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EN
Purpose: Hyperglycemia and increased concentrations of elastin degradation products (EDPs) are common findings in patients with diabetes, atherosclerosis and hypertension. The aim of this study was to assess the influence of high glucose, EDPs and atorvastatin on MMP-1, MMP-2, MMP-9 and TIMP1-3 gene expression in human retinal pigment epithelial cells (HRPE) in vitro. Method: HRPE were cultured for 24 hours with the substances being tested (glucose, EDPs), alone or in combination. Additionally, the cells were treated with atorvastatin in two different concentrations (1 or 10 μM). After incubation, total cellular RNA was extracted and used for gene expression evaluation. Gene expression was measured using the real-time RT-PCR technique. Results: Glucose, EDPs and atorvastatin had no impact on TIMP-1 and TIMP-3 expression. HRPE cells treated with glucose or EDPs with the addition of atorvastatin had a statistically significant decrease of TIMP-2 expression; glucose alone decreased MMP-1 expression. Atorvastatin decreased expression of all assessed genes, except TIMP-1 and TIMP-3 in a dose-dependent manner. Conclusions: Our results confirm the importance of MMPs and TIMPs in retinal vascular biology. Atorvastatin-induced MMPs gene expression can deeply affect extracellular matrix turnover, which may play an important role in the progression of ocular diseases.
EN
A simple and sensitive liquid chromatography—tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C18 Analytical, 4.6 × 100 mm (3.5 μm) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 μL min−1. The column was kept at constant temperature (25 °C), and autosampler tray temperature was set at 4 °C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 → Q3, collision energy) atorvastatin (559.47 → 440.03, 22 eV), atorvastatin lactone (541.36 → 448.02, 19 eV), ortho-ohydroxyatorvastatin (575.20 → 440.18, 20 eV), para-hydroxyatorvastatin (575.54 → 440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5–20 ng mL−1 for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1–20 ng mL−1 for atorvastatin and atorvastatin lactone with excellent linearity (r2 ≥ 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL−1 for orth-ohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL−1 for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.
EN
Myeloperoxidase (MPO) and C-reactive protein (CRP) may play critical roles in generation of oxidative stress and the development of the systemic inflammatory response. The aim of the study was to determine the effect of atorvastatin therapy on the MPO gene expression and its plasma level in relation to lipids level lowering and an anti-inflammatory response in patients after acute myocardial infarction. The research material was represented by 112 samples. Thirty-eight patients with first AMI receiving atorvastatin therapy (40 mg/day) and followed up for one month were involved in the study. The relative MPO gene expression in peripheral blood mononuclear cells (PBMCs) was examined using RT-qPCR in 38 patients before-, 38 patients after-therapy and in 36 patients as the control group. The plasma concentrations of MPO and serum concentrations of biochemical parameters were determined using commercially available diagnostic tests. After one month of atorvastatin therapy, in 60.5% patients a decrease of MPO gene expression, whereas in 39.5% patients an increase, was observed. The plasma MPO levels behaved in the same way as the MPO gene expression. However, the serum lipids and CRP concentrations were significantly lower after one month of atorvastatin therapy in both groups of patients - with decreased and increased MPO gene expression. Atorvastatin exhibited a different effect on MPO gene expression and its plasma level. Short-term atorvastatin therapy resulted in lipid lowering and anti-inflammatory activity in patients after AMI, independently of its effect on MPO gene expression. The molecular mechanisms of this phenomenon are not yet defined and require further research.
EN
This article describes a new, simple, precise and accurate TLC method for simultaneous quantitation of atorvastatin (ATO), ezetimibe (EZE), and fenofibrate (FEN) as the bulk drug and in tablet dosage forms. Chromatographic separation of the drugs was performed on aluminum plates precoated with silica gel 60 F254 as the stationary phase and the solvent system consisting of chloroform-toluene-methanol-acetic acid 6:3:0.5:0.15 (υ/υ/υ/υ). Densitometric evaluation of the separated zones was performed at 263 nm. The drugs were satisfactorily resolved with RF values of 0.16 ± 0.02, 0.22 ± 0.02, and 0.76 ± 0.02 for ATO, EZE, and FEN, respectively. The accuracy and reliability of the method was assessed by evaluation of linearity (75–375 ng per spot for ATO, 99–594 ng per spot for EZE, and 66–330 ng per spot for FEN), precision intra-day and inter-day RSD values were always less than 1.51 for the titled drugs, accuracy (99.72 ± 0.75% for ATO, 101.25 ± 0.91% for EZE, and 101.06 ± 0.60% for FEN), and specificity, in accordance with ICH guidelines.
EN
A simple and sensitive liquid chromatography-mass spectrometric (LC-MS) method has been developed and validated for the simultaneous determination of ezetimibe (EZE), atorvastatin calcium (ATO), and simvastatin (SMV) in combined dosage forms and human plasma. Successful separation of the studied drugs was achieved on a Zorbax Eclipse Plus C18 column (3.0 × 150 mm, 5 µm) using a mobile phase consisting of acetonitrile and 0.1% formic acid in water (65:35, v/v) at a flow rate of 0.5 mL min-1. Total run time was 9.3 min and diclofenac sodium was used as internal standard (IS). Positive selected ion monitoring (SIM) mode was applied where, the monitored ions were those at m/z values of 392.1, 559.3, 296.0, and 441.4 corresponding to EZE, ATO, IS, and SMV, respectively. The method was fully validated according to the ICH guidelines. The intraday and interday precision showed relative SD values not more than 1.77 and 1.99%; respectively. The limits of detection (LOD) were 0.25, 0.25, and 0.75 ng mL-1 while the limits of quantification (LOQ) were 1.25, 0.75, and 2.5 ng mL-1 for EZE, ATO, and SMV, respectively. The developed method was applied on two types of combined tablets concerning drug assay with mean percent recoveries within acceptable range. The method has been extended to the determination of the studied drugs in human plasma where, a solid phase extraction method was optimized for their extraction with percent recovery not less than 97%.
EN
Cardiovascular (CV) diseases are still the leading cause of death in Poland. In treatment of hypercholesterolemia, HMG-CoA reductase inhibitors (statins) are the first-line drugs with proven beneficial effect on patient prognosis. These drugs include one of the two potent statins, atorvastatin. If the target level of LDL cholesterol is not achieved despite lifestyle changes and statin therapy, a drug with a different mechanism of action, e.g. ezetimibe, is added to the treatment. In this way a greater hypolipemic effect is achieved. Single pill combinations (SPC) containing two active substances in one tablet are a good choice. Indications for therapy with SPC preparations with statins and ezetimibe include therapy for primary hypercholesterolemia, mixed hyperlipidemia, heterozygous and homozygous familial hypercholesterolemia, and prevention of CV events in patients at increased risk for these incidents. SPC drug is used to control hypercholesterolemia with atorvastatin and ezetimibe as separate formulations, at the same doses as in the combination formulation. SPC formulations containing 10 mg of ezetimibe in combination with 10 or, 20, or 40 or 80 mg of atorvastatin are available on the Polish pharmaceutical market.
EN
A good therapeutic option in hypercholesterolemia is the use of combination preparations containing an HMG-CoA reductase inhibitor, such as atorvastatin, and a drug that selectively inhibits the absorption of holesterol and plant sterol derivatives from the gut - ezetimibe - in a single tablet. Such treatment can be implemented in adults with primary hypercholesterolemia, familial hypercholesterolemia or mixed hyperlipidemia, which is already controlled with atorvastatin and ezetimibe as separate preparations, at the same doses as in the combination preparation. The preparation is administered 1x /day at any time, day. It is mostly a safe drug and well tolerated by patients. Possible side effects are mainly due to possible side effects of statins.
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EN
In an in uitro experiment the effect of three statins (atorvastatin [Sortis], simvastatin [Zocor], fluvastatin [Lescol]) on the growth of 5 bacterial strains Bacillus subtilis, Bacillus cereus, Proteus vulgaris, Pseudomonas fluorescens, Escherichia coli and 4 saprophytic actinomycetes Streptomyces longisporoflavus, Streptomyces intermedius, Streptomyces odoriver, Streptomyces viridis was tested. The experiments were carried out on solidified substrata with microorganisms covered with filter paper rings soaked with aqueous solution of every tested statin used in different concentrations. It was found that examined substances can inhibit the growth of certain saprophytic microorganisms. Fluvastatin rather than simvastatin or atorvastatin produces stronger effect on bacteria and actinomycetes.
PL
W doświadczeniu in vitro badano wpływ trzech statyn (atorwastatyny [Sortis], simwastatyny [Zocor], fluwastatyny [Lescol]) na rozwój 5 szczepów bakterii: Bacillus subtilis, Bacillus cereus, Proteus vulgaris, Pseudomonas fluorescens, Escherichia coli oraz 4 saprofitycznych promieniowców: Streptomyces longisporoflavus, Streptomyces intermedius, Streptomyces odoriver, Streptomyces viridis. Doświadczenia prowadzono na zestalonych podłożach, przy czym mikroorganizmy przykrywano krążkami papieru filtrującego, nasączonymi wodnym roztworem poszczególnych statyn w różnych stężeniach. Stwierdzono, że badane substancje mogą ograniczać rozwój pewnych mikroorganizmów saprofitycznych. Fluwastatyna miała silniejszy wpływ hamujący na bakterie i promienowce niż simwastatyna lub atorwastatyna.
EN
This year, the European Society of Cardiology (ESC) has published new guidelines on the diagnosis and management of arterial hypertension, management of patients with stable coronary artery disease and guidelines on approach to cardiovascular disease in patients with diabetes and pre-diabetes. The incidence of all of these disorders in the general population is very high. In everyday clinical practice, physicians, regardless their specialties, very often face patients with arterial hypertension, diabetes or coronary artery disease. To treat patients in accordance with the latest recommendations, clinicians must constantly learn and expand their knowledge. In the context of the publication of the new guidelines it is particularly important to familiarize yourself with the newly introduced rules on pharmacotherapy in relation to newest findings published in recent years. In this field changes are the most dynamic and with a very high degree of influence on the treatment of patients. Some of pharmaceutical groups used in cardiology are gaining importance, others are slowly being replaced. Position of drug classes such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins or aspirin in the treatment and prevention of cardiovascular events, in the current guidelines has been strengthened. However, in the case of these classes of drugs very important is the choice of specific substance, which will meet the expectations of both the effectiveness and safety in therapy. Present paper, in addition to summarizing the ESC most recent guidelines, demonstrates scientific evidence for the clinical efficacy of substances such as ramipril, telmisartan, atorvastatin or rosuvastatin in patients with diseases of the cardiovascular system.
PL
W bieżącym roku Europejskie Towarzystwo Kardiologiczne (European Society of Cardiology, ESC) opublikowało nowe wytyczne dotyczące diagnostyki i leczenia nadciśnienia tętniczego, postępowania u chorych ze stabilną chorobą wieńcową oraz wytyczne dotyczące chorób układu sercowo-naczyniowego w grupie pacjentów z cukrzycą. Częstość występowania wszystkich tych schorzeń w populacji ogólnej jest bardzo wysoka. W codziennej praktyce klinicznej lekarze, niezależnie od wykonywanej specjalizacji, bardzo często spotykają się z pacjentami z nadciśnieniem tętniczym, cukrzycą czy chorobą wieńcową. Aby leczyć pacjentów zgodnie z najnowszymi zaleceniami, lekarze praktycy muszą stale pogłębiać swoją wiedzę. W kontekście publikacji nowych wytycznych szczególnie istotne jest zapoznanie się z wprowadzanymi zasadami dotyczącymi farmakoterapii – właśnie w stosunku do leczenia farmakologicznego obserwowane w ostatnich latach zmiany są najbardziej dynamiczne i w bardzo wysokim stopniu wpływają na sposób postępowania z pacjentami. Niektóre ze stosowanych w kardiologii grup farmaceutycznych zyskują na znaczeniu, inne powoli zastępowane są nowymi substancjami. W obecnych wytycznych pozycja inhibitorów konwertazy angiotensyny, blokerów receptora angiotensynowego, statyn oraz kwasu acetylosalicylowego w leczeniu oraz prewencji incydentów sercowo-naczyniowych została umocniona. Jednak w przypadku wymienionych grup leków bardzo istotny jest wybór substancji, która będzie spełniać oczekiwania dotyczące zarówno skuteczności działania, jak i bezpieczeństwa terapii. Poniższa praca, poza podsumowaniem najnowszych wytycznych ESC, pokazuje dowody naukowe potwierdzające skuteczność kliniczną takich substancji, jak ramipril, telmisartan, atorwastatyna czy rosuwastatyna, u pacjentów z chorobami układu sercowo-naczyniowego.
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