurons can synthesize cholesterol, but the extent of neuronal cholesterol biosynthesis in the adult brain is unknown. Cholesterol biosynthesis inhibitors of the statin family are widely used to lower circulating cholesterol and cardiovascular risk. Lipophilic statins can cross the blood brain barrier and inhibit brain cholesterol biosynthesis with possible consequences for synaptic cholesterol homeostasis. We have investigated the effects of lovastatin on synapse maturation and synaptic vesicle release. Treatment of primary hippocamp...

Statins inhibit iNOS‐mediated microbicidal potential of activated monocyte‐derived dendritic cells by an IFN‐β‐dependent mechanism

European Journal of Immunology — Mon, 22 Aug 2011 23:00:00 +0100

AbstractStatins are prescribed to 25‐million people worldwide for treating hypercholesterolemia and reducing the risk of cardiovascular diseases. However the side effects of statins on immunity, and particularly on DC immunobiology, have not been analyzed in‐depth. Here we have investigated the impact of lovastatin treatment during monocyte differentiation into DCs on the responsiveness of the resulting monocyte‐derived DCs (moDCs) to TLR‐mediated activation. Lovastatin positively regulated TLR4 signaling in LPS‐stimulated moDCs, leading to a strong activation of p38 MAP‐kinase paralleled by increased proinflammatory cytokine and IFN‐ production. In contrast, lovastatin promoted a negative regulation of IFN‐β‐mediated autocrine signaling through the IFNαβ receptor, par...

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Statins inhibit iNOS-mediated microbicidal potential of activated monocyte-derived dendritic cells by an IFN-β-dependent mechanism.

European Journal of Immunology — Mon, 22 Aug 2011 23:00:00 +0100

Authors: Domínguez PM, López-Bravo M, Kalinke U, Ardavín C Abstract Statins are prescribed to 25-million people worldwide for treating hypercholesterolemia and reducing the risk of cardiovascular diseases. However the side effects of statins on immunity, and particularly on DC immunobiology, have not been analyzed in-depth. Here we have investigated the impact of lovastatin treatment during monocyte differentiation into DCs on the responsiveness of the resulting monocyte-derived DCs (moDCs) to TLR-mediated activation. Lovastatin positively regulated TLR4 signaling in LPS-stimulated moDCs, leading to a strong activation of p38 MAP-kinase paralleled by increased proinflammatory cytokine and IFN- production. In contrast, lovastatin promoted a negative regulation of IFN-β-mediated ...

Fluvastatin modulates renal water reabsorption in vivo through increased AQP2 availability at the apical plasma membrane of collecting duct cells.

Pflugers Archiv : European Journal of Physiology — Fri, 19 Aug 2011 23:00:00 +0100

In conclusion, these results strongly suggest that fluvastatin, or other drugs of the statin family, may prove useful in the therapy of XNDI. PMID: 21858457 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)

Therapeutics for Childhood Neurofibromatosis Type 1 and Type 2

Current Treatment Options in Neurology — Thu, 18 Aug 2011 06:02:54 +0100

Opinion statement Neurofibromatosis type 1 (NF1) and type 2 (NF2) are genetically and medically distinct neurocutaneous disorders that are both associated with tumors affecting the central and peripheral nervous systems. NF1 has a frequency of 1 in 3,000, compared with 1 in 30,000 for NF2. Careful surveillance is important for both conditions, to allow early identification and treatment of complications. The most common and important problems in NF1 are cognitive impairment, optic pathway gliomas, plexiform neurofibromas, and orthopaedic issues. Early intervention and tailored educational programs are indicated for learning difficulties. Attention deficit hyperactivity disorder may be amenable to treatment with stimulant medication. A clinical trial is under way to evaluate...

Statin effects on regulatory and proinflammatory factors in chronic idiopathic urticaria

Clinical and Experimental Immunology — Tue, 16 Aug 2011 15:03:20 +0100

AbstractImmunological dysfunction has been described to occur in chronic idiopathic urticaria (CIU), most notably in association with an inflammatory process. Some pharmacological agents as statins—drugs used in hypercholesterolemia — display a broad effect on the immune response and thus should be tested in vitro against CIU. Our main objectives were to evaluate the effects of statins on the innate and adaptive immune response in CIU. Simvastatin or lovastatin have markedly inhibited the peripheral blood mononuclear cells (PBMC) proliferative response induced by T and B cell mitogens, superantigen or recall antigen. Simvastatin arrested phytohemaglutinin (PHA) induced T‐cells at G0/G1 phase, inhibiting Th1, Th2, IL‐10 and IL‐17A cytokine secretion in both patients and healthy co...

Association of lower total bilirubin level with statin usage: The United States National Health and Nutrition Examination Survey 1999–2008

Atherosclerosis — Tue, 16 Aug 2011 04:00:00 +0100

Abstract: Objective: A low circulating level of bilirubin is associated with increased cardiovascular risk. As statins can stimulate heme oxygenase-1 (HO-1), which increases bilirubin production, we investigated whether statins in routine use increase total bilirubin levels in subjects at high cardiovascular risk.Methods: Data from 3290 subjects with self-reported history of hypercholesterolemia, diabetes, or cardiovascular diseases in the United States National Health and Nutrition Examination Survey (NHANES) 1999–2008 were analyzed.Results: Subjects taking statins (n=1156) had lower total bilirubin levels than those not taking any lipid-lowering medication (n=2134) after adjusting for age, sex, race/ethnicity, and survey period (adjusted mean=0.699 vs 0.729mg/dl respectively, P=0.001)....

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Antihyperlipidemic activity of Cassia auriculata flowers in triton WR 1339 induced hyperlipidemic rats.

Experimental and Toxicologic Pathology — Mon, 15 Aug 2011 23:00:00 +0100

Authors: Vijayaraj P, Muthukumar K, Sabarirajan J, Nachiappan V Abstract The flower extract of Cassia auriculata, herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of C. auriculata flower on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intravenous (iv) injection of Triton WR 1339 (300mg/kg b.w.) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of C. auriculata flowers (Et-CAF) (150, 300, ...

Characterization of Lovastatin biosynthetic cluster proteins in Aspergillus terreus strain ATCC 20542

The Aspergillus Website - articles — Fri, 05 Aug 2011 12:58:29 +0100

Subazini TK, Kumar GR (Source: The Aspergillus Website - articles)

Pfizer Wants Atorvastatin Available Over the CounterPfizer Wants Atorvastatin Available Over the Counter

Medscape Today Headlines — Thu, 04 Aug 2011 19:14:17 +0100

The switch from an $11-billion/year drug juggernaut to an OTC medication won't be easy for Pfizer, as the FDA has turned Merck away multiple times when it made similar pitches to have lovastatin available to consumers without a prescription. Heartwire (Source: Medscape Today Headlines)

Pfizer wants atorvastatin available over the counter: Wall Street Journal

theHeart.org — Thu, 04 Aug 2011 18:00:34 +0100

Specific considerations on the prescription and therapeutic interchange of statins.

Farmacia Hospitalaria — Wed, 03 Aug 2011 23:00:00 +0100

CONCLUSION: The pharmacokinetics is important when choosing the best statin and could be a limitation in the use of interchange therapeutic programmes when other drugs are present. PMID: 21820929 [PubMed - as supplied by publisher] (Source: Farmacia Hospitalaria)

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Antioxidant effect of red mould rice in hypercholesterolemic Wistar male rats

Cell Biochemistry and Function — Sun, 31 Jul 2011 23:00:00 +0100

The effect of Monascus purpureus red mould rice (RMR) on modulation of lipid metabolism and oxidative stress was studied in hypercholesterolemic rats. Cholesterol feeding for 14 weeks caused a significant increase in the lipid peroxides and total thiols and antioxidant enzymes, viz. glutathione peroxidase (GPx), glutathione reductase (GRd), superoxide dismutase (SOD) and catalase (CAT) in serum and liver in comparison to the control group. However, supplementation of RMR to hypercholesterolemic rats at 8, 12 and 16% significantly increased the GRd, GPx, SOD and CAT activities in serum and liver tissues. Furthermore, RMR feeding significantly decreased total thiols and lipid peroxides and also increased other antioxidant molecules such as glutathione and ascorbic acid in high‐cholestero...

Diallyl disulphide and lovastatin: effects on energy and protein utilisation in, as well as methane emission from, sheep.

Archives of Animal Nutrition — Sun, 31 Jul 2011 23:00:00 +0100

In conclusion, the study demonstrated a certain potential of DADS to improve fibre digestion and body energy retention and to limit CH4 formation in relation to digestible fibre intake, while lovastatin remained ineffective. PMID: 21888032 [PubMed - in process] (Source: Archives of Animal Nutrition)

Danazol/lovastatin interaction: Rhabdomyolysis in an elderly patient: case report

Reactions — Sun, 24 Jul 2011 19:59:43 +0100

(Source: Reactions)

Characterization of Lovastatin biosynthetic cluster proteins in Aspergillus terreus strain ATCC 20542.

Bioinformation — Fri, 22 Jul 2011 03:13:31 +0100

Authors: Subazini TK, Kumar GR Aspergillus terreus is a filamentous ascomycota, which is prominent for its production of lovastatin, an antihypercholesterolemic drug. The commercial importance of lovastatin with annual sales of billions of dollars made us to focus on lovastatin biosynthetic cluster proteins. The analysis of these lovastatin biosynthetic cluster proteins with different perspectives such as physicochemical property, structure based analysis and functional studies were done to find out the role and function of every protein involved in the lovastatin biosynthesis pathway. Several computational tools are used to predict the physicochemical properties, secondary structural features, topology, patterns, domains and cellular location. There are 8 unidentified proteins in lova...

The Cytostatic Effects of Lovastatin on ACC-MESO-1 Cells

Journal of Surgical Research — Mon, 18 Jul 2011 04:00:00 +0100

Conclusions: These results suggest that it may be possible to utilize statins, or other pharmacological agents that are known to induce mTOR-independent autophagy, as an adjunct to standard treatments in malignant mesothelioma. (Source: Journal of Surgical Research)

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Sensitivity to Lovastatin of Saccharomyces cerevisiae Strains Deleted for Pleiotropic Drug Resistance (PDR) Genes

Journal of Molecular Microbiology and Biotechnology — Mon, 11 Jul 2011 23:00:00 +0100

J Mol Microbiol Biotechnol 2011;20:191–195 (DOI:10.1159/000329068) (Source: Journal of Molecular Microbiology and Biotechnology)

Synergistic inhibitory effect of apomine and lovastatin on osteosarcoma cell growth

Cancer — Mon, 11 Jul 2011 23:00:00 +0100

CONCLUSIONS:The results from this study revealed that combination therapy with apomine and lovastatin may be a novel treatment strategy for osteosarcoma. Cancer 2011;. © 2011 American Cancer Society. (Source: Cancer)

Induction of a High-Yield Lovastatin Mutant of Aspergillus terreus by (12)C (6+) Heavy-Ion Beam Irradiation and the Influence of Culture Conditions on Lovastatin Production Under Submerged Fermentation.

Applied Biochemistry and Biotechnology — Mon, 27 Jun 2011 23:00:00 +0100

In this study, the heavy-ion beams generated by the Heavy-Ion Research Facility in Lanzhou were used to mutagenize Aspergillus terreus CA99 for screening high-yield lovastatin strains. Furthermore, the main growth conditions as well as the influences of carbon and nitrogen sources on the growth and the lovastatin production of the mutant and the original strains were investigated comparatively. The spores of A. terreus CA99 were irradiated by 15, 20, 25, and 30 Gy of 80 MeV/u (12)C(6+) heavy-ion beams. Based on the lovastatin contents in the fermentation broth, a strain designated as A. terreus Z15-7 has been selected from the clone irradiated by the heavy-ion beam. When compared with the original strain, the content of lovastatin in the fermentation broth of A. terreus Z15-7 increased 4...

Unexplained Anemia and Neutropenia

Gastroenterology — Sun, 26 Jun 2011 23:00:00 +0100

Question: An 81-year-old man presented with fatigue and exercise intolerance. The patient's medical history was unremarkable except for mild hypertension, hyperlipidemia, and an episode 30 years earlier when the patient presented with melena related to antral ulcers, requiring numerous blood transfusions and leading to antrectomy with gastrojejunostomy (Billroth II). He has had no further episodes of overt gastrointestinal bleeding. He reported taking a daily baby aspirin, metoprolol, lovastatin, and multivitamins. He also noted intermittent intake of oral zinc supplements, which were started prophylactically by his primary care physician to avoid zinc deficiency after his gastrojejunostomy. The physical examination demonstrated normal vital signs, mild pallor, and a nontender abdomen; rec...

Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma

Annals of Hematology — Wed, 22 Jun 2011 16:03:50 +0100

Abstract The treatment of patients with multiple myeloma usually includes many drugs including thalidomide, lenalidomide and bortezomib. Lovastatin and other inhibitors of HMG-CoA reductase demonstrated to exhibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines. We treated 91 patients with relapsed or refractory multiple myeloma with thalidomide, dexamethasone and lovastatin (TDL group, 49 patients) or thalidomide and dexamethasone (TD group, 42 patients). A clinical response defined of at least 50% reduction of monoclonal band has been observed in 32% of TD patients and 44% of TDL patients. Prolongation of overall survival and progression-free survival in the TDL group as compared with the TD group has been documented...

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LOVASTATIN (Lovastatin) Tablet [REMEDYREPACK INC. ]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 10 Jun 2011 05:00:00 +0100

Updated Date: Jun 10, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Lovastatin Causes Diminished PSA Secretion by Inhibiting AR Expression and Function in LNCaP Prostate Cancer Cells

Urology — Tue, 31 May 2011 21:15:13 +0100

Conclusions: Our data suggest that the regular use of statins may have beneficial effects in statin users by preventing prostate cancer growth through inhibition of androgen activation and expression, resulting in diminished PSA levels. (Source: Urology)

SR-PSOX at sites predisposed to atherosclerotic lesion formation mediates monocyte-endothelial cell adhesion

Atherosclerosis — Wed, 25 May 2011 23:00:00 +0100

Conclusions: : We suggest that SR-PSOX/CXCL16 may promote the adhesion of monocytes to the endothelium during early atherogenesis and that accumulating cytokines enhance SR-PSOX/CXCL16-mediated adhesion by upregulating SR-PSOX/CXCL16 expression. Manipulation of SR-PSOX/CXCL16 expression with anti-inflammatory agents may be of therapeutic value. (Source: Atherosclerosis)

Function of MRP1 is not dependent on cholesterol or cholesterol-stabilized lipid rafts

BJ Cell — Mon, 23 May 2011 23:00:00 +0100

In conclusion, MRP1/Mrp1 activity is not correlated with the level of free cholesterol or with localization in cholesterol-dependent lipid rafts. (Source: BJ Cell)

Induced pluripotent stem cell models from X‐linked adrenoleukodystrophy patients

Annals of Neurology — Thu, 19 May 2011 23:00:00 +0100

AbstractObjective:Because of a lack of an appropriate animal model system and the inaccessibility of human oligodendrocytes in vivo, X‐linked adrenoleukodystrophy (X‐ALD)‐induced pluripotent stem cells (iPSCs) would provide a unique cellular model for studying etiopathophysiology and development of therapeutics for X‐ALD.Methods:We generated and characterized iPSCs of the two major types of X‐ALD: CCALD and AMN, and differentiated them into oligodendrocytes and neurons. We evaluated disease‐relevant phenotypes by pharmacological and genetic approaches.Results:We established iPSCs from the patients with childhood cerebral ALD (CCALD) and adrenomyeloneuropathy (AMN), the two major types of X‐ALD. Both CCALD‐ and AMN‐iPSCs normally differentiated into oligodendrocytes, the c...

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Juvenile toxicity assessment of open‐acid lovastatin in rats

Birth Defects Research Part B: Developmental and Reproductive Toxicology — Tue, 17 May 2011 23:00:00 +0100

CONCLUSION: Based on these results, the no‐effect level for general and neurobehavioral toxicity in neonatal rats was ≥10 mg/kg/day for open‐acid lovastatin. Birth Defects Res (Part B) XX:1–9, 2011. © 2011 Wiley‐Liss, Inc. (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)

Is There a Treatment Advantage When Paclitaxel and Lovastatin Are Combined to Dose Anaplastic Thyroid Carcinoma Cell Lines?

Thyroid — Fri, 13 May 2011 22:24:45 +0100

Thyroid , Vol. 0, No. 0. (Source: Thyroid)

Red Mold Rice Mitigates Oral Carcinogenesis in 7,12-Dimethyl-1,2-Benz[a]anthracene-Induced Oral Carcinogenesis in Hamster

Journal of Oncology — Thu, 05 May 2011 14:35:30 +0100

In this study, we examined the anti-tumor effect of red mold rice on 7,12-dimethyl-1,2-benz[a]anthracene (DMBA)-induced oral tumor in hamster. The ethanol extract of red mold rice (RMRE) treatment significantly decreases the levels of DMBA-induced reactive oxygen species, nitro oxide and prostaglandin E2 than those of the lovastatin-treated group (P < .001). Moreover, RMRE decreases the formation of oral tumor induced by DMBA. Monacolin K, monascin, ankaflavin or other red mold rice metabolites had been reported to decrease inflammation and oxidative stress and exerted anti-tumor effects. Therefore, we evaluated the anti-inflammation and anti-oxidative stress effects of monacolin K, monascin, ankaflavin and citrinin in lipopolysaccharide-treated RAW264.7 cells. We found that RMRE redu...

Synthesis and antihyperlipidemic efficiency of berberine-based HMG-CoA reductase inhibitor

Medicinal Chemistry Research — Wed, 04 May 2011 14:54:48 +0100

Abstract From more than 100 simulation-designed compounds, 8-alkyl-berberine derivatives with a long aliphatic chain (n = 10–20) were chosen and successfully synthesized to evaluate their antihyperlipidemic activity. With elongating the aliphatic chain, the inhibition of derivatives to HMG-CoA reductase (HMGR) and the LD50 increased gradually. Especially, 8-hexadecyl-berberine (4D) with 8.0 μmol/l significantly inhibited HMGR, even higher than lovastatin. Then, the inhibition gradually decreased with the aliphatic chain further elongating. Animal experiments showed that all tested derivatives could improve blood lipid level to different degree. Similarly, compound 4D showed the best lipid-reducing efficiency especially for TC and LDL-c level which were near ...

Efficacy of Ezetimibe/Statins and Statin Monotherapy and Factors Associated with Treatment Response: Pooled Analysis of >21,000 Subjects from 27 Trials

Journal of Clinical Lipidology — Sat, 30 Apr 2011 23:00:00 +0100

Synopsis: Use of a large pooled database from multiple clinical trials provides additional power to assess the efficacy of lipid-altering therapy. Purpose: To evaluate the lipid-altering efficacy of ezetimibe co-administered with statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin) and statin monotherapy. Identify factors related to treatment response. (Source: Journal of Clinical Lipidology)

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Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair‐deficient chicken DT40 cell lines

Environmental and Molecular Mutagenesis — Tue, 26 Apr 2011 23:00:00 +0100

AbstractIncluded among the quantitative high throughput screens (qHTS) conducted in support of the US Tox21 program are those being evaluated for the detection of genotoxic compounds. One such screen is based on the induction of increased cytotoxicity in seven isogenic chicken DT40 cell lines deficient in DNA repair pathways compared to the parental DNA repair‐proficient cell line. To characterize the utility of this approach for detecting genotoxic compounds and identifying the type(s) of DNA damage induced, we evaluated nine of 42 compounds identified as positive for differential cytotoxicity in qHTS (actinomycin D, adriamycin, alachlor, benzotrichloride, diglycidyl resorcinol ether, lovastatin, melphalan, trans‐1,4‐dichloro‐2‐butene, tris(2,3‐epoxypropyl)isocyanurate) and on...

Diltiazem/lovastatin interaction: Rhabdomyolysis in an elderly patient: case report

Reactions — Sun, 24 Apr 2011 16:50:04 +0100

(Source: Reactions)

Structure modeling and inhibitor prediction ofNADP oxidoreductase enzyme from Methanobrevibacter smithii.

Bioinformation — Mon, 11 Apr 2011 12:45:16 +0100

Authors: Sharma A, Chaudhary PP, Sirohi SK, Saxena J The F420-dependent NADP oxidoreductase enzyme from Methanobrevibacter smithii catalyzes the important electron transfer step during methanogenesis. Therefore, it may act as potential target for blocking the process of methane formation. Its protein sequence is available in GenBank (accession number: ABQ86254.1) however no report has been found about its 3D protein structure. In this work, we first time claim 3D model structure of F420-dependent NADP oxidoreductase enzyme from Methanobrevibacter smithii by comparative homology modeling method. Swiss model and ESyPred3d (via Modeller 6v2) software's were generated the 3D model by detecting 1JAX (A) as template along with sequence identities of 34.272% and 35.40%. Furthermore, PROCHECK ...

LOVASTATIN (Lovastatin) Tablet [AvPAK]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Mon, 11 Apr 2011 05:00:00 +0100

Updated Date: Apr 11, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

The 2′,4′,6′-Trihydroxyacetophenone Isolated from Myrcia multiflora Has Antiobesity and Mixed Hypolipidemic Effects with the Reduction of Lipid Intestinal Absorption

Planta Medica — Tue, 05 Apr 2011 23:00:00 +0100

This study evaluated the hypolipidemic and antiobesity effects of phloroacetophenone (2′,4′,6′-trihydroxyacetophenone, THA) isolated from Myrcia multiflora and their relationship with triglyceride (TG) intestinal absorption and pancreatic lipase activity inhibition. The hypolipidemic effect of THA was evaluated by acute (Triton WR-1339 treatment) and chronic assay (high-fat diet treatment), the antiobesity effect was evaluated by chronic assay (high-fat diet treatment), while the inhibition of enzymatic activity of pancreatic lipase was measured in the intestinal tissue of mice treated with high olive oil concentration. In the acute assay, THA caused greater total cholesterol (37 %) and triglyceride (46 %) serum level reduction than lovastatin (32 and 1 %), a HMG‐Co...

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Highly efficient release of lovastatin from poly(lactic‐co‐glycolic acid) nanoparticles enhances bone repair in rats

Journal of Orthopaedic Research — Thu, 31 Mar 2011 23:00:00 +0100

This study optimized the emulsion (o/w) technique in the fabrication process for PLGA nanoparticles, thereby producing the first recorded case of a high release rate (97%) of lovastatin. We also calculated the calibration curve of lovastatin using a UV spectrometer. The results demonstrated that the ALPase activity in human osteoblasts could be significantly stimulated by lovastatin carried in PLGA nanoparticles, but was prominently decreased by free lovastatin with the concentration higher than 4 µg/ml. Animal studies showed that the amount of lovastatin contained in 1 mg PLGA was the optimum dosage. These results suggest the new lovastatin‐releasing PLGA delivery device exhibits potential for clinical treatment of bony defects. © 2011 Orthopaedic Research Society Published by W...

The effect of dyslipidemic drugs on mortality: a meta-analysis

NeLM - Disease Focused Reviews — Sun, 27 Mar 2011 23:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review evaluated the effect of lipid-lowering drugs on coronary artery disease and cardiovascular disease mortalities, and all-cause mortality. The authors concluded that reductions of 15 to 25% in the relative odds of developing these outcomes can be achieved. This was largely a well-conducted review, but the absence of trial quality assessment represents a threat to the reliability of findings. [The included drugs were cholestyramine, clofibrate, fluvastatin, gemfibrozil, lovastatin, pravastatin and simvastatin.] CRD Commentary: This review addressed a clear research question. This was supported by inclusion criteria, which were detailed for study design and outcomes, and broad for the intervention of interest. ...

Simvastatin Targets CD44 to Inhibit Breast Cancer Metastasis [Signal Transduction]

Journal of Biological Chemistry — Fri, 25 Mar 2011 00:00:00 +0100

Substantial data from clinical trials and epidemiological studies show promising results for use of statins in many cancers, including mammary carcinoma. Breast tumor primarily metastasizes to bone to form osteolytic lesions, causing severe pain and pathological fracture. Here, we report that simvastatin acts as an inhibitor of osteolysis in a mouse model of breast cancer skeletal metastasis of human mammary cancer cell MDA-MB-231, which expresses the mutant p53R280K. Simvastatin and lovastatin attenuated migration and invasion of MDA-MB-231 and BT-20 breast tumor cells in culture. Acquisition of phenotype to express the cancer stem cell marker, CD44, leads to invasive potential of the tumor cells. Interestingly, statins significantly decreased the expression of CD44 protein via a transcri...

Geranylgeranylation Facilitates Proteasomal Degradation of Rho G-Proteins in Human Trabecular Meshwork Cells [Glaucoma]

Investigative Ophthalmology — Fri, 25 Mar 2011 00:00:00 +0100

Conclusions. Posttranslational geranylgeranylation selectively alters the lifecycle of newly synthesized Rho proteins by facilitating their membrane translocation, functional activation, and turnover. Geranylgeranylation represents a novel mechanism by which active Rho proteins are targeted to the proteasome for degradation in human TM cells. (Source: Investigative Ophthalmology)

Statins for the prevention and treatment of infections: a systematic review and meta-analysis

NeLM - Disease Focused Reviews — Mon, 21 Mar 2011 00:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review concluded that statin use may be associated with benefits in treating and preventing infections, but given the heterogeneity between studies and evidence of publication bias, randomised controlled trials are needed to confirm this benefit of statin use. These conclusions are likely to be reliable. [Statins used were atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin and simvastatin.] CRD Commentary: The review question and the inclusion criteria were clear. The authors searched several relevant databases, including one which listed conference abstracts. This, together with the lack of language restrictions, reduced the chances of relevant studies being omitted or biases being introduced. Howev...

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Decrease in Dipeptidyl Peptidase IV Activity is Linked to the Efficacy of Differentiating Compounds in Follicular Thyroid Carcinoma Cell Lines

Hormone and Metabolic Research — Wed, 16 Mar 2011 00:00:00 +0100

Horm Metab ResDOI: 10.1055/s-0031-1273682AbstractMetastasized differentiated thyroid carcinoma is treated by surgery followed by radioiodine remnant ablation. The application of differentiating agents is a possibility of increasing the efficacy of radioiodine therapy. We evaluated DPP IV and aminopeptidase N, both linked to malignancy in thyroid carcinoma, and dipeptidyl peptidase II activities in human follicular thyroid carcinoma cell lines upon treatment with retinol, apicidine, and lovastatin as differentiating agents. Decrease of dipeptidyl peptidase IV (DPP IV) activity may play a role in the differentiating action. In the human cancer cell lines FTC 138 and 238, high DPP IV and low aminopeptidase N activities were recorded. Retinol treatment induced increases in thyroid-specific pro...

Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients

NeLM - Disease Focused Reviews — Tue, 15 Mar 2011 00:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review concluded that statin treatment used for the primary prevention of cardiovascular disease was effective in reducing cardiovascular death and other major cardiovascular events. The conduct and reporting of the review were good and the conclusions are likely to be reliable. [Included studies assessed atorvastatin, fluvastatin, pravastatin and lovastatin.] CRD Commentary: The inclusion criteria for this review were clearly stated. The search was extensive and no language restrictions were applied, thus the possibility of missed studies and the introduction of publication and language biases was reduced. The authors stated that tests showed no evidence of publication bias. The methods used for study selection a...

Demographic determinants of response to statin medications.

American Journal of Health-System Pharmacy : AJHP — Tue, 15 Mar 2011 00:00:00 +0100

Conclusion Lower LDL cholesterol level before treatment, older age, male sex, statin use before CAD diagnosis, the last statin medication used by a patient before the end of the study, higher dosages of simvastatin or lovastatin, and a lower number of medication adjustments were associated with achieving an LDL cholesterol concentration of <100 mg/dL. PMID: 21378299 [PubMed - in process] (Source: American Journal of Health-System Pharmacy : AJHP)

LOVASTATIN (Lovastatin) Tablet [AvKARE, Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Thu, 03 Mar 2011 05:00:00 +0100

Updated Date: Mar 3, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Mevalonate pathway inhibitors affect anticancer drug-induced cell death and DNA damage response of human sarcoma cells

Cancer Letters — Mon, 28 Feb 2011 00:00:00 +0100

Abstract: Lovastatin (Lov), bisphosphonates (BP) and metformin (Met) are widely used drugs, having in common that they interfere with the mevalonate pathway (MP). The MP generates isoprene moieties required for the function of regulatory GTPases controlling cell proliferation and survival. Here, we addressed the question whether MP inhibitors interfere with the anti-tumor efficacy of anticancer drugs. We comparatively analyzed the effect of equitoxic doses of Lov, BP and Met on cell viability, cell cycle progression, apoptosis and DNA damage response (DDR) of human osteo- and fibrosarcoma cells exposed to doxorubicin or cisplatin. We found that Lov, BP and Met modulated the anticancer drug sensitivity of sarcoma cells in an agent-, dose and time-dependent fashion. Mostly, the MP inhibitors...

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Low Level Bacterial Endotoxin Activates Two Distinct Signaling Pathways in Human Peripheral Blood Mononuclear Cells

Journal of Inflammation — Fri, 25 Feb 2011 00:00:00 +0100

Conclusions: These findings suggest that IL-8 release and the respiratory burst are regulated by distinct endotoxin-dependent signaling pathways in PBMC in low level of endotoxin exposure. Selectively modulating these pathways could lead to new approaches to treat chronic inflammatory diseases, such as atherosclerosis, while preserving the capacity of monocytes to respond to acute bacterial infections. (Source: Journal of Inflammation)

Azathioprine-Induced Fever in Sarcoidosis (March).

The Annals of Pharmacotherapy — Tue, 22 Feb 2011 00:00:00 +0100

CONCLUSIONS: The rapid resolution of fever after discontinuation of azathioprine suggests that it was the likely source of fever in this patient. If azathioprine is increasingly prescribed in patients with sarcoidosis, fever as an adverse reaction may become more common. PMID: 21343403 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

Arecoline stimulated Cyr61 production in human gingival epithelial cells: Inhibition by lovastatin

Oral Oncology — Mon, 14 Feb 2011 00:00:00 +0100

In this study, we show that arecoline, a main alkaloid found in AN, stimulated Cyr61 synthesis in human gingival epithelial S–G cells. Constitutive overexpression of Cyr61 protein in oral epithelial cells during AN chewing may play a role in the pathogenesis of oral cancer. ERK inhibitor PD98059, N-acetyl-l-cysteine, Rho-associated protein kinase (ROCK) selective inhibitor Y-27632 and a geranylgeranyltransferase inhibitor reduced the arecoline-stimulated levels of Cyr61 protein by ∼31%, 47%, 65% and 100%, respectively. Lovastatin also completely inhibited arecoline-induced Cyr61 synthesis and the inhibition is dose-dependent. Decreased of geranylgeranylated proteins could be the mechanism that lovastatin regulates Cyr61 synthesis and lovastatin could serve as a useful agent in controll...

ADVICOR (Niacin And Lovastatin) Tablet, Extended Release [Abbott Laboratories]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 11 Feb 2011 05:00:00 +0100

Updated Date: Feb 11, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

A clone-based transcriptomics approach for the identification of genes relevant for itaconic acid production in Aspergillus.

Fungal Genetics and Biology — Fri, 11 Feb 2011 00:00:00 +0100

In this study, a cloned based transcriptomics approach was used to identify genes crucial in the biosynthesis pathway for one of these acids, itaconic acid. From a number of different Aspergillus terreus controlled batch fermentations, those cultures with the largest difference in itaconic acid titer and productivity were selected for mRNA isolation. cDNAs derived from these mRNA samples were used for subsequent hybridization of glass slide arrays based on a collection of 5000 cDNA clones. A selection of 13 cDNA clones resulting in the strongest (>10-fold) differential hybridization signals were identified and subsequently the inserts of these clones were sequenced. Sequence analysis revealed the presence of in total five different gene inserts among the sequenced clones. From one of th...

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May lovastatin target both autism and epilepsy? A novel hypothesized treatment.

Epilepsy and Behaviour — Tue, 25 Jan 2011 00:00:00 +0100

Authors: Ghanizadeh A PMID: 21269887 [PubMed - as supplied by publisher] (Source: Epilepsy and Behaviour)

Genome screening for reducing type I polyketide synthase genes in tropical fungi associated with medicinal plants

World Journal of Microbiology and Biotechnology — Mon, 24 Jan 2011 18:02:52 +0100

Abstract The aim of this work was to employ primers, which encode ketosynthase (KS) domains designed to detect Lovastatin-type PKSs (highly reduced molecules), to identify fungal species that have the potential for polyketide production. Using this strategy we have identified twenty-three KS sequences from twenty different fungal strains associated with medicinal plants found in Thailand. Phylogenetic analysis based on these sequences suggested that rapid screening provided the potential to explore significant PKS structural diversity. With this primer set a unique subclade of reducing type I PKS was identified. This encodes uncharacterized functional enzyme systems, which may suggest a novel function for these pks. Two fungi, Eupenicillium shearii and Myrothecium pandanico...

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents.

Braz J Med Biol Res — Fri, 14 Jan 2011 00:00:00 +0100

Authors: Gonçalves DO, Calou IB, Siqueira RP, Lopes AA, Leal LK, Brito GA, Tomé AR, Viana GS PMID: 21243316 [PubMed - as supplied by publisher] (Source: Braz J Med Biol Res)

Rhadbomyolysis associated with co‐administration of danazol and lovastatin

British Journal of Clinical Pharmacology — Tue, 11 Jan 2011 00:00:00 +0100

(Source: British Journal of Clinical Pharmacology)

Birch bark nutrient prevents obesity, diabetes and high cholesterol

NaturalNews.com — Mon, 10 Jan 2011 07:00:00 +0100

(NaturalNews) Researchers from the Shanghai Institutes for Biological Sciences (SIBC) in China have identified a powerful compound in birch bark called betulin that helps lower cholesterol and prevent both diabetes and obesity. And betulin works particularly better than the statin drug lovastatin at lowering cholesterol, except without the harmful side effects.Dr. Bao-Liang Song and his colleagues from SIBC tested the effects of betulin and found that it specifically targets the genes responsible for making harmful blood fats like triglycerides by effectively lowering their activity and protecting against disease. And since the compound is "abundant in birch bark," it has the potential to revolutionize the way blood fat levels are managed.Concerning cholesterol levels, betulin was shown to...

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Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes in Candida glabrata

Genes to Cells — Wed, 29 Dec 2010 01:19:09 +0100

Zn[2]‐Cys[6] binuclear transcription factors Upc2p and Ecm22p regulate the expression of genes involved in ergosterol biosynthesis and exogenous sterol uptake in Saccharomyces cerevisiae. We identified two UPC2/ECM22 homologues in the pathogenic fungus Candida glabrata which we designated CgUPC2A and CgUPC2B. The contribution of these two genes to sterol homeostasis was investigated. Cells that lack CgUPC2A (upc2AΔ) exhibited enhanced susceptibility to the sterol biosynthesis inhibitors, fluconazole and lovastatin, whereas upc2BΔ‐mutant cells were as susceptible to the drugs as wild‐type cells. The growth of upc2AΔ cells was also severely attenuated under anaerobic conditions. Lovastatin treatment enhanced the expression of ergosterol biosynthetic genes, ERG2 and ERG3 in wild‐ty...

Lactone form 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (statins) stimulate the osteoblastic differentiation of mouse periodontal ligament cells via the ERK pathway

Journal of Periodontal Research — Tue, 28 Dec 2010 00:00:00 +0100

Conclusion: Lovastatin and simvastatin may stimulate the osteoblastic differentiation of periodontal ligament cells via the ERK1/2 pathway. This suggests that the statins may be useful for regenerating periodontal hard tissue. (Source: Journal of Periodontal Research)

Influence of one-year treatment with lovastatin on myocardial remodeling and ischemia in patients with coronary artery disease.

Anadolu Kardiyol Der... — Fri, 24 Dec 2010 00:00:00 +0100

CONCLUSION: Lipid-lowering therapy with lovastatin improved the LV systolic function and decreased myocardial ischemia. PMID: 21183418 [PubMed - as supplied by publisher] (Source: Anadolu Kardiyol Der...)

The effect of lovastatin on oxidative stress and antioxidant enzymes in hydrogen peroxide intoxicated rat.

Food and Chemical Toxicology — Wed, 22 Dec 2010 00:00:00 +0100

Authors: Kumar S, Srivastava N, Gomes J Oxidative stress has been linked to the development of many diseases and hastens the progression of cardiovascular diseases. Since lovastatin is used worldwide as a cholesterol lowering drug, the present study was undertaken to evaluate the antioxidant property of lovastatin against H(2)O(2) induced oxidative stress in rats. Four study groups of rats of four animals each were treated with DMSO (control), H(2)O(2) (OS), lovastatin (L) and H(2)O(2)+lovastatin (OSL). On the 15th day the animals were sacrificed, and the liver and heart tissues were analyzed for oxidative stress biomarkers and anti-oxidant enzymes. Results of the OSL-group showed a reduction in thiobarbituric acid reactive substances in liver (42.7%) and heart tissue (8%) compared wit...

ALTOPREV (Lovastatin) Tablet, Extended Release [Shionogi Pharma, Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Mon, 20 Dec 2010 05:00:00 +0100

Updated Date: Dec 20, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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Novel Extended-Release Formulation of Lovastatin by one-Step Melt Granulation: in-Vitro and in-Vivo Evaluation.

European Journal of Pharmaceutics and Biopharmaceutics — Fri, 17 Dec 2010 00:00:00 +0100

In conclusion, we developed a lovastatin formulation that provided extended plasma levels that confirm that one-step melt granulation in high shear mixer could be an easy and cost-effective technique for extended release formulation development. PMID: 21172434 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)

Abbott subsidiary settles cholesterol drug suit for $41M

Cardiovascular Business News — Thu, 09 Dec 2010 16:40:05 +0100

Kos Pharmaceuticals, a subsidiary of Abbott Laboratories, has agreed to pay more than $41 million to resolve criminal and civil liability arising from conduct relating to its cholesterol drugs niacin XR/lovastatin (Advicor) and niacin (Niaspan), the Department of Justice (DoJ) reported. (Source: Cardiovascular Business News)

Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib

Journal of Cellular Physiology — Tue, 07 Dec 2010 00:00:00 +0100

AbstractEpidermal growth factor receptor (EGFR) is overexpressed in many cancer types including ˜30% of breast cancers. Several small molecule tyrosine kinase inhibitors (TKIs) targeting EGFR have shown clinical efficacy in lung and colon cancers, but no benefit has been noted in breast cancer. Thirteen EGFR expressing breast cancer cell lines were analyzed for response to EGFR TKIs. Seven were found to be EGFR TKI resistant; while shRNA knockdown of EGFR determined that four of these cell lines retained the requirement of EGFR protein expression for growth. Interestingly, EGFR localized to plasma membrane lipid rafts in all four of these EGFR TKI resistant cell lines, as determined by biochemical raft isolation and immunofluorescence. When lipid rafts were depleted of cholesterol using l...

OxLDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signaling

Atherosclerosis — Mon, 06 Dec 2010 00:00:00 +0100

Conclusions: This study provides a new focus for preventive therapy for atherosclerotic disease by delineating a clearer path from OxLDL through the endothelial cell LOX-1 receptor, RhoA, and ROCK, to the activation of arginase II, downregulation of NO, and vascular dysfunction. (Source: Atherosclerosis)

Lovastatin decreases the synthesis of inflammatory mediators in the hippocampus and blocks the hyperthermia of rats submitted to long-lasting status epilepticus.

Epilepsy and Behaviour — Thu, 02 Dec 2010 00:00:00 +0100

Authors: Gouveia TL, Scorza FA, Silva MJ, Bandeira TD, Perosa SR, Argañaraz GA, Silva MD, Araujo TR, Frangiotti MI, Amado D, Cavalheiro EA, Silva JA, Naffah-Mazzacoratti MD Statins may act on inflammatory responses, decreasing oxidative stress and also reducing temperature after a brain ischemic insult. Previous data have indicated that statins protect neurons from death during long-lasting status epilepticus (SE) and attenuate seizure behaviors in animals treated with kainic acid. In this context, the study described here aimed to investigate the effect of lovastatin on body temperature and on mRNA expression levels of hippocampal cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 and B2 receptors of rats submitted to pilocarpine-induced SE. Quan...

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Response surface methodology for lovastatin production by Aspergillus terreus GD13 strain.

Acta Microbiologica et Immunologica Hungarica — Wed, 01 Dec 2010 00:00:00 +0100

Authors: Kaur H, Kaur A, Saini HS, Chadha BS A wild type Aspergillus terreus GD13 strain, chosen after extensive screening, was optimized for lovastatin production using statistical Box-Behnken design of experiments. The interactive effect of four process parameters, i.e. lactose and soybean meal, inoculum size (spore concentration) and age of the spore culture, on the production of lovastatin was evaluated employing response surface methodology (RSM). The model highlighted the positive effect of soybean meal concentration and inoculum level for achieving maximal level of lovastatin (1342 mg/l). The optimal fermentation conditions improved the lovastatin titre by 7.0-folds when compared to the titres obtained under unoptimized conditions. PMID: 21183423 [PubMed - in process] (Sourc...

Cytotoxic effect of different statins and thiazolidinediones on malignant glioma cells

Cancer Chemotherapy and Pharmacology — Tue, 30 Nov 2010 17:48:28 +0100

Conclusion The assessed combination of statins with thiazolidinediones shows a synergistic cytotoxic effect against glioblastoma cells in vitro, which could represent a feasible therapeutic schema. Content Type Journal ArticleDOI 10.1007/s00280-010-1535-2Authors Jorge Humberto Tapia-Pérez, Department of Neurosurgery, Otto von Guericke University Magdeburg, Magdeburg, GermanyElmar Kirches, Department of Neuropathology, Otto von Guericke University Magdeburg, Magdeburg, GermanyChristian Mawrin, Department of Neuropathology, Otto von Guericke University Magdeburg, Magdeburg, GermanyRaimund Firsching, Department of Neurosurgery, Otto von Guericke University Magdeburg, Magdeburg, GermanyThomas Schneider, Department of Neurosurgery, Otto von Guericke University Magdeburg,...

Synergic effect of Eicosapentaenoic acid and Lovastatin on gene expression of HMGCoA reductase and LDL receptor in cultured HepG2 cells

BioMed Central — Tue, 30 Nov 2010 00:00:00 +0100

Conclusions. The use of EPA, in combination with low doses of Lovastatin may have potential value in treatment of neoplastic diseases. (Source: BioMed Central)

Clinical evaluation of Dyslipidemia among type II diabetic patients at Public hospital Penang, Malaysia

International Archives of Medicine — Wed, 24 Nov 2010 00:00:00 +0100

Background: Global views emphasize the need for early; effective intervention against the atherogenic dyslipidemia associated with type 2 diabetes and metabolic syndrome to reduce the risk of premature cardiovascular diseases. Our aim was to determine the clinical practices and compliance among dyslipidemia with type II diabetes and hypertension in multiracial society.Method(s): Study was carried out in out-patient department of General hospital Penang over a period of ten months (Jan - Oct 2008). Study reflects the retrospective data collection covering a period of three years from Jan 2005- Dec 2007. Universal sampling technique was used to select all the patients' undergone treatment for diabetes type II and dyslipidemia. All the concerned approvals were obtained from Clinical research ...

Systematic review: comparative effectiveness and harms of combinations of lipid-modifying agents and high-dose statin monotherapy

NeLM - Disease Focused Reviews — Wed, 24 Nov 2010 00:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review compared high-dose statin monotherapy with combination therapy in adults at high-risk of coronary disease. The authors concluded that there was insufficient evidence to support the benefit of combination therapy for mortality, myocardial infarction, stroke, and revascularisation procedures. The authors' conclusion reflected the evidence presented, but the reliability is potentially compromised by search restrictions and unclear study quality. [he included statins were atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin. The majority of studies examined the statin-ezetimibe combination.] CRD Commentary: The review question was clear and was supported by detailed and potentially r...

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What Combination Therapy with a Statin, If Any, Would You Recommend?

Current Atherosclerosis Reports — Tue, 23 Nov 2010 18:17:00 +0100

Abstract The latest recommended goals for blood lipid levels may require multiple lipid drugs. Lower doses in combination may render more efficacy and safety than highest doses of single agents. Except for isolated hypoalphalipoproteinemia (a low level of high-density lipoprotein cholesterol), therapies will start with a statin. All marketed statins are acceptable. The choice may be based on dose- efficacy and patient’s tolerability. High-potency statins (eg, atorvastatin, simvastatin, or rosuvastatin) are often chosen. Currently, generic statins, such as simvastatin, lovastatin, pravastatin, and fluvastatin, offer cost benefits. The choice of added agent depends on the “residual lipoprotein abnormalities” after statin therapy, efficacy, compliance issues, and cost. ...

ADVICOR (Niacin And Lovastatin) Tablet, Extended Release [Abbott Laboratories]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Tue, 23 Nov 2010 05:00:00 +0100

Updated Date: Nov 23, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Statins Promote the Clearance of A{beta} by IDE [Lipids]

Journal of Biological Chemistry — Fri, 19 Nov 2010 00:00:00 +0100

Epidemiological studies indicate that intake of statins decrease the risk of developing Alzheimer disease. Cellular and in vivo studies suggested that statins might decrease the generation of the amyloid β-peptide (Aβ) from the β-amyloid precursor protein. Here, we show that statins potently stimulate the degradation of extracellular Aβ by microglia. The statin-dependent clearance of extracellular Aβ is mainly exerted by insulin-degrading enzyme (IDE) that is secreted in a nonconventional pathway in association with exosomes. Stimulated IDE secretion and Aβ degradation were also observed in blood of mice upon peripheral treatment with lovastatin. Importantly, increased IDE secretion upon lovastatin treatment was dependent on protein isoprenylation and up-regul...

Sterol Regulatory Element-Binding Protein 2 (SREBP2) Activation after Excess Triglyceride Storage Induces Chemerin in Hypertrophic Adipocytes.

Endocrinology — Wed, 17 Nov 2010 00:00:00 +0100

In conclusion, the current data show that adipocyte hypertrophy and chronic inflammation are equally important in inducing chemerin synthesis. PMID: 21084441 [PubMed - as supplied by publisher] (Source: Endocrinology)

LOVASTATIN (Lovastatin) Tablet [REMEDYREPACK INC. ]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Tue, 02 Nov 2010 05:00:00 +0100

Updated Date: Nov 2, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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Statins Use in Presence of Elevated Liver Enzymes: What to Do?

Clinical Cases and Images — Fri, 29 Oct 2010 13:17:00 +0100

The beneficial role of statins in primary and secondary prevention of coronary heart disease has resulted in their frequent use in clinical practice.However, safety concerns, especially regarding hepatotoxicity, have driven multiple trials, which have demonstrated the low incidence of statin-related hepatic adverse effects. The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis, in which liver enzyme levels are elevated in the absence of proven hepatotoxicity."Ttransaminitis" is usually asymptomatic, reversible, and dose-related.Lovastatin, a compound isolated from Aspergillus terreus, was the first statin to be marketed for lowering cholesterol. Image source: Wikipedia, public domain.The increasing incidence of chronic liver diseases, including nonalcoh...

"Statin" Levels Vary Wildly in Red Yeast Rice

Medscape Medical News Headlines — Wed, 27 Oct 2010 15:29:46 +0100

Red-yeast-rice extract contains the compound that became lovastatin and related ones, but how much is in a capsule depends on the manufacturer. Heartwire (Source: Medscape Medical News Headlines)

"Statin" levels vary wildly in red yeast rice

theHeart.org — Tue, 26 Oct 2010 13:30:00 +0100

Red-yeast-rice extract contains the compound that became lovastatin and related ones, but how much is in a capsule depends on the manufacturer. For complete story visit theheart.org. (Source: theHeart.org)

Wide Variations Found in Red Yeast Rice Products (CME/CE)

MedPage Today Cardiovascular — Mon, 25 Oct 2010 20:00:00 +0100

(MedPage Today) -- Laboratory analyses have found wide variations in the amount of active compounds known as monacolins -- related to the prescription drug lovastatin -- in different brands of the popular dietary supplement red yeast rice. (Source: MedPage Today Cardiovascular)

Marked Variability of Monacolin Levels in Commercial Red Yeast Rice Products: Buyer Beware! [Original Investigation]

Archives of Internal Medicine — Sun, 24 Oct 2010 23:00:00 +0100

Conclusions We found striking variability in monacolin content in 12 proprietary RYR products and the presence of citrinin in one-third of the formulations tested. Although RYR may have potential as an alternative lipid-lowering agent, our findings suggest the need for improved standardization of RYR products and product labeling. Until this occurs, physicians should be cautious in recommending RYR to their patients for the treatment of hyperlipidemia and primary and secondary prevention of cardiovascular disease. (Source: Archives of Internal Medicine)

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Lovastatin Enhances Paraoxonase Enzyme Activity and Quells Low Density Lipoprotein Susceptibility to Oxidation in Type 2 Diabetic Nephropathy.

Clinical Biochemistry — Tue, 19 Oct 2010 23:00:00 +0100

CONCLUSIONS: Lovastatin therapy improves PON1 and ARE activities, and LDL-C susceptibility to oxidation. Despite withdrawal of lovastatin, PON1 and ARE activities, and LDL-C susceptibility to oxidation remain unchanged in people with T2DN. PMID: 20970413 [PubMed - as supplied by publisher] (Source: Clinical Biochemistry)

When it comes to health knowledge, doctors are surprisingly ignorant

NaturalNews.com — Mon, 11 Oct 2010 07:00:00 +0100

(NaturalNews) America is a nation of widespread health and nutritional illiteracy. And I'm not just talking about the knowledge gaps of health consumers, either. It's the doctors and health "experts" who have astonishing gaps in knowledge that should be considered basic health information in any first-world nation.Parents, too, lack any real literacy in nutrition and health. That's largely because medical journals, health authorities and the mass media actively misinform them about health and nutrition issues, hoping to prevent people from learning how to take care of their own health using simple, natural remedies and cures.Here are some shocking examples of the huge gaps in knowledge among doctors, parents and others...What your doctor doesn't know might actually harm you• Most doct...

Polyunsaturated liposomes are antiviral against hepatitis B and C viruses and HIV by decreasing cholesterol levels in infected cells [Cell_Biology]

Proceedings of the National Academy of Sciences — Tue, 05 Oct 2010 16:48:12 +0100

The pressing need for broad-spectrum antivirals could be met by targeting host rather than viral processes. Cholesterol biosynthesis within the infected cell is one promising target for a large number of viral systems, including hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. Liposomes developed for intracellular, endoplasmic reticulum (ER)-targeted in vivo drug delivery have been modified to include polyunsaturated fatty acids that exert an independent antiviral activity through the reduction of cellular cholesterol. These polyunsaturated ER liposomes (PERLs) have greater activity than lovastatin (Mevacor, Altoprev), which is clinically approved for lowering cholesterol and preventing cardiovascular disease. Treatment of HCV, HBV, and HIV infections with PERLs significantly decr...

Lovastatin Promotes Redifferentiation of Human Nucleus Pulposus Cells During Expansion in Monolayer Culture

Artificial Organs — Thu, 30 Sep 2010 22:00:58 +0100

Abstract (Source: Artificial Organs)

Membrane raft association of the Vpu protein of human immunodeficiency virus type 1 correlates with enhanced virus release.

Virology — Sun, 26 Sep 2010 23:00:00 +0100

In this study, we analyzed whether the Vpu protein is associated with microdomains known as lipid or membrane rafts. Our results indicate that Vpu partially partitions into detergent-resistant membrane (DRM) fractions when expressed alone or in the context of simian-human immunodeficiency virus (SHIV) infection. The ability to be partitioned into rafts was observed with both subtype B and C Vpu proteins. The use of cholesterol lowering lovastatin/M-Î²-cyclodextrin and co-patching experiments confirmed that Vpu can be detected in cholesterol rich regions of membranes. Finally, we present data showing that raft association-defective transmembrane mutants of Vpu have impaired enhanced virus release function, but still maintain the ability to down-regulate CD4. PMID: 20880565 [PubMed - a...

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Use of statins and risk of haematological malignancies: a meta-analysis of six randomized clinical trials and eight observational studies

NeLM - Disease Focused Reviews — Tue, 21 Sep 2010 23:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: The authors concluded that the potential role for statin therapy in the prevention of haematological malignancies was not supported with the meta-analysis. Despite some minor limitations, this conclusion appears to reflect the evidence presented and is likely to be reliable. [Statin agents included fluvastatin, lovastatin, pravastatin and simvastatin.] CRD Commentary: The review question was supported by clear inclusion criteria. The literature search included only two databases. It is not known whether this search was restricted by language, but the authors did assess the likelihood of publication bias. Methods for data extraction were likely to minimise the possibility of reviewer error or bias, but the authors did n...

Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis

NeLM - Disease Focused Reviews — Tue, 21 Sep 2010 23:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review assessed the efficacy and safety of statin therapy in children and adolescents for the treatment of hypercholesterolaemia. The authors concluded that statin mono-therapy was efficacious and well tolerated in the short-term. Despite some limitations, the authors' conclusions appear to follow from the results presented. [Interventions included in the review were: pravastatin, simvastatin, lovastatin, atorvastatin.] CRD Commentary: The review was supported by clear inclusion criteria and several databases were searched for relevant studies. The search was not restricted by language, although the authors do not appear to have assessed the possibility of publication bias. Methods used to select studies and extra...

Lovastatin Inhibits Gap Junctional Communication in Cultured Aortic Smooth Muscle Cells

Journal of Cardiovascular Pharmacology and Therapeutics — Thu, 09 Sep 2010 22:05:21 +0100

Conclusions: These results suggest that lovastatin inhibits migration in a dose-dependent manner by attenuating JIC. Suppression of gap junction function could add another explanation of statin-induced antiproliferative effect. (Source: Journal of Cardiovascular Pharmacology and Therapeutics)

Cholesterol drug may block arthritis

NHS News Feed — Wed, 08 Sep 2010 17:04:00 +0100

Conclusion This large cohort study has established a link between longer use of statins and a reduced risk of rheumatoid arthritis and osteoarthritis. It should be noted that the study compared the incidence of rheumatoid arthritis in people taking different amounts of statins, but did not assess arthritis risk in people who did not use statins. Therefore, this study cannot tell us whether taking the drugs is better at preventing rheumatoid arthritis than taking no statins at all. The study’s design had a number of potential limitations: It is not clear whether the study took into account all possible confounding factors (those linked to the exposure and outcome). One important potential confounder is the cholesterol-lowering action of statin drugs. Lower rates of rheumatoid arthrit...

Statin drugs may block arthritis

NHS News Feed — Wed, 08 Sep 2010 17:04:00 +0100

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ADVICOR (Niacin And Lovastatin) Tablet, Extended Release ADVICOR (Niacin And Lovastatin) Tablet, Film Coated [Physicians Total Care, Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Tue, 07 Sep 2010 05:00:00 +0100

Updated Date: Sep 7, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

The Effect of Nitric Oxide and Statins on Thrombospondin-1-Induced Chemotaxis in Vascular Smooth Muscle Cells

Journal of Vascular Surgery — Tue, 31 Aug 2010 23:00:00 +0100

Vascular smooth muscle cell (VSMC) chemotaxis is important in intimal hyperplasia (IH). Nitric oxide (NO), a diffusible molecule that decreases VSMC chemotaxis to several growth factors, is protective against IH. Thrombospondin-1 (TSP-1), a matricellular glycoprotein that induces VSMC chemotaxis, acts antagonistically to NO in VSMCs. Statins exhibit direct and pleiotropic effects on VSMCs. We showed overnight treatment with lovastatin inhibited TSP-1-induced VSMC chemotaxis by mevalonate pathway inhibition and was Ras dependent. Hypothesis: Short-term statin treatment will inhibit TSP-1-induced VSMC chemotaxis and NO donors will enhance statin inhibitory effects. (Source: Journal of Vascular Surgery)

Detailed Molecular Fingerprinting of Four New Anaplastic Thyroid Carcinoma Cell Lines and Their Use for Verification of RhoB as a Molecular Therapeutic Target.

The Journal of Clinical Endocrinology and Metabolism — Tue, 31 Aug 2010 23:00:00 +0100

Conclusions: Molecular descriptions of thyroid lines were matched to the originating tumors, setting a new standard for cell line characterization. Furthermore, suppressed RhoB is implicated as a molecular target for therapy against ATC because five classes of drugs up-regulate RhoB and inhibit growth dose-responsively. PMID: 20810568 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)

Lovastatin raises serum osteoprotegerin level in people with type 2 diabetic nephropathy.

Clinical Biochemistry — Tue, 17 Aug 2010 23:00:00 +0100

CONCLUSIONS: Lovastatin therapy increased serum OPG level and decreased sRANKL level in people with T2DN. The withdrawal of lovastatin decreased serum OPG level, while sRANKL level was extensively increased. PMID: 20727867 [PubMed - as supplied by publisher] (Source: Clinical Biochemistry)

Amiodarone/lovastatin interaction: Dark urine, weakness and aches: case report

Reactions — Fri, 13 Aug 2010 05:47:51 +0100

(Source: Reactions)

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Lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma and neuroblastoma cells: enhanced differentiation and apoptosis in combination with dbcAMP.

Molecular and Cellular Biochemistry — Sun, 08 Aug 2010 23:00:00 +0100

This study suggests the potential of combining these therapeutic approaches in EC and NB patients. PMID: 20694854 [PubMed - as supplied by publisher] (Source: Molecular and Cellular Biochemistry)

Cholesterol Biosynthesis Pathway Intermediates and Inhibitors Regulate Glucose-Stimulated Insulin Secretion and Secretory Granule Formation in Pancreatic {beta}-Cells.

Endocrinology — Tue, 03 Aug 2010 23:00:00 +0100

In this study, we examined the involvement of cholesterol biosynthesis intermediates and inhibitors in insulin secretion and SG formation mechanisms. There are two routes for the supply of cholesterol to the cells: one via de novo biosynthesis and the other via low-density lipoprotein receptor-mediated endocytosis. We found that insulin secretion and content are diminished by beta-hydroxy-beta-methylglutaryl-coenzyme A inhibitor lovastatin but not by lipoprotein depletion from the culture medium in MIN6 beta-cells. Cholesterol biosynthesis intermediates mevalonate, squalene, and geranylgeranyl pyrophosphate enhanced glucose-stimulated insulin secretion, and the former two increased insulin content. The glucose-stimulated insulin secretion-enhancing effect of geranylgeranyl pyrophosphate wa...

Mevacor (Lovastatin) - updated on RxList

RxList - New and Updated Drug Monographs — Mon, 26 Jul 2010 07:00:00 +0100

Mevacor (Lovastatin) drug description - FDA approved labeling for prescription drugs and medications at RxList (Source: RxList - New and Updated Drug Monographs)

Effects of fungal statins on high-glucose-induced mouse mesangial cell hypocontractility may involve filamentous actin, t-complex polypeptide 1 subunit beta, and glucose regulated protein 78.

Translational Research : the journal of laboratory and clinical medicine — Tue, 20 Jul 2010 07:12:13 +0100

In conclusion, Sim and Lov both seem to reverse mesangial cell hypocontractility. The process of Sim reversal of mesangial cell hypocontractility may involve F-actin, TCP-1beta, and GRP78. PMID: 20627192 [PubMed - in process] (Source: Translational Research : the journal of laboratory and clinical medicine)

Statins: 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) Reductase Inhibitors Demonstrate Anti-Atherosclerotic Character due to Their Antioxidant Capacity.

Applied Biochemistry and Biotechnology — Fri, 16 Jul 2010 23:00:00 +0100

This study revealed the importance of lovastatin and simvastatin to prevent oxidative stress-related cardiovascular diseases. PMID: 20640529 [PubMed - as supplied by publisher] (Source: Applied Biochemistry and Biotechnology)

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Study shows how memory is disrupted in those with disease linked to learning disabilities

UCLA Newsroom: Health Sciences — Thu, 15 Jul 2010 22:10:00 +0100

Imagine if your brain lost its working memory — the ability to hold and manipulate information in your mind's eye. That's the plight faced by millions of people with neurofibromatosis type 1, or NF1. The genetic condition affects one in 3,500 people and is the most common cause of learning disabilities. Now a UCLA research team has uncovered new clues about how NF1 disrupts working memory. Published in the July 12 online edition of Proceedings of the National Academy of Sciences, the findings suggest a potential drug target for correcting NF1-related learning disabilities. NF1 is caused by mutations in a gene called neurofibromin, or Nf1, which makes a protein with the same name. Previous mouse studies led by principal investigator Dr. Alcino Silva, a professor of...

MEVACOR (Lovastatin) Tablet [Merck Sharp Dohme Corp.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 09 Jul 2010 05:00:00 +0100

Updated Date: Jul 9, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Gluconic acid production by Aspergillus terreus

Letters in Applied Microbiology — Thu, 08 Jul 2010 23:00:00 +0100

Conclusions: A novel pathway of glucose catabolism was demonstrated in A. terreus, a species whose wild type is, without any strain development, capable of producing gluconic acid at high molar conversion efficiency (up to 0·7 mol mol[minus]1 glucose consumed).Significance and Impact of the Study: Aspergillus terreus is a potential novel producer organism for gluconic acid, a compound with many uses as a bulk chemical. With a new knowledge of glucose catabolism by A. terreus, fermentation strategies for secondary metabolite production can be devised with glucose feeding using feedback regulation by pH. (Source: Letters in Applied Microbiology)

ALTOPREV (Lovastatin) Tablet, Extended Release [Shionogi Pharma, Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Thu, 01 Jul 2010 05:00:00 +0100

Updated Date: Jul 1, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Red yeast rice stimulates osteoblast proliferation and increases alkaline phosphatase activity in MC3T3-E1 cells

Nutrition Research — Wed, 30 Jun 2010 23:00:00 +0100

Abstract: Red yeast (Monascus purpureus) is used as a traditional hypocholesterolemic dietary food component in Asia due to its bioactive component, lovastatin. Recently, new evidence suggesting that the statins in red yeast enhance bone formation has been reported, but more research is still needed in order to support these claims of osteogenic effects. Therefore, in this study, we hypothesized that red yeast rice (in which red yeast is fermented) can improve osteogenic function through osteoblast cell proliferation and differentiation. We studied the effect of methanol extract of red yeast rice powder (RYRP) on osteoblast proliferation and differentiation by measuring mitochondrial enzyme activity and bone marker alkaline phosphatase (ALP) activity, respectively. Osteoblast-like MC3T3-E1...

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Effect of fluvastatin, lovastatin, nifedipine and verapamil on the systemic exposure of nateglinide in rabbits

Biopharmaceutics and Drug Disposition — Wed, 30 Jun 2010 23:00:00 +0100

(Source: Biopharmaceutics and Drug Disposition)

Effects of lovastatin on the pharmacokinetics of nicardipine in rats

Biopharmaceutics and Drug Disposition — Wed, 30 Jun 2010 23:00:00 +0100

Abstract (Source: Biopharmaceutics and Drug Disposition)

Activation of PPAR-[gamma] and PTEN cascade participates in lovastatin-mediated accelerated differentiation of oligodendrocyte progenitor cells

Glia — Tue, 22 Jun 2010 23:00:00 +0100

Previously, we and others documented that statins including-lovastatin (LOV) promote the differentiation of oligodendrocyte progenitor cells (OPCs) and remyelination in experimental autoimmune encephalomyelitis (EAE), an multiple sclerosis (MS) model. Conversely, some recent studies demonstrated that statins negatively influence oligodendrocyte (OL) differentiation in vitro and remyelination in a cuprizone-CNS demyelinating model. Therefore, herein, we first investigated the cause of impaired differentiation of OLs by statins in vitro settings. Our observations indicated that the depletion of cholesterol was detrimental to LOV treated OPCs under cholesterol/serum-deprived culture conditions similar to that were used in conflicting studies. However, the depletion of geranylgeranyl-pp under ...

Impact of linoleic acid supplementation on lovastatin production in Aspergillus terreus cultures.

Applied Microbiology and Biotechnology — Tue, 22 Jun 2010 23:00:00 +0100

This study therefore demonstrates for the first time the potential of an oxylipin molecule as an enhancer of a fungal secondary metabolite production with positive impact for industrial exploitation. PMID: 20571794 [PubMed - as supplied by publisher] (Source: Applied Microbiology and Biotechnology)

Cholesterol depletion affects infectivity and stability of pseudorabies virus.

Virus Research — Mon, 21 Jun 2010 23:00:00 +0100

Authors: Desplanques AS, Pontes M, De Corte N, Verheyen N, Nauwynck HJ, Vercauteren D, Favoreel HW Statins, such as lovastatin, inhibit the cellular cholesterol biosynthesis. Addition of lovastatin to SK cells and subsequent infection with the alphaherpesvirus pseudorabies virus (PRV) did not affect the intracellular production of viral structural proteins but reduced virus titers. Addition of methyl-beta-cyclodextrin to deplete cholesterol from the viral envelope also resulted in reduced virus titers. Addition of exogenous cholesterol restored virus titers in both experimenal assays. Further analysis showed that reducing cholesterol levels reduced both the infectivity of newly produced infectious virus and their stability, as assessed by determining virus titers immediately after trea...

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Lovastatin inhibits EGFR dimerization and AKT activation in squamous cell carcinoma cells: potential regulation by targeting rho proteins

Oncogene — Sun, 20 Jun 2010 23:00:00 +0100

Authors: T T Zhao, B G Le Francois, G Goss, K Ding, P A Bradbury & J Dimitroulakos (Source: Oncogene)

Effects of fungal statins on high-glucose-induced mouse mesangial cell hypocontractility may involve filamentous actin, t-complex polypeptide 1 subunit beta, and glucose regulated protein 78

Translational Research — Sun, 20 Jun 2010 23:00:00 +0100

In conclusion, Sim and Lov both seem to reverse mesangial cell hypocontractility. The process of Sim reversal of mesangial cell hypocontractility may involve F-actin, TCP-1β, and GRP78. (Source: Translational Research)

Tumor specific low pH environments enhance the cytotoxicity of lovastatin and cantharidin

Cancer Letters — Thu, 17 Jun 2010 23:00:00 +0100

Abstract: In tumor cell masses, the extracellular pH decreases below 6.5. The effect of external acidic pH on the efficacy of 24 chemical compounds including molecular-targeted inhibitors and anti-tumor reagents was investigated in human cancer cells. Lovastatin showed no cytotoxicity in mesothelioma or pancreatic carcinoma cells at concentrations up to 10μM and pH around 7.4, but 10μM lovastatin decreased the survival of these cells below 40% at acidic pH. Lovastatin inhibits HMG-CoA reductase, resulting in a decrease in the levels of cholesterol and prenylated proteins. An inhibitor of the former pathway showed pH-independent cytotoxic activity, whereas an inhibitor of the latter pathway had stronger activity at acidic pH. The inhibitory efficacy of cantharidin also increased at acidic...

Lovastatin induces VSMC differentiation through inhibition of Rheb and mTOR

AJP: Cell Physiology — Wed, 16 Jun 2010 23:16:41 +0100

In conclusion, these findings illustrate a mechanism for the cardioprotective effects of lovastatin through inhibition of Rheb and mTORC1 and promotion of a differentiated VSMC phenotype. (Source: AJP: Cell Physiology)

Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

Journal of Biomedicine and Biotechnology — Wed, 16 Jun 2010 15:05:20 +0100

In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts. (Source: Journal of Biomedicine and Biotechnology)

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Immunomodulatory Effects of IFN-β and Lovastatin on Immunophenotype of Monocyte-Derived Dendritic Cells in Multiple Sclerosis

Archivum Immunologiae et Therapiae Experimentalis — Mon, 07 Jun 2010 16:04:39 +0100

Abstract Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and current MS treatment is only partially effective. Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate their role in MS, we analyzed the in vitro effects of interferon (IFN)-β and lovastatin on the differentiation and maturation of monocyte-derived dendritic cells (DCs) of MS patients. Twenty-seven patients with relapsing–remitting MS were recruited for the study. DC differentiation and maturation were evaluated based on surface phenotypic changes and the expressions of CD14, CD83, CD1a, CD80, CD86, CD206, and C209 were analyzed by flow cytometry. The results showed that IFN-β and lovastatin affect DC phenotype. Both agents decrease the ex...

Lovastatin: a new weapon against plague?

ScienceDaily Headlines — Fri, 04 Jun 2010 04:00:00 +0100

An experimental study has revealed that lovastatin, a drug prescribed for the treatment of hypercholesterolemia, protects animals against the deadly effects of plague. This infectious disease is on the upsurge in parts of the world. These results obtained by scientists at the Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (CNRS/Université Aix-Marseille 2) have been published in the journal PLoS ONE. (Source: ScienceDaily Headlines)

Do Statins Beneficially or Adversely Affect Glucose Homeostasis?

Current Vascular Pharmacology — Thu, 27 May 2010 23:00:00 +0100

Authors: Kostapanos MS, Liamis GL, Milionis HJ, Elisaf MS The effect of statin treatment on glucose metabolism and the risk of diabetes remains an issue of controversy. Since statins are drugs commonly prescribed for the prevention of cardiovascular disease even in patients with prediabetes or diabetes, it is of great importance to identify the role of statin treatment on glucose homeostasis. In this review, we have scrutinized available data with regard to the effect of every drug of the class on glycemic outcomes. Experimental data describing mechanisms through which these drugs potentially modify the metabolism of carbohydrates have been described. In order to identify statins which may be preferentially used to improve parameters of glycemic control, studies comparing different age...

Systematic review: Statins do not prevent fracture in postmenopausal women

NeLM - News — Tue, 25 May 2010 23:00:00 +0100

Source: Menopause Area: News According to a systematic review of randomised controlled trials, statins do not reduce fracture risk or increase bone mineralisation in postmenopausal women. To determine whether statins can prevent fractures in postmenopausal women, the investigators indentified trials assessing the effect of statins on bone mineral density (BMD). Six randomised trials published between 2001 and 2004 involving 3,022 participants met the inclusion criteria. Four trials (lasting from 2 to 12 months) reported bone turnover markers, two lasting for a year reported BMD, and two with at least 5 years of follow up reported fracture risk. Two trials studied atorvastatin and the other four trials each studied fluvastatin, simvastatin, lovastatin and pravastatin as single t...