Spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of Curcuma aromatica.

Curcuma aromatica is used as a traditional Chinese medicine, and it is mainly distributed in Guangxi, China. In this study, 10 batches of C. aromatica were collected from different origins in Guangxi. The fingerprints were established by HPLC technique to investigate the quality stability of C. aromatica. The spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica was assessed by similarity analysis, gray relational analysis and multiple linear regression analysis. From the results, the similarity values between each batch of C. aromatica and reference fingerprint were >0.880, indicating the good quality stability of the 10 batches of C. aromatica. Twenty common peaks were selected as the fingerprints to evaluate the quality and hypolipidemic effect of C. aromatica. The results of spectrum-effect relationship showed that peaks 10, 18, 13, 15 and 17 in the fingerprints were closely related to hypolipidemic effect. This study successfully established the spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica, which provided methods for quality control and more effectively studies on bioactive compounds of C. aromatica. It could also provide a new simple and effective method for utilizing the fingerprints to optimize the Chinese prescription and develop traditional Chinese medicine.

Variability in Potency Among Commercial Preparations of Berberine.

Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine's safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from 33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.

[Changes of fingerprints with crude and processed cassiae semen in xuezhiling tablets].

OBJECTIVE: To establish an effective and convenient method for HPLC fingerprints of Xuezhiling tablets and new Xuezhiling tablets, and to observe the changes of fingerprint with crude and processed Cassiae Semen in Xuezhiling tablets. METHODS: The HPLC with Agilent TC-C18 (4.6 mm x 250 mm, 5 microm) column was used for the gradient elution of acetonitrile-0.1% phosphoric acid solution, at the flow rate of 1.0 mL/min. Detection wavelength was set at 284 nm and the column temperature was 30 degrees C. RESULTS: Ten batches of Xuezhiling tablets and new Xuezhiling tablets were tested and gained HPLC fingerprint containing 20 common peaks, respectively. CONCLUSION: This method is stable and reliable. The number of common peaks of fingerprint had little change after the crude and processed Cassiae Semen in Xuezhiling tablets interchangeably, but the contents of some components had significant changes.

[The quality standard study on Hugan qingzhi tablets].

OBJECTIVE: To develop a method of quality control for Hugan qingzhi tablets. METHODS: Fructus Crataegi, Rhizoma Alismatis and Radix Notoginseng were identified by TLC. HPLC was used for the determination of ursolic acid in Hugan qingzhi tablets. RESULTS: The chromatographic spots were identified without the interference of negative control. Ursolic acid had a good linearity over the concentration range of 40-200 microg/mL (r = 1.000). The average recoveries was 99.05% with relatively standard deviations of 1.3%. CONCLUSION: This method is reliable, accurate and specific and can be used for the quality control of Hugan qingzhi tablets.

Utility of atherosclerosis imaging in the evaluation of high-density lipoprotein-raising therapies.

Decreased level of high density-lipoprotein cholesterol (HDL-C) is a rigorous predictor for future cardiovascular events. Much effort is being made to develop HDL-C-raising pharmacotherapies in the attempt to avert the pandemic of atherosclerotic disease. Important properties by which HDL-C-raising compounds are effective involve improvement of cholesterol uptake from macrophages in plaque for transport back to the liver, improvement of endothelial function, and anti-inflammatory effects. Vascular imaging can aid in the determination which HDL-C-raising compounds are effective. Ultrasound and MRI have proved suitable for assessment of structural changes of the vessel wall. Ultrasound can also be used or assessment of endothelial function. 18F-fluordeoxyglucose positron emission tomography has opened up the possibility to assess vessel wall inflammation. In this article we discuss these various imaging techniques and how they can assess efficacy as well as provide pathophysiologic information on the mechanism of action of novel HDL-C-raising drugs.

Chemical characterization of a commercial Commiphora wightii resin sample and chemical profiling to assess for authenticity.

The gum resin of Commiphora wightii [(Hook. ex Stocks) Engl.] is an ayurvedic medicine for the treatment of arthritis, inflammation, obesity, lipid disorders, and cardiovascular diseases and is known as guggul. Morphologically, it is not easy to distinguish guggul from closely related gum resins of other plants. Reliability of the commercially available guggul is critical due to the high risk of adulteration. To check authenticity, a commercial guggul sample was investigated for its chemical markers and 17 metabolites were identified, including three new, 20(S),21-epoxy-3-oxocholest-4-ene (1), 8 ß-hydroxy-3,20-dioxopregn-4,6-diene (2), and 5-(13' Z-nonadecenyl)resorcinol (17) from the ethyl acetate soluble part. During the current study, compounds 14- 17 were identified as constituents of Mangifera indica gum, as an adulterant in the commercial guggul sample. This discovery highlighted the common malpractices in the trade of medicinal raw material in the developing world. The structures of the compounds were deduced by the spectroscopic technique and chemical methods, as well as by comparison with the reported data. The structure of 20(S),21-epoxy-3-oxocholest-4-ene (1) was also unambiguously deduced by single-crystal X-ray diffraction technique.

Assessment of the quality of simvastatin capsules from compounding pharmacies.

OBJECTIVE: To validate a method for determining the simvastatin content of compounded capsules, using high performance liquid chromatography. METHODS: Eighteen samples of simvastatin 40 mg capsules from compounding pharmacies in the cities of São Paulo, Guarulhos, São Bernardo do Campo and Campinas, Southeastern Brazil, prescribed for fictitious patients were assessed. The analyses were based on the Brazilian Pharmacopoeia and on the high performance liquid chromatography method, optimized and validated in accordance with national and international standards for identification and quantification tests on compounded capsules. RESULTS: The mean weight of the capsules ranged from 70 mg to 316 mg; four samples presented weight variation outside of the specification. The simvastatin content in the capsules was within the specification in 11 samples. In six, the content ranged from 4% to 87% of the declared quantity, thereby not complying with the content requirements for the active agent. For one sample, no content or uniformity determinations were performed. In the content uniformity test, 15 samples presented indices of less than 85%, with relative standard deviations greater than 6%. Three pharmacies had met the specification in this test. In the dissolution test, eight samples presented unsatisfactory results in the first stage of the test, while the remainder presented inconclusive results. CONCLUSIONS: The method used was shown to be suitable for application to quality control, and it revealed the poor quality of the simvastatin capsules produced by some compounding pharmacies.

Differences between dietary supplement and prescription drug omega-3 fatty acid formulations: a legislative and regulatory perspective.

The medical management of many diseases and conditions can include either restriction or provision of specific essential nutrients. When such nutrients are needed, there are often both prescription and nonprescription products available, as in the case of nicotinic acid or omega-3 fatty acids. Although they may seem to contain similar ingredients, there may be important differences between the prescription and dietary-supplement preparations. The manufacturing of prescription pharmaceutical products is regulated by the US Food and Drug Administration (FDA), which mandates standards for consistency and quality assurance. Dietary supplements are available to consumers under the provisions of the Dietary Supplement Health and Education Act of 1994, for which the FDA has the burden of proving a dietary supplement is harmful rather than requiring the manufacturer prove that the supplement is safe. Consumers and medical professionals should be aware of the important qualitative and quantitative differences between the FDA-approved prescription formulations and dietary supplements, particularly when an essential nutrient is part of the medical management of a disease or condition.

Low-density lipoprotein lowering in type 2 diabetes mellitus: how to know how low to go.

PURPOSE OF REVIEW: Getting low-density lipoprotein to the right level in patients with type 2 diabetes should be relatively easy, given the potent pharmacological therapy that is available and the fact that low-density lipoprotein C is typically normal in these patients. Getting it right means getting the target for therapy right, however. The article examines the criteria that should be used to make this choice. RECENT FINDINGS: In comparing different parameters, three criteria, in particular, need to be taken into account: the on-treatment predictive value of any parameter; the value relative to the population of one parameter compared with another, namely which is more deviant from the norm; and the concurrent level of high-density lipoprotein. The evidence from the low-density lipoprotein-lowering trials indicates that low-density lipoprotein C is not nearly as good as non-high-density lipoprotein C as a guide for the adequacy of low-density lipoprotein lowering, or, better still, apoB, with the apoB/apoA-I ratio being clearly the best of all. SUMMARY: The evidence from the major clinical trials indicates the best single index of the adequacy of low-density lipoprotein lowering is the apoB/apoA-I ratio. Clinical practice should adapt to clinical evidence and, therefore, guidelines should be based on apolipoproteins rather than the conventional cholesterol indices.

The ALLHAT study revisited: do newer data from this trial and others indicate changes in treatment guidelines?

Following a hypertension symposium in Washington, DC, in November 2006, a panel was convened to discuss new data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and to revisit the significance of this trial in the management of hypertension. Based on these data and information from other trials, the expert panel also addressed the questions, "Is it time for a new Joint National Committee report?" and "Should the 2003 hypertension treatment recommendations be updated or are they still valid?" The panel was moderated by Marvin Moser, MD, Clinical Professor of Medicine, Yale University School of Medicine, New Haven, CT. On the panel were Suzanne Oparil, MD, Professor of Medicine at the University of Alabama in Birmingham, and President of the American Society of Hypertension (ASH); William Cushman, MD, Professor of Preventive Medicine and Medicine at the University of Tennessee in Memphis and attending physician at the Washington, DC, VA Medical Center; and Vasilios Papademetriou, MD, Professor of Medicine at Georgetown University in Washington, DC, and attending physician at the Washington, DC, VA Medical Center. This expert panel discussion was supported by Pfizer Inc and each author received an honorarium from Pfizer Inc for time and effort spent participating in the discussion and reviewing the transcript for important intellectual content prior to publication. The authors maintained full control of the discussion and the resulting content of this article; Pfizer had no input in the choice of topic, speakers, or content.

Should standard medical therapy for angina include a statin?

Although a wealth of evidence supports the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with clinically evident coronary artery disease, these agents are still underutilized. Statins are the most effective agents in reducing low-density lipoprotein-cholesterol among lipid-lowering drugs, and studies have recently shown that they improve endothelial function and plaque stabilization, and induce regression of atherosclerotic lesions. This article reviews the most recent evidence and guideline recommendations supporting the use of statins in chronic stable angina pectoris and acute coronary syndromes.

Dyslipidemia in patients with angiographically confirmed coronary artery disease--an opportunity for improvement.

BACKGROUND: There are few data about lipid profiles in unselected patients with angiographically confirmed coronary artery disease (CAD). HYPOTHESIS: The study was undertaken to investigate the demographics, clinical characteristics, angiographic findings, and baseline lipid status of 1,000 consecutive unselected patients with angiographically confirmed CAD. METHODS: Between April 2001 and July 2002, we obtained informed consent and prospectively collected clinical characteristics, fasting lipid profiles, and angiographic results from 1,000 sequential patients with CAD confirmed by angiography. RESULTS: In these patients with confirmed CAD, 78% had history of hyperlipidemia. Although 62% were receiving lipid-lowering therapy, only 46% had a low-density lipoprotein target of < 100 mg/dl, and only 20% had achieved all four National Cholesterol Education Program-recommended lipid targets. CONCLUSIONS: Better strategies to ensure optimal lipid levels are required. One such method using computerized workflow is being evaluated in this population.

Achieving lipid goals in Europe: how large is the treatment gap?

Despite the established benefits of decreasing low-density lipoprotein cholesterol levels in reducing morbidity and mortality from coronary heart disease, not all patients who would benefit from lipid-lowering therapy are being managed appropriately. An in-depth review of the literature (2000-2003) demonstrates that the 'treatment gap' varies across different clinical settings. Although the use of lipid-lowering agents has increased in recent years, there continues to be a widespread failure in the achievement of recommended lipid levels. A combination of the use of the most efficacious statins, together with intervention strategies to ensure that all eligible individuals receive appropriate treatment to achieve lipid goals, are important considerations in minimizing the burden of dyslipidemia in Europe.

Managing dyslipidemia: putting the new guidelines to work.

A nine-step process can be used to identify and manage patients with dyslipidemias, and clinicians can then fine-tune lipid-lowering interventions as needed. In helping patients reach lipid goals, pharmacists play important roles as both clinical managers and coaches. Multidisciplinary models of care in physician offices and hospitals provide pharmacists with important opportunities to apply their unique knowledge and indirectly obtain reimbursement for professional services.

[Great discrepancies between European, Dutch and Belgian criteria for the use of statins in the prevention of primary cardiovascular disease in family practice]. / Grote discrepanties tussen Europese, Nederlandse en Belgische criteria voor primaire cardiovasculaire preventie met statinen in de huisartsenpraktijk.

OBJECTIVE: To determine the differences in prescribing advice for statines in primary cardiovascular prevention, applying different protocols, in a first-line setting. METHOD: In February-March 2000, at the general practice 'Medicine for the People' in Deurne-Antwerp, Belgium, all contacts with patients known with at least one cardiovascular risk factor and no signs of cardiovascular disease were included in the study. The absolute risk of developing cardiovascular disease in the next 10 years was calculated per patient according to the protocols of the 'European Society of Cardiology' (ESC) and the Dutch College of General Practitioners (NHG) and it was determined whether these protocols advised prescription of statines. It was also determined if the Belgian criteria for repayment of statines, developed by the Rijksinstituut voor Ziekte- en Invaliditeitsverzekering (RIZIV) were met. RESULTS: The study group comprised 143 patients with a mean age of 66 years, of which 51 (36%) were men. According to the RIZIV criteria 75 (52%) patients of these 143 were eligible for the repayment of statines. The NHG protocol advised to prescribe statines for 4 (3%) patients and the ESC protocol for 69 (48%) patients. Of the 75 patients who were considered for repayment, 34 (45%) according to the ESC protocol and 74 (99%) according to the NHG protocol did not need statines. Also, in the whole study population, 28 (20%) patients needed statines according to ESC and 3 (2%) patients according to NHG, but they could not get repayment for statines according to the RIZIV. The ESC protocol estimated the risk per patient on average 8.5% (95% confidence interval: 7.1-9.8; p < 0.0001) higher than the NHG protocol. CONCLUSION: The NHG protocol estimated the risk significantly and markedly lower than the European protocol, although they are both based on the same Framingham data. There also existed a weak concordance between both protocols. The RIZIV criteria were not 'evidence-based'. They incited to an irrational and wasting prescribing behaviour. There is a need for an integrated guideline for primary cardiovascular prevention and for the adjustment of the RIZIV criteria.

Simvastatin in non-insulin-dependent diabetes mellitus: effect on serum lipids, lipoproteins and haemostatic measures.

The clinical efficacy of the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase inhibitor simvastatin in the treatment of hypercholesterolaemia in non-insulin-dependent diabetes (NIDDM), was examined in a double-blind placebo-controlled study of 6 months in 70 patients with NIDDM (age 25-70 years), of whom 57 were randomised to placebo (29 patients) or simvastatin for 6 months, following a 3-month run-in on diet. Patients were hypercholesterolaemic (7.8 (7.6-8.0) (mean (95% confidence intervals)) mmol/l simvastatin vs. 8.0 (7.7-8.5) mmol/l placebo) and mildly hypertriglyceridaemic (2.6 (2.2-3.0) simvastatin vs. 2.9 (2.3-3.5) placebo). Other lipid measures and estimates of glycaemic control and haemostasis were similar in both groups. There were no significant changes in lipids, haemostatic factors, or measures of glycaemic control in the placebo treatment group. Conversely by the end of 24 weeks, simvastatin produced a 28% reduction in cholesterol (to 5.6 (5.0-6.2) mmol/l (P < 0.001)), a 38% reduction in LDL cholesterol (from 5.5 (5.4-5.6) mmol/l to 3.4 (2.8-4.0) mmol/l, P < 0.001), a 15% reduction in triglyceride (to 2.2 (1.8-2.6) mmol/l, P < 0.05, and a 9% rise in HDL (from 1.16 (1.07-1.25) to 1.23 (1.14-1.32) mmol/l, P < 0.05). Improvements in apolipoprotein B (apo B) (-28%, P < 0.001), the LDL cholesterol to apo B ratio (-20%, P < 0.001), and apo A1 (+15%, P < 0.001) were recorded. There were no effects upon fibrinogen, factor VII activity, factor VIII activity, or measures of glycaemic control (fasting glucose, insulin, C-peptide, or HbA1).(ABSTRACT TRUNCATED AT 250 WORDS)