Publications by authors named "Peter E Penson"

55 Publications

A Systematic Review of Published Physiologically based Kinetic Models and an Assessment of their Chemical Space Coverage.

Altern Lab Anim 2021 Nov 26:2611929211060264. Epub 2021 Nov 26.

School of Pharmacy and Biomolecular Sciences, 4589Liverpool John Moores University, Liverpool, UK.

Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration-time profile at the target site. Physiologically based kinetic (PBK) models can predict organ-level concentration-time profiles - however, the models are time and resource intensive to generate . Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, that is, to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying the chemicals for which a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information, including species, sex, life-stage, route of administration, software platform used and the availability of model equations, was captured for 7541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1150 unique chemicals associated with these models. This PBK model data set has been made readily accessible, as a Microsoft Excel spreadsheet, providing a valuable resource for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors.
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http://dx.doi.org/10.1177/02611929211060264DOI Listing
November 2021

Extreme cardiovascular risk-do we need a new risk category?

Eur Heart J 2021 Nov 18. Epub 2021 Nov 18.

Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Rzgowska 281/289, Lodz 93-338, Poland.

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http://dx.doi.org/10.1093/eurheartj/ehab771DOI Listing
November 2021

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study.

Rheumatol Int 2021 Nov 10. Epub 2021 Nov 10.

Department of Family Medicine and Public Health, Faculty of Medicine, University of Opole, Opole, Poland.

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold.
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http://dx.doi.org/10.1007/s00296-021-05033-9DOI Listing
November 2021

Clinical Features of Familial Hypercholesterolemia in Children and Adults in EAS-FHSC Regional Center for Rare Diseases in Poland.

J Clin Med 2021 Sep 22;10(19). Epub 2021 Sep 22.

Department of Preventive Cardiology and Lipidology, Chair of Nephrology and Hypertension, Medical University of Lodz, 93-338 Lodz, Poland.

Background: Familial hypercholesterolemia (FH) is a genetic autosomal co-dominant metabolic disorder leading to elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Early development of atherosclerotic cardiovascular disease (ASCVD) is common in affected patients. We aimed to evaluate the characteristics and differences in the diagnosis and therapy of FH children and adults. : All consecutive patients who were diagnosed with FH, both phenotypically and with genetic tests, were included in this analysis. All patients are a part of the European Atherosclerosis Society FH-Study Collaboration (FHSC) regional center for rare diseases at the Polish Mother's Memorial Hospital Research Institute (PMMHRI) in Lodz, Poland. : Of 103 patients with FH, there were 16 children (15.5%) at mean age of 9 ± 3 years and 87 adults aged 41 ± 16; 59% were female. Children presented higher mean levels of total cholesterol, LDL-C, and high-density lipoprotein cholesterol (HDL-C) measured at the baseline visit (TC 313 vs. 259 mg/dL (8.0 vs. 6.6 mmol/L), = 0.04; LDL 247 vs. 192 mg/dL (6.3 vs. 4.9 mmol/L), = 0.02, HDL 53 vs. 48 mg/dL (1.3 vs. 1.2 mmol/L), = 0.009). Overall, 70% of adult patients and 56% of children were prescribed statins (rosuvastatin or atorvastatin) on admission. Combination therapy (dual or triple) was administered for 24% of adult patients. Furthermore, 13.6% of adult patients and 19% of children reported side effects of statin therapy; most of them complained of muscle pain. Only 50% of adult patients on combination therapy achieved their treatment goals. None of children achieved the treatment goal.

Conclusions: Despite a younger age of FH diagnosis, children presented with higher mean levels of LDL-C than adults. There are still urgent unmet needs concerning effective lipid-lowering therapy in FH patients, especially the need for greater use of combination therapy, which may allow LDL-C targets to be met in most of the patients.
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http://dx.doi.org/10.3390/jcm10194302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509252PMC
September 2021

The interaction of Helicobacter pylori with cancer immunomodulatory stromal cells: New insight into gastric cancer pathogenesis.

Semin Cancer Biol 2021 Sep 29. Epub 2021 Sep 29.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, The University of Western Australia, Perth, Australia; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Gastric cancer is the fourth most common cause of cancer-linked deaths in the world. Gastric tumor cells have biological characteristics such as rapid proliferation, high invasiveness, and drug resistance, which result in recurrence and poor survival. Helicobacter pylori (H. pylori) has been proposed as a first-class carcinogen for gastric cancer according to the 1994 world health organization (WHO) classification. One of the important mechanisms by which H. pylori affects the gastric environment and promotes carcinogenesis is triggering inflammation. H. pylori induces an inflammatory response and a plethora of different signal transduction processes, leading to gastric mucosal disturbance, chronic gastritis, and a multi-step complex pathway that initiates carcinogenesis. It seems undeniable that the interaction between various cell types, including immune cells, gastric epithelium, glands, and stem cells, is vital for the progression and development of carcinogenesis concerning H. pylori. The interactions of H. pylori with surrounding cells play a key role in cancer progression. In this review, we discuss the interplay between H. pylori and tumor-supportive cells, including mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid derived-suppressor cells (MDSCs) in gastric cancer. It is hoped that clarifying the specific mechanisms for 'cross-talk' between H. pylori and these cells will provide promising strategies for developing new treatments.
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http://dx.doi.org/10.1016/j.semcancer.2021.09.014DOI Listing
September 2021

Nutraceuticals for the Control of Dyslipidaemias in Clinical Practice.

Nutrients 2021 Aug 25;13(9). Epub 2021 Aug 25.

Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Rzgowska 281/289, 93-338 Lodz, Poland.

Dyslipidaemias result in the deposition of cholesterol and lipids in the walls of blood vessels, chronic inflammation and the formation of atherosclerotic plaques, which impede blood flow and (when they rupture) result in acute ischaemic episodes. Whilst recent years have seen enormous success in the reduction of cardiovascular risk using conventional pharmaceuticals, there is increasing interest amongst patients and practitioners in the use of nutraceuticals to combat dyslipidaemias and inflammation in cardiovascular disease. Nutraceutical is a portmanteau term: 'ceutical' indicate pharmaceutical-grade preparations, and 'nutra' indicates that the products contain nutrients from food. Until relatively recently, little high-quality evidence relating to the safety and efficacy of nutraceuticals has been available to prescribers and policymakers. However, as a result of recent randomised-controlled trials, cohort studies and meta-analyses, this situation is changing, and nutraceuticals are now recommended in several mainstream guidelines relating to dyslipidaemias and atherosclerosis. This article will summarise recent clinical-practice guidance relating to the use of nutraceuticals in this context and the evidence which underlies them. Particular attention is given to position papers and recommendations from the International Lipid Expert Panel (ILEP), which has produced several practical and helpful recommendations in this field.
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http://dx.doi.org/10.3390/nu13092957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467462PMC
August 2021

Challenges and Opportunities on Lipid Metabolism Disorders Diagnosis and Therapy: Novel Insights and Future Perspective.

Metabolites 2021 Sep 9;11(9). Epub 2021 Sep 9.

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, 90133 Palermo, Italy.

Dyslipidemia has been globally recognized, for almost seven decades, as one of the most important risk factors for the development and complications of atherosclerotic cardiovascular disease (ASCVD) [...].
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http://dx.doi.org/10.3390/metabo11090611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469479PMC
September 2021

Bacterial lipopolysaccharide-Stoking the fire of residual risk?

Trends Cardiovasc Med 2021 Sep 21. Epub 2021 Sep 21.

School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK.

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http://dx.doi.org/10.1016/j.tcm.2021.09.006DOI Listing
September 2021

Statins as anti-pyroptotic agents.

Arch Med Sci 2021 9;17(5):1414-1417. Epub 2021 Aug 9.

Applied Biomedical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: Pyroptosis is a regulated form of cell death, which is often a consequence of the activation of inflammatory caspases.

Methods: Appropriate inflammatory responses and the induction of pyroptosis enhance the clearance of pathogens and increase innate immunity.

Results: However, excessive pyroptosis contributes to a hyperinflammatory response and aggravates tissue damage, thereby causing inflammatory diseases. There have been recent reports on the modulation of pyroptosis by statins, which may explain part of the pleiotropic actions of these drugs in inflammatory diseases and cancer.

Conclusions: Herein, the extant evidence for the potential value of statins in targeting pyroptosis in various diseases is reviewed.
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http://dx.doi.org/10.5114/aoms/141155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425236PMC
August 2021

RNA Silencing in the Management of Dyslipidemias.

Curr Atheroscler Rep 2021 09 1;23(11):69. Epub 2021 Sep 1.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.

Purpose Of Review: Remarkable reductions in cardiovascular morbidity and mortality have been achieved in recent decades through the widespread use of 'small-molecule' hypolipidaemic drugs such as statins and ezetimibe. An alternative approach is to perturb the production of proteins through ribonucleic acid (RNA) silencing, leading to long-lasting knock-down of specific biological molecules. This review describes the scientific basis of RNA silencing, and critically evaluates the evidence relating to inclisiran, a small interfering RNA against proprotein convertase subtilisin kexin 9 (PCSK9).

Recent Findings: Pooled analysis of three recent ORION trials has demonstrated that twice-yearly administration of inclisiran reduces LDL-C by 50% in a range of patient groups, with only mild adverse effects. Inclisiran provides safe, effective and long-lasting reductions in PCSK9 and LDL-C. The results of the phase-3 ORION-4 outcomes study are eagerly awaited. Further promising RNA silencing technologies have the potential to improve the management of dyslipidaemia.
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http://dx.doi.org/10.1007/s11883-021-00968-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410691PMC
September 2021

Risk-factors associated with extremely high cardiovascular risk of mid- and long-term mortality following myocardial infarction: Analysis of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) registry.

Atherosclerosis 2021 09 13;333:16-23. Epub 2021 Aug 13.

Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. Electronic address:

Background And Aims: Risk-factor identification and risk stratification are prerequisites to the effective primary and secondary prevention of cardiovascular disease (CVD). Patients at the highest risk benefit the most from the intensive risk-factor reduction. However, the high-risk patients' group is heterogeneous, and it is increasingly recognised that there is an 'extreme-risk' category of patients who may require particularly close attention and intensive therapeutic approach. The aim of this study was to identify subgroups of patients at the highest risk of death following myocardial infarction (MI) that might be considered as those at extremely high CVD risk.

Methods: We used data from 19,582 participants of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry (NCT03065543) of patients with ischaemic heart disease in Poland from 2006 to present. Characteristics of 13,052 patients with chronic coronary syndromes (CCS) were compared with those of 4295 patients with myocardial infarction (STEMI and NSTEMI). Multivariable logistic regression with stepwise backward elimination was used to identify risk factors associated with mortality in the 12-36 months following the index hospitalisation.

Results: The mortality rates were significantly higher in patients after MI than in patients with CCS. In the multivariable analysis, the risk factors most strongly associated with 12-month mortality in patients after MI were left ventricular ejection fraction (LVEF) lower than 35% (hazard ratio [HR] 3.83, 95% confidence interval [CI] 3.14-4.67), age >75 years (HR 1.91, 95%CI 1.55-2.35), multivessel coronary artery disease (HR 1.61, 95%CI 1.30-1.99), atrial fibrillation (HR 1.53, 95%CI 1.21-1.94) diabetes mellitus (HR 1.35, 95%CI 1.11-1.64) and increased LDL-C (HR per 1 mmol/l 1.09, 95%CI 1.01-1.19) or creatinine levels (HR per 10 μmol/L 1.04, 95% CI 1.04-1.05). The risk factors that influenced mortality after 24-36 months were consistent with those after 12 months, with additional low haemoglobin (20-25% risk increase per 1 mmol reduction) and chronic obstructive pulmonary disease (65% risk increase after 36 months).

Conclusions: In our large, single-center real-world analysis, we identified the patients with the highest risk of death who could probably benefit the most from the most intensive therapy, and hence should be considered to be an 'extreme risk' population.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.08.024DOI Listing
September 2021

Efficacy and safety of colchicine in patients with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials.

Br J Clin Pharmacol 2021 Aug 18. Epub 2021 Aug 18.

Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Poland.

Aims: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta-analysis was to evaluate the efficacy and safety of colchicine in patients with CAD.

Methods: We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all-cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short-term effect of colchicine on inflammatory markers.

Results: Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta-analysis. At mean follow-up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P < .001), recurrent myocardial infarction (3.41 vs. 4.41%; P = .005), stroke (0.40 vs. 0.90%; P = .002) and hospitalization due to CV events (0.90 vs. 2.87%; P = .02) compared to the control group. The 2 patient groups had similar risk for all-cause mortality (2.08 vs. 1.88%; P = .82) and CV mortality (0.71 vs. 1.01%; P = .38). Colchicine significantly reduced high-sensitivity C-reactive protein (-4.25, P = .001) compared to controls but did not significantly affect interleukin (IL)-β1 and IL-18 levels.

Conclusion: Colchicine reduced CV events and inflammatory markers, high-sensitivity C-reactive protein and IL-6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all-cause mortality requires further investigation.
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http://dx.doi.org/10.1111/bcp.15041DOI Listing
August 2021

Postmarketing nutrivigilance safety profile: a line of dietary food supplements containing red yeast rice for dyslipidemia.

Arch Med Sci 2021 4;17(4):856-863. Epub 2021 Mar 4.

IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.

Introduction: In the absence of a European standardized postmarketing food supplement surveillance system (nutrivigilance), some member states and companies have developed their own approaches to monitoring potential adverse reactions to secure a high level of product safety. This paper describes the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected adverse reactions associated with food supplements containing red yeast rice (RYR).

Material And Methods: We report the data from a widely used product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1 October 2004 to 31 December 2019, this system captured cases of suspected adverse reactions spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality.

Results: The total number of case reports received mentioning the RYR food supplement product line was 542, in which 855 adverse events (AEs) were reported. The total reporting rate of AEs was estimated to be 0.037% of 2,287,449 exposed consumers. Of the 542 cases, 21 (0.0009% of exposed consumers) included suspected serious adverse events (SAEs). After careful investigation, 6 cases (0.0003% of consumers exposed) and 6 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical.

Conclusions: This nutrivigilance-derived data analysis clearly demonstrates a low prevalence of suspected adverse events associated with the red yeast rice product line. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement's labeling.
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http://dx.doi.org/10.5114/aoms/133716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314417PMC
March 2021

Impact of nutraceuticals on markers of systemic inflammation: Potential relevance to cardiovascular diseases - A position paper from the International Lipid Expert Panel (ILEP).

Prog Cardiovasc Dis 2021 Jul-Aug;67:40-52. Epub 2021 Jun 27.

Department of Hypertension, Medical University of Lodz (MUL), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. Electronic address:

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.pcad.2021.06.010DOI Listing
August 2021

Nocebo/drucebo effect in statin-intolerant patients: an attempt at recommendations.

Eur Heart J 2021 Jun 21. Epub 2021 Jun 21.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Rzgowska 281/289, 93-338 Lodz, Poland.

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http://dx.doi.org/10.1093/eurheartj/ehab358DOI Listing
June 2021

Potential benefits of phytochemicals for abdominal aortic aneurysm.

Curr Med Chem 2021 Jun 14. Epub 2021 Jun 14.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Abdominal aortic aneurysms (AAAs) is an important cause of death in older adults due to aortic rupture. There are currently no effective medical therapies for AAA, with surgery being the only acceptable treatment. There is frequently an extended period between AAA diagnosis and treatment by corrective surgery, during which an effective drug therapy could prevent or delay the need for AAA repair.

Objective: The aim of this review was to critically summarize prior research investigating the potential benefits of phytochemicals in preventing or treating AAA.

Methods: In vitro, in vivo and human studies examining the effect of phytochemicals in AAA models and patients were critically summarised.

Results: Some preliminary data support the further investigation of curcumin, radix astragali, grape seed polyphenols, resveratrol, Ginkgo biloba extract (EGb 761), Ginsenoside Rb1, Dan Hong, Epigallocatechin-3-gallate, Baicalein, Fucoidan, Quercetin and Salvianolic acid as potential treatments for AAA.

Conclusion: Experimental in vivo and in vitro studies suggest the potential benefits of a number of medicinal herbs and phytochemicals in preventing or reducing the progression of AAA. In order to assess whether these findings can be translated into proven treatments, will require adequately designed double-blind randomized clinical trials.
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http://dx.doi.org/10.2174/0929867328666210614113116DOI Listing
June 2021

Colchicine and Cardiovascular Outcomes: a Critical Appraisal of Recent Studies.

Curr Atheroscler Rep 2021 05 10;23(7):32. Epub 2021 May 10.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

Purpose Of Review: Recent studies have demonstrated an important role for inflammation in the pathogenesis of atherosclerotic cardiovascular disease. Several studies have investigated the efficacy of colchicine (a widely used and safe anti-inflammatory drug) in patients with atherosclerosis. This review explains the rationale for the use of colchicine in this setting and critically appraises recent outcome trials.

Recent Findings: Two large randomised-controlled trials LoDoCo2 (included patients with chronic coronary syndromes) and COLCOT (acute coronary syndromes) have demonstrated reductions in atherosclerotic cardiovascular events, but not mortality. A smaller study (COPS) found no beneficial effect of colchicine but was probably underpowered. Colchicine is effective at reducing cardiovascular events in chronic and acute coronary syndromes, although reductions in all-cause mortality have not been demonstrated during the period of follow-up in trials to date. Mild gastrointestinal symptoms are the most commonly reported adverse effects, although in well-designed randomised controlled trials these are relatively uncommon.
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http://dx.doi.org/10.1007/s11883-021-00932-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108024PMC
May 2021

The management of asthma in adult patients in the community pharmacy setting: Literature review.

Res Social Adm Pharm 2021 11 16;17(11):1893-1906. Epub 2021 Apr 16.

School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, Liverpool, United Kingdom; Centre of Pharmacy Innovation, Liverpool John Moores University, Liverpool, United Kingdom.

Background: Asthma poses a public health concern, with an estimated 235 million people currently living with the condition globally. The provision of evidence-based, patient-centred services for adult asthma patients in community pharmacy which involves collaboration across the multidisciplinary team could improve their asthma control.

Objectives: A literature review was conducted to examine the evidence of asthma management in community pharmacy setting.

Methods: Five databases were searched to identify relevant articles published before February 2021. Screening of the potential studies was performed to remove articles that did not comply with the inclusion criteria. Relevant data from all included studies was collected using a data extraction form to ensure consistency throughout the review.

Results: Twenty studies were included in the review; all were conducted in community pharmacy settings in the period of 2001-2020, in different countries. The studies included randomised controlled trials, controlled trials and observational studies. Several successful community pharmacy-based services that were provided to asthma patients to improve their asthma management were highlighted in this review. These interventions consisted of one or more components and included: patient education, inhaler technique improvement, patient counselling, self-management plans, development and provision of asthma action plans and referral to other health care practitioners. None of the studies involved medication or dosage changes by community pharmacy.

Conclusions: The evidence discussed in this review showed that community pharmacists are well-placed to deliver services to asthma patients and many studies were conducted in the community pharmacy to improve asthma control in adult patients. However, further research could be conducted to explore further opportunities for community pharmacy to enhance asthma patients management of their condition.
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http://dx.doi.org/10.1016/j.sapharm.2021.04.001DOI Listing
November 2021

Drucebo effect - the challenge we should all definitely face!

Arch Med Sci 2021 12;17(2):542-543. Epub 2021 Jan 12.

Liverpool John Moores University, Liverpool, UK.

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http://dx.doi.org/10.5114/aoms/132304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959055PMC
January 2021

Cellular senescence, telomeres, and cardiovascular risk in familial hypercholesterolaemia.

Eur J Prev Cardiol 2020 Dec 30. Epub 2020 Dec 30.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

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http://dx.doi.org/10.1093/eurjpc/zwaa145DOI Listing
December 2020

Effects of statins on myocarditis: A review of underlying molecular mechanisms.

Prog Cardiovasc Dis 2021 Jul-Aug;67:53-64. Epub 2021 Feb 20.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Myocarditis refers to the clinical and histological characteristics of a diverse range of inflammatory cellular pathophysiological conditions which result in cardiac dysfunction. Myocarditis is a major cause of mortality in individuals less than 40 years of age and accounts for approximately 20% of cardiovascular disease (CVD) events. Myocarditis contributes to dilated cardiomyopathy in 30% of patients and can progress to cardiac arrest, which has a poor prognosis of <40% survival over 10 years. Myocarditis has also been documented after infection with SARS-CoV-2. The most commonly used lipid-lowering therapies, HMG-CoA reductase inhibitors (statins), decrease CVD-related morbidity and mortality. In addition to their lipid-lowering effects, increasing evidence supports the existence of several additional beneficial, 'pleiotropic' effects of statins. Recently, several studies have indicated that statins may attenuate myocarditis. Statins modify the lipid oxidation, inflammation, immunomodulation, and endothelial activity of the pathophysiology and have been recommended as adjuvant treatment. In this review, we focus on the mechanisms of action of statins and their effects on myocarditis, SARS-CoV-2 and CVD.
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http://dx.doi.org/10.1016/j.pcad.2021.02.008DOI Listing
August 2021

Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP).

Pharmacol Res 2021 04 17;166:105499. Epub 2021 Feb 17.

Department of Internal Medicine, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia. Electronic address:

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.
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http://dx.doi.org/10.1016/j.phrs.2021.105499DOI Listing
April 2021

Lipid-lowering therapies: Better together.

Atherosclerosis 2021 03 12;320:86-88. Epub 2021 Jan 12.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK.

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http://dx.doi.org/10.1016/j.atherosclerosis.2021.01.009DOI Listing
March 2021

How much should LDL cholesterol be lowered in secondary prevention? Clinical efficacy and safety in the era of PCSK9 inhibitors.

Prog Cardiovasc Dis 2021 Jul-Aug;67:65-74. Epub 2020 Dec 28.

Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Department of Hypertension, Medical University of Lodz (MUL), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. Electronic address:

There is a strong evidence that more marked lowering of low-density lipoprotein cholesterol (LDL-C) leads to progressively lower risk of cardiovascular disease (CVD) events. The evidence on validity of this hypothesis comes from epidemiological, genetic and clinical studies. The hypothesis "the lower the better" has been recently strongly supported by the results of secondary prevention trials with PCSK9 inhibitors. The combination of PCSK9 inhibitors and statins has resulted in achieving extremely low LDL-C levels with additional reduction of CVD events in secondary prevention. However, despite large clinical benefits, the safety of aggressive LDL-C lowering should be always taken into consideration, and there is still an ongoing discussion on whether very low LDL-C might result in some non-CVD adverse events. However, based on the available knowledge, so far the serious adverse events associated with achieving of very low LDL-C levels or intensive drug therapy have not been noted. These positive clinical effects were reflected in current ESC/EAS Guidelines (2019) for dyslipidaemia management. The experts strongly recommended the LDL-C lowering to levels that have been achieved in trials of PCSK9 inhibitors. In this state of the art review, we aimed to finally justify the critical need for LDL-C reduction to very low levels in secondary prevention patients in order to be as low as possible, as early as possible, and preferably lifelong.
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http://dx.doi.org/10.1016/j.pcad.2020.12.008DOI Listing
October 2021

Recent Advancements in Liposome-Based Strategies for Effective Drug Delivery to the Brain.

Curr Med Chem 2021 ;28(21):4152-4171

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Disorders of the central nervous system (CNS) and tumors of the brain are challenging to treat, and they rank amongst the most common causes of death worldwide. The delivery of drugs to the brain is problematic because the blood-brain barrier (BBB) effectively arrests the transport of large molecules (including drugs) from the blood to the CNS. Nanoparticle (NP)-mediated drug delivery has received much interest as a technique to overcome this difficulty. In particular, liposome NPs are promising candidates to carry and deliver drugs across the BBB and into the CNS. Liposomes are easy to prepare, highly biodegradable, and biocompatible. Liposomes can be easily modified with various ligands to enable efficient and targeted drug delivery. Liposomes can promote increased cellular uptake of drugs and can reduce the extent to which efflux transporters can remove drugs. Liposomes can be loaded with a wide range of drugs and biologically active substances. In this review, we will summarize recent advances in research relating to liposome-based strategies to enable drug delivery across the BBB.
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http://dx.doi.org/10.2174/0929867328666201218121728DOI Listing
July 2021

Natural compounds as anti-atherogenic agents: Clinical evidence for improved cardiovascular outcomes.

Atherosclerosis 2021 01 24;316:58-65. Epub 2020 Nov 24.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. Electronic address:

Atherosclerosis, a chronic progressive inflammatory condition characterized by the formation of lipid-laden lesions in arterial walls, is associated with substantial morbidity (including ischaemic stroke and myocardial infarction) and mortality. Risk factors for atherosclerosis are well understood and can be ameliorated by evidence-based and guideline-directed pharmaceutical agents (e.g. the reduction of circulating concentrations of low-density lipoprotein cholesterol by statins). Additionally, many natural products (usually food derivatives) and 'nutraceuticals' (pharmaceutical formulations prepared from components of foods) have been shown to have favourable effects on risk factors for atherosclerotic cardiovascular disease. This literature review summarises the evidence for anti-atherogenic natural compounds. The article focuses on agents which are discussed in international guidelines and are supported by extensive high-quality randomized-controlled trial (RCT) data. We focus on micronutrients (compounds present in food in small quantities) and nutraceuticals, in particular, phytosterols, polyunsaturated ω-3 fatty acids and red-yeast rice. We conclude that the 'nutraceutical approach' (identify the active ingredients in natural products; produce high-quality products according to Good Manufacturing Practice guidelines; evaluate them in long-term outcomes trials) is the mechanism by which the domains of natural product research and evidence-based medicine can move closer together.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.11.015DOI Listing
January 2021

Statins and LDL-C in Secondary Prevention-So Much Progress, So Far to Go.

JAMA Netw Open 2020 11 2;3(11):e2025675. Epub 2020 Nov 2.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

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http://dx.doi.org/10.1001/jamanetworkopen.2020.25675DOI Listing
November 2020

LDL-C: lower is better for longer-even at low risk.

BMC Med 2020 10 8;18(1):320. Epub 2020 Oct 8.

Department of Hypertension, Medical University of Lodz, Rzgowska 281/289, 93-338, Lodz, Poland.

Background: Low-density lipoprotein cholesterol (LDL-C) causes atherosclerotic disease, as demonstrated in experimental and epidemiological cohorts, randomised controlled trials, and Mendelian randomisation studies.

Main Text: There is considerable inconsistency between existing guidelines as to how to effectively manage patients at low overall risk of cardiovascular disease (CVD) who have persistently elevated levels of LDL-C. We propose a step-by-step practical approach for the management of cardiovascular risks in individuals with low (< 1%) 10-year risk of CVD, and elevated (> 140 mg/dL, 3.6 mmol/L) LDL-C. The strategy proposed is based on the level of adherence to lifestyle interventions (LSI), and in case of non-adherence, stepwise practical management, including lipid-lowering therapy, is recommended to achieve a target LDL-C levels (< 115 mg/dL, 3.0 mmol/L).

Conclusions: Further studies are necessary to answer the questions on the long-term efficacy, safety, and cost-effectiveness of the suggested approach. This is critical, considering the ever-increasing numbers of such low-risk patients seen in clinical practice.
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http://dx.doi.org/10.1186/s12916-020-01792-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545575PMC
October 2020

Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone.

Metabolism 2020 12 23;113:154375. Epub 2020 Sep 23.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.metabol.2020.154375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511211PMC
December 2020

The Role of Nutraceuticals in the Optimization of Lipid-Lowering Therapy in High-Risk Patients with Dyslipidaemia.

Curr Atheroscler Rep 2020 09 18;22(11):67. Epub 2020 Sep 18.

Department of Hypertension, Medical University of Lodz, Rzgowska 281/289, 93-338, Lodz, Poland.

Purpose Of Review: We aimed to summarize recent guidelines, position papers, and high-quality clinical research relating the use of nutraceuticals in the management of individuals at high risk of atherosclerotic cardiovascular disease.

Recent Findings: It is essential that individuals at high risk of cardiovascular disease receive guideline-directed evidence-based therapies to reduce their risk of morbidity and mortality from cardiovascular events. Compared with conventional therapeutics, nutraceuticals have undergone relatively little investigation in randomized controlled trials. Thus, recommendations for nutraceuticals in international guidelines are rare, and nutraceuticals should not be used preferentially in place of statins. Nevertheless, recent position papers from the International Lipid Expert Panel and clinical evidence from studies of triglyceride reduction by polyunsaturated fatty acid administration demonstrate that nutraceuticals do have an important role in optimizing therapy in individuals at high risk of cardiovascular disease. Roles for nutraceuticals include as follows: (1) managing residual risk associated with lipids other than low-density lipoprotein cholesterol (LDL-C); (2) managing non-lipid-mediated residual risk; (3) optimizing LDL-C treatment in statin intolerance; (4) optimizing LCL-C treatment when add-on therapies for statins are not available; (5) as adjuncts to lifestyle for individuals at high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The strength of evidence for each of these applications is variable. In addition to guideline-directed therapeutics, nutraceuticals may have roles in optimizing preventative therapy and targeting residual risk in individuals at high risk of ASCVD. Application of Good Manufacturing Practice and randomized controlled trials when producing and evaluating nutraceuticals will expand the armoury of evidence-based agents for the prevention of ASCVD.
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http://dx.doi.org/10.1007/s11883-020-00887-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501132PMC
September 2020
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