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OTHER PUBLICATIONS Imre Kovcs, Albert Csszr, Jnos Tth, Gyrgy Siller, Attila Farkas, Jeni Tarjn, Judit Horvth, Akos Koller Correlation between flow-mediated dilation and erectile dysfunction, European Urology, submitted 2007 IF: 3.542 Erika Toth, Zsolt Bagi, Janos Toth, Anita Racz, Pawel M. Kaminski, Michael S. Wolin, Akos Koller Role of polyol pathway in development of oxidative stress-induced dysfunction of arterioles. Role of diminished NO and enhanced PGH2 TXA2 mediation American Journal of Physiology Submitted IF: 3.560 Kovacs Imre, Csaszar Albert, Koller Akos, Farkas Attila, Horvath Judit, Toth Janos, Tarjan Jeno, Nagy Lajos Pleiotrop effects of atorvastatin for the arterial endothelial function in patients with primer hypercholesterinaemia Cardiologia Hungarica 2004; 34: 114-119.
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Women aged 35 and 51 years ; had received gonadotrophin-releasing hormone GnRH ; agonist therapy for 3 months before surgery. The remaining five women had regular menstrual cycles of 2830 days and had not received any hormonal therapy or ovarian suppression for at least 3 months before surgery. The ovarian tissue was obtained at different phases of the menstrual cycle; during the follicular phase in one subject and during the luteal phase in the others. Microscopic examination demonstrated no growing follicles in the tissue obtained from two women aged 28 and 51 years ; , while in the tissue obtained from the remaining five women, follicles or corpora lutea of 514 mm in diameter were observed. Ovarian tissue was rinsed with saline to remove all visible evidence of blood. After absorption of excess saline, the tissue was stored at 80C until assayed. Informed consent was obtained from all subjects. The protocol was approved by the human research committee of St. Marianna University School of Medicine, Kawasaki, Japan, for instance, atorvastatin india.
Anti-hypertensive drug Lozap losartan ; , the lipid lowering agent Torvacard atorvastatin ; and the CHC drug Ibalgin ibuprofen ; . The key promoted brands which achieved good sales growth in 2007, in the Czech market, were Lozap, Torvacard, Helicid and the cardiovascular drug Lindaxa sibutramine ; which was introduced in 2006. Zentiva launched two new products in the Czech market in 1st Quarter 2007, the anti-migraine drug Cinie sumatriptan ; and the CNS drug Argofan venlafaxin ; . Romania Romania, Zentiva's second largest market in terms of sales, has benefited from the launch of a growing number of the Company's internationally recognized brands. During the 1st Quarter 2007, Zentiva's Romanian business made further progress, recording sales of CZK 657.1 million, 27.2% ahead of the level achieved in 1st Quarter 2006. In local currency terms the overall growth in 1st Quarter 2007 was 22.5%. During this period the brands of the former Sicomed contributed CZK 379.0 million to our sales in Romania, 57.7% of the total. Promoted brands accounted for 70.4% of Romanian sales in 1st Quarter 2007. Amongst Zentiva's top international promoted brands that have done well in Romania are the cardiovascular drug Simvacard simvastatin ; , the antibiotic Azitrox azithromycin ; , the antipsychotic drug Rispen risperidon ; , the pain killer Tralgit tramadol ; and the urological drug Fokusin tamsulosin ; . The largest contributors to sales amongst the company's established local brands, most of which are CHC products, were Algocalmin metamizol ; , the analgesic Antinevralgic P paracetamol, codeine and aspirin ; and Dicarbocalm antiacid ; . Zentiva launched three new cardiovascular products in the Romanian market in 1st Quarter 2007, Zenra ramipril ; , Lindaxa sibutramin ; and Amyx glimepirid ; . Poland Zentiva continued its growth in Poland in 1st Quarter 2007 with sales increasing 13.4% to CZK 513.8 million. Promoted brands accounted for 94.1% of sales in the first three months of 2007 vs. 94.9% in 1st Quarter 2006. In local currency terms Zentiva's sales increased by 16.6% in 1st Quarter 2007 making the Company the fastest growing of the top twenty pharmaceutical companies in Poland. First quarter 2007 growth was due to the continued success of the urology products Penester finasteride ; , Zoxon doxazosine ; , the anti-ulcer drug Helicid omeprazole ; , the antibiotic Azitrox azithromycin ; , as well as a significant contribution by the lipid lowering drug Simvacard simvastatin ; . Simvacard is one of the leading selling lipid lowering drugs in the Polish market and Zentiva's second most important brand in this country. Zentiva's position in the statin market has been enhanced by the success of the more recently introduced lipid lowering drug Torvacard atorvastatin ; . Important contributions to sales were also made by the recently introduced urology drug Fokusin tamsulosin ; , the cardiovascular drug Lozap losartan ; and painkiller Coxtral nimesulide ; . Zentiva launched three new products in the Polish market in 1st Quarter 2007, the cardiovascular drug Amyx glimepirid ; , the anti-migraine drug Cinie sumatriptan ; and the CNS drug Neurol SR alprazolam ; . Slovakia In 1st Quarter 2007, Zentiva increased its sales by 14.0% to CZK 518.3 million. In local currency terms, 1st Quarter 2007 sales in Slovakia increased by 6.6% to SKK 635.1 million. This has been achieved by focusing on maximizing the sales volume of our promoted brands. Promoted brands accounted for 57% of Zentiva's Slovakian sales in 1st Quarter 2007 vs. 55% in the same period in 2006. During the period sales of Zentiva's promoted brands performed well increasing sales by 18.2% while non-promoted brands achieved an 8.8% sales increase!
Lescol. See Fluvastatin Levalbuterol, for asthma, 2122 Levemir. See Insulin detemir Levsin. See Hyoscamine Lexiva. See Fosamprenavir Librium. See Chlordiazepoxide Lifeline AED. See Automated external defibrillators AEDs ; LifePak. See Automated external defibrillators AEDs ; Linezolid, for MRSA infections, 13t Lipitor. See Atorvastatin Loestrin 24 Fe, Loestrin Fe 1 20, for oral contraception, 77t Lopinavir ritonavir, for HIV, 75t Lortab. See Hydrocodone, combination drugs Lovastatin, and other statins, 1 LPV RTV. See Lopinavir ritonavir Lubiprostone, for constipation, 4748 Lucentis. See Ranibizumab.
| Atorvastatin orderLast year. As a result of the Russian government's difficulties in funding the Country's emerging reimbursement system DLO ; Zentiva's sales to this segment of the market have continued to decline in importance since the second half of 2006. In the first half of 2007 sales to the DLO represented only 14% of sales vs. almost 40% in the same period in 2006. The shrinking share of sales in DLO was more than offset by a strong performance in "private" market of our Rx and CHC portfolio growing 55% yoy. The most significant contributors to Zentiva's sales in the first half of 2007 were the antihypertensive drug Lozap losartan ; , the lipid lowering drug Torvacard atorvastatin ; and the urology drug Zoxon doxazosine ; , which is used to treat benign prostatic hypertrophy. Important contributions to sales were also made by the recently introduced urology drug Fokusin tamsulosin ; and anti-hypertensive Coronal bisoprolol ; . Within the CHC segment the nasal decongestant Pinosol, the antimycotic Mycomax fluconazole ; and antihistamine product Zodac cetirizine ; were important contributors to Zentiva's increased sales. Commercial team headcount was 287 at the end of the first half of 2007 vs. 227 at the end of the same period last year. Zentiva received 5 new marketing authorizations in the first half of 2007. Other Markets In addition to its five core markets, Zentiva has been rapidly developing its business in a number of other important countries in Central and Eastern Europe. In aggregate these markets now generate 8% of total pharma sales. In the first half of 2007 growth was achieved in the Ukraine with sales up 21.8% to CZK 170.1 million, the Baltic States with sales up 45.8% to CZK 136.4 million and the other markets of the CIS, where sales grew by 69.7% to CZK 82.8 million. Our sales in Bulgaria declined by 45.1% to CZK 51.2 million in the first half of 2007. This was due to the continued impact of the significant to-market deliveries, which were made in the final quarter of 2006 ahead of the EU entry. Sales in Hungary, our new territory reached CZK 89.2 million, during the period. The growth in these areas along with the progress that has been made in Romania, confirms Zentiva's business strategy of expanding into these newly emerging pharmaceutical markets in the region. Sales by Product Group in CZKm ; Pharmaceuticals Prescription CHC API Other Sales * Gross Sales Sales deductions Net Sales Three Months to June 30 2007 3, ; 3, 418.9 2006 ; 3, 264.8 change 6.8% 4.5% 16.2% ; 6.2% 32.1% 4.7% Six Months to June 30 2007 6, ; 6, 796.6 2006 ; 6, 441.2 change 8.7% 6.8% 15.8% ; 7.6% 54.3% 5.5.
UNEDITED PRE-PUBLICATION OC107 Adherence to Mediterranean diet across the adult population of Symi aged 18-84. By K. JONES1, B. ELLAHI1 and C. ANDROUHARA2 1University of Chester, Parkgate Road, Chester, CH1 4BJ UK, 2 Symi Health Centre, Yialos, Island of Symi, Greece Adherence to a Mediterranean diet MD ; was related to a lower mortality rate for CHD 1 ; . A crosssectional survey on a random sample of the adult Symiot population 18-84 years ; was undertaken to examine the dietary patterns with a focus on adherence to the MD. A two part self reported diet habits and lifestyle questionnaire, incorporating socio demographic questions and a food frequency questionnaire was used to assess adults. Questionnaires n 113 ; , 27% n 30 ; male 63% n 83 ; female ; were coded and analysed using SPSS version 14. BMI self reported ; means were 27kg m 3.99 ; males and 25kg m 5.19 ; females. Prevalence of smoking was low, 76% non smokers n 86, with n 2 non reporters ; . 13% n 15 ; were male and 9% n 10 ; female smokers. Daily physical activity of 15-30 minutes was highest amongst females aged 2544 years. Food habits were compared to the Greek adult population dietary guidelines and the Mediterranean dietary pyramid in Table 1. The dietary pattern observed is largely in harmony with the recommended servings for the Greek adult population and consistent with a MD. Oily fish, olive oil and fruit consumption were typical of recommendations. However, consumption patterns are characterised by a high frequency of red meat. Significant differences in the consumption of energy dense foods within the age groups was observed, with a tendency for the 18-24 and 35-44 year olds having preference for these foods. The older generation 65-84 ; do not show this tendency. Self reported data, recall bias and small sample size for age categories and gender all present limitations to this study. Increased intakes of refined carbohydrates and red meat consumption could result in higher energy intakes if the components are added to the habitual diets or cause concern if they displace nutrient dense foods as a result of availability of a Western diet. The findings are consistent with the Sanchez et al, 2003 ; who found `Western' and a `Spanish Mediterranean Pattern' and suggested that younger, sedentary, more educated and single male subjects were more likely to give up the traditional Mediterranean pattern in Spain 2 ; . Symi is an island undergoing rapid development and in particular this raises the need for public health nutritionists to ensure the preventative health agenda is promoted which supports choosing healthier options from the Western diet particularly with the younger generation and axid.
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North side of the Crabstane between the croft of John Kintor on the west and the croft of Richard Kyntor on the east, which croft the granter obtained by conquest from William Gift'ard, who on payment to the vicar and chaplains of a sum of 10 merks for the purchase of another annual rent of 6s., should be entitled to free regress to the same; an annual rent of 32d. furth of a land on the west side of the Denburn between the granter's own land on the south and a croft of the Carmelite Friars on the west; an annual rent of 9s. furth of the granter's temple lands on the west side of the Denburn between the croft of the Friars on the west and the common highway leading to Crabstan on the south; and if the tenement last mentioned should become defective or ruinous and not distrainable for the said 9 shillings the granter provides that the same shall be upliftable furth of his croft within the territory of said burgh between the Friars' Croft called the Dowkat Croft on the west and the Denburn on the east; and an annual rent of 12 pennies furth of the land of Alexander Pollaxarn lying on the Denburn above the Bowbrig between the Denburn on and azelaic, for instance, amlodipine atorvastatin.
Extrusion family of efflux proteins found in Pseudomonas aeruginosa, capable of removing multiple structural chemotypes[49-51], and the Qac transporters [52], those proteins capable of removing quaternary ammonium compounds and disinfectants in Staphylococcus [53]. It is clearly evident from the extensive list of efflux pumps, their possible antibiotic substrates, and structural specificities, that the ability to inhibit a broad range of efflux pumps in different bacteria by a single inhibitor will be a daunting task, while designing specific inhibitors of distinct families of efflux pumps is more approachable and currently the focus of our laboratory and others. CHEMICAL DIVERSITY OF EFFLUX SUBSTRATES The compiled list in Table 2 details the transport proteins responsible for efflux, their chemical substrates, both antibiotics and chemical substances, and their transporter family. It appears that the efflux of toxins by bacteria is an universal phenomenon, and includes organic substrates as well as inorganic monovalent and polyvalent cations [54, 55]. Of particular importance are organic cations, exemplified by nitrogenous bases and heterocyclic compounds such as dyes and DNA synthesis inhibitors such as the fluoroquinolones [1, 29]. Other chemically unrelated nitrogenous bases such as ethidium bromide and the quaternary ammonium compounds, particularly those that are effective as antiseptics and detergents, are removed by numerous bacterial hosts as a defense mechanism to.
2003: 473-87. 47. Moosmann B, Behl C. Selenoprotein synthesis and side effects of statins. Lancet 2004; 363: 892-4. Silver MA, Langsjoen PH, Szabo S, et al. Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. Amer J Cardiol 2004; 94: 1306-10. Kumar A, Kaur H, Kumar S, et al. Atorvastatin alone in combination with coenzyme Q10 in 103 cases of heart failure due to ischemic cardiomyopathy. In: Abstract book from the Fourth Conference of the International Coenzyme Q10 Association. Los Angeles 2005: 54-6. 50. Nash DB, Nash SA. Reclassification of simvastatin to overthe-counter status in the United Kingdom: a primary prevention strategy. J Cardiol 2004; 94: 35F-39F. Doggrell SA. New targets and new drugs down under in 2004. Drug News Perspect 2005; 18: 149-60 and azithromycin.
N 1951 cases Mean Baseline CHD risk 8.1 % Composite BioMarker Risk Reduction % Meeting NCEP goal LDL-C Reduction Pravastatin CHD risk 5.4 % 33% 34% 28% Simvastatin CHD risk 5.1 % 37% 58% 36% Atorvastatin CHD risk 5.2 % 36% 76% 42.
It is advised that you carry an identification card that that lets emergency personnel that you are taking this medicine and azulfidine.
Demonstrating correlations of CRP with MI, coronary heart disease, and cardiovascular disease related death. There seems to be a correlation in some of the statin trials A to Z, MIRACL, Prove-It ; between the extent of CRP reduction and early event reduction.9 Much of the early within the first or two years ; benefit of statins appears related to rapid reduction in CRP levels. The greater CRP goes down, or the greater the extent of the anti-inflammatory effects of the drugs, the greater the early event reduction. Statins also appear to have antioxidant effects. LDL needs to be oxidized before it becomes part of atherosclerotic plaques. Statins, particularly atorvastatin, appear to slow down this process of oxidation Exhibit 5 ; .10-12 As atherosclerosis progresses, the plaques can rupture, resulting in acute events, such as MI, unstable angina and stroke. A recently published trial SPARCL ; was specifically designed to examine the effect of a statin on stroke.13 This study included subjects with previously documented stroke or TIA without a history of coronary heart disease. Average LDL levels were between 100 and 160. There was a 16 percent relative risk reduction with statin compared to placebo Exhibit 6 ; .13 This trial demonstrated that history of stroke is an indication for a statin to reduce the risk of having a subsequent stroke. Also in the SPARCL Study, atorvastatin 80 mg substantially decreased the risk of major coronary and vascular events and revascularization procedures. Multiple previous clinical trials have demonstrated the effect of statins on reducing stroke risk in those without coronary heart disease or.
Statines : rhabdomyolyse et myopathie Les statines font partie d'une catgorie d'hypocholestrolmiants qui inhibent l'enzyme hpatique Arductase HMGCoArductase ; . On a tabli un lien entre l'utilisation d'inhibiteurs de la HMGCoA-rductase et une myopathie grave, y compris la rhabdomyolyse16. Les statines dont la vente est approuve au Canada comprennent l'atorvastatine Lipitor ; , la crivastatine Baycol ; , la fluvastatine Lescol ; , la lovastatine Mevacor, Apo-Lovastatin, GenLovastatin ; , la pravastatine Pravachol, Apo-Pravastatin, Bio Pravastatin, Lin-Pravastatin ; et la simvastatine Zocor ; . Le 8 aot 2001, Bayer Inc. a mis fin volontairement la commercialisation et la distribution du Baycol au Canada7, 8. L'examen continu des dclarations postcommercialisation portant sur la rhabdomyolyse, y compris des dcs connexes, a rvl que le taux de dclarations de rhabdomyolyse tait plus lev dans le cas du Baycol que dans celui des autres statines, surtout lorsqu'on prescrit du gemfibrozil simultanment7. BULLETIN CANADIEN EIM janvier 2002; Vol. 12, NO 1 and bactrim.
EZETROL, administered with atorvastatin 40 mg or 80 mg ; or simvastatin 40 mg or 80 mg ; , significantly reduced LDL-C compared with increasing the dose of simvastatin or atorvastatin monotherapy from 40 mg to 80 mg. TABLE 6 Mean Response to EZETROL in Patients with HoFH Mean % Change from Baseline.
Licensed from Ajinomoto Co., Inc. in August, 2006 Anti-diabetic agent with new mechanism Four Phase 1 trials completed in EU and AJD101 was well tolerated and safe for healthy volunteers and patients Phase 2a study is planned in Japan and mechanistic study planned in EU Development exclusively outside Japan, co-development with Ajinomoto in Japan and bromocriptine.
Active ingredient product ; Nefazodone Serzone ; Venlafaxine Effexor ; Current status Withdrawn In the market Year 1999 2000 1999 Cisapride Prepulsid ; Erythromycin Stievamycin ; Withdrawn In the market 1999 2000 1999 Domperidone Cerivastatin Baycol ; Lovastatin Mevacor ; In the market Withdrawn In the market 2002 2003 2000 Pravastatin Pravachol ; In the market 1999 2000 2001 Simvastatin Zocor ; In the market 1999 2000 2001 Fluvastatin Lescol ; Atorvastatin Lipitor ; In the market In the market 1999 2000 Total prescriptions dispensed 526, 459.00 521, Total ADRs 26 16 29 ADRs per 100, 000 prescriptions 4.9 3.1 5.3 Sources: Health Canada, Canadian Adverse Drug Reaction Information System CADRIS ; , 2006; IMS Health Inc. Canada, 2004.
Statins Table 6 ; . In the setting of such elevated RRRs, the usual limitations of SADR data were largely overcome, in part because estimates of the number of statin users were available and in part because the experience of cerivastatin was compared with that of atorvastatin, which had been approved by the FDA at about the same time as cerivastatin Table 3 ; . In contrast to the other statins Table 2 ; , there was no evidence that treatment with cerivastatin prevented coronary heart disease events. Evaluated against a benefit measured only in terms of the surrogate end point of lipid lowering, even the suspicion of serious SADRs such as rhabdomyolysis would plausibly have been sufficient to take action. With 5 other statins on the market, an earlier suspension of cerivastatin sales would not have deprived physicians and patients of effective, sometimes life-saving lipidlowering therapies and cabergoline.
This guidance recognises that whilst switching statins will be appropriate for most people, there will be some patients and their clinicians who prefer not to change medication in this way. Simvastatin 40mg reduces LDL cholesterol slightly more than atorvastatin 10mg and slightly less than atorvastatin 20mg. However, higher HDL is also independently associated with lower CVD events. Simvastatin 40mg results in higher HDL than atorvastatin. Atrovastatin is associated with more `minor' adverse effects than simvastatin. A metaanalysis of trials of atorvastatin 10mg and simvastatin 40mg have shown no significant difference in outcomes, and the one trial comparing atorvastatin 20mg in patients with renal disease ; showed no significant difference. Atrovastatin is now 6 times the price of simvastatin 40mg. Some acute trusts have already adopted a policy of switching atorvastatin or other on-patent statins to simvastatin and this policy is discussed in BMJ Bogle R G, Moon J C BMJ 2006; 332: 1344-5 ; . As there is no substantive advantage of atorvastatin 10 20mg and it is substantially more expensive, it is recommended that.
Accession number & update 16948448 Medline 20061004. Source Soudn lkarstv casopis Sekce soudnho lkarstvi Cs. lkarsk spolecnosti J. Ev. Purkyne Jul 2006, vol. 51, no. 3, p. 47-50, ISSN: 0371-1854. Author s ; Kinoshita-Hiroshi, Fuke-Chiaki, Kubota-Akira, Nishiguchi-Minori, Ouchi-Harumi, Minami-Takako, Matsui-Kiyoshi, Yamamura-Takehiko, Motomura-Hiroyuki, Yoshinaga-Kazumasa, Marukawa-Seishiro, Hishida- Shigeru. Author affiliation Department of Legal Medicine and Emergency, Critical Care and Disaster Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. kinochin hyo-med.ac.jp. Abstract We describe here a case of suicidal poisoning by saponated cresol ingestion. A 41 year-old male was found unconsciousness in a park in the early morning, and an empty bottle of saponated cresol was found beside him. His death was confirmed approximately 2 hours later, despite attempts at resuscitation and intensive care. The autopsy revealed severe morphological damage of the upper gastrointestinal tract and congestion of the lung. We also observed by histopathological examination severe lung edema and severe erosion of the esophagus and stomach. Toxicological analysis also identified a high concentration of cresol isomer in the blood and gastric contents. The cause of death was given as cresol poisoning, based on the results of the autopsy and toxicological examination. Language English. Publication year 2006 and cafergot.
Drug Ergot alkaloids such as dihydroergotamine, ergonovine, ergotamine, methylergonovine Simvastatin, lovastatin, high dose atorvastatin Phenytoin, carbamazepine, phenobarbital Alprazolam, midazolam, triazolam GI motility agents Interaction Impaired hepatic metabolism from PI reported to increase risk of ergotamine toxicity Recommendation Avoid concurrent use with PI therapy. Consider alternative drugs such as sumatriptan. Select pravastatin or low dose atorvastatin during concurrent PI therapy as alternatives. Avoid concurrent use if possible. Consider alternative anticonvulsant during PI therapy. Avoid concurrent use. Consider zolpidem or lorazepam. Contraindicated due to marked increase in cisapride levels and potential for QT prolongation Avoid concurrent use during PI therapy.
TABLE 10 Summary of comparisons, outcomes and results from effectiveness studies cont'd ; Outcome Data RR, 95% CI dichotomous outcomes ; Mean difference, 95% CI continuous outcomes ; RR 1.25 95% CI 0.64 to 2.23 RR 0.87 95% CI 0.5 to 1.59 RR 1.09 95% CI 0.55 to 2.07 and calan and atorvastatin, for example, atorvastatin tablets.
Lead The second most common contaminant found, and on a much less frequent basis, is lead, and 95% of all samples tested had no detectable levels of lead. The average concentration of lead has been 0.005 ppb with 0.6 ppb being the highest concentration detected. This is well below the 1.5 ppb SPAC requirement of NSF 60.
Director, Solid Tumor Service, NewYork-Presbyterian Hospital at NewYork Weill Cornell Medical Center Richard T. Silver Professor of Medicine, Division of Hematology and Medical Oncology, Weill Medical College of Cornell University scw2004 med.cornell and capoten.
Figure 2. Atorvastatin reverts stress fiber formation. The RhoC-expressing A375M cells were plated and treated with DMSO A ; or 3 Atorvastatin B ; for 24 h. Stress fibers are highlighted with arrows.
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Tion of membrane phospholipid acyl chains is a free radical reaction by which molecular oxygen is incorporated into the PUFA moiety following abstraction of a hydrogen atom from the bisallylic methylene group. These chemical modifications alter the structure of the phospholipid molecule, disrupting their physico-chemical interactions with other lipid constituents, such as van der Waals interactions with neighboring phospholipids, especially those containing extended and saturated fatty acyl chains 32 ; . Further studies of cholesterol domain formation in vesicles enriched with other phospholipid molecules, including those containing mixed acyl chains e.g. sphingomyelin ; , are warranted as a function of oxidative stress. In addition to the formation of cholesterol crystalline domains, we observed that oxidative damage to the membrane lipids causes a significant and irreversible reduction in membrane width. This decrease is attributed to chemical modification of the lipid acyl chains, including cleavage into reactive aldehydes. Additionally, as cholesterol was sequestered into these crystalline structures, the overall amount of cholesterol in the surrounding phospholipid bilayer decreased, resulting in increased trans-gauche isomerizations in the phospholipid acyl chains and reduced membrane width. These findings are consistent with previous studies that have demonstrated an important role for cholesterol in maintaining membrane width and lipid dynamics essential for function 2, 33 ; . Such a reduction in membrane width would be expected to have pronounced effects on normal structure-function relationships for membrane-bound ion transport proteins and other proteins involved in signal transduction pathways 33, 34 ; . These findings suggest that the cardiovascular risk factors associated with oxidative stress e.g. hypertension, diabetes ; 7 ; could accelerate the abnormal deposition of cholesterol into crystalline domains, even in patients with normal cholesterol levels in the vessel wall. Levels of oxidized lipid, as measured by TBARS or monoclonal antibodies against oxidized LDL, correlate with the severity of acute coronary syndromes and plaque instability 3537 ; . In a longitudinal investigation of 634 patients, we found that elevated levels of oxidized lipid in the plasma were associated with a 3 4-fold increase in the relative risk for major vascular events and procedures over a 3-year period 37 ; . The predictive effect of TBARS was observed in a multivariate model adjusted for inflammatory markers C-reactive protein, soluble intercellular adhesion molecule-1 sICAM-1 ; , interleukin-6 ; and other risk factors age, LDL, high density lipoprotein, total cholesterol, triglycerides, body mass index, and blood pressure ; . This analysis showed an independent effect of oxidized lipids on major vascular events and procedures. Despite this link between oxidative stress and cardiovascular risk, it has been demonstrated that antioxidant e.g. vitamin E ; supplementation does not appear to be beneficial in reducing events in prospective trials including patients with coronary artery disease 38, 39 ; . Possible explanations for this apparent paradox may be due to trial design, baseline antioxidant status of participants, dosage and source of the antioxidants, and time of intervention relative to disease progression. An additional explanation is that vitamin E does not neutralize relevant oxidants, such as those produced by myeloperoxidase 40 ; , and or that there is reduced penetration of natural antioxidants into the atherosclerotic plaque 41 ; . Our results support the later hypothesis as we observed a reduction in the activity of vitamin E as a function of increasing membrane cholesterol content Fig. 8 ; . By contrast, synthetic antioxidants e.g. probucol ; , with superior scavenging activity and lipophilic properties, may have beneficial effects on relevant oxidative stress processes in the plaque and thereby beneficially influence the course of the disease. The finding of a novel antioxidant effect for ATM may serve to explain why this statin may reduce clinical events in patients with otherwise normal levels of serum LDL, especially in the presence of other risk factors that contribute to oxidative stress pathways e.g. hypertension, diabetes ; , as observed in recent clinical trials, such as the AngloScandinavian Cardiac Outcomes Trial ASCOT ; 18 ; . As reported in the Physicians' Desk Reference 42 ; , 70% of the atorvastatin is present in the serum in the form of hydroxy metabolites that are active inhibitors of HMG-CoA reductase. Unlike other statins, ATM has the same enzymatic activity as its parent. Atorvastatin treatment has been successfully used to reduce the risk and progression of cardiovascular disease 16 18 ; , but there is also clinical evidence that this agent has anti-inflammatory and antioxidant properties that may not be solely related to LDL reduction 1215 ; . A small clinical study that measured protein oxidation markers e.g. dityrosine, nitrotyrosine ; showed that treatment with atorvastatin caused a significant decrease in these oxidation products. Interestingly, reductions in oxidation markers were observed at its lowest dose 10 mg ; over just 12 weeks 15 ; . In larger study of 2341 patients, treatment with a high dose of atorvastatin 80 mg ; caused a significant reduction in levels of oxidized lipids on all apoB-100 particles after just a 16-week period 14 ; . Comparative studies into the effects of atorvastatin versus other statins on biomarkers of oxidative stress are currently underway and will provide additional insight into this potential non-LDL mechanism of action!
You may not be able to take atorvastatin, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.
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