Hypolipidemic drugs inhibiting the proprotein convertase of subtilisin/kexin type 9 (PCSK9): monoclonal antibodies, antisense oligonucleotides, small interfering ribonucleic acids

Hypolipidemic therapy is one of the essential components for the management of patients with cardiovascular diseases (CVD). In this regard, the main task of modern research is to find new targets for creating additional effective groups of hypolipidemic drugs. In 2003, canadian and french research groups led by N. Seidah and M. Abifadel discovered a new enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9), which later turned out to play an important role in lipid metabolism. The main mechanism of action of PCSK9 is to regulate the density of low-density lipoprotein receptors (LDLR) in the cell membrane of hepatocytes. Increased activity of PCSK9 significantly accelerates the degradation of LDL and leads to an increase in the concentration of atherogenic classes of lipoproteins-low-density lipoproteins (LDL). In contrast, reduced PCSK9 activity is accompanied by a decrease in LDL concentrations and a reduced risk of developing atherosclerosis and CVD. The second of the recently discovered and less studied mechanism of PCSK9 protearogenic action is an increase in inflammatory processes in the atherosclerotic plaque. Given this adverse contribution of PCSK9 to the development and progression of atherosclerosis and CVD, the main task of the researchers was to develop drugs that inhibit THIS enzyme. To date, several new groups of drugs have been developed that target the stages of biosynthesis and the function of PCSK9. In this article, we will focus in detail on discussing the mechanisms of action and effectiveness of the following groups of hypolipidemic drugs: anti-PCSK9 monoclonal antibodies (alirocumab, evolocumab), small interfering ribonucleic acids (incliciran), and antisense nucleotides.

Efek Antioksidan pada Teh Hijau terhadap Kadar Kolesterol Darah

Hypercholesterolemia, a condition when blood cholesterol levels exceed the normal value can lead to atherosclerosis and furthermore coronary heart disease. For that reason, some treatment actions are needed, one of which is by given hypolipidemic drugs. One of the natural remedies that act as hypolipidemic drugs is green tea. Green tea contains catechins, one of the antioxidant compounds. Catechins, especially epigallocatechin-3-gallate (EGCG), plays an important role in lowering blood cholesterol levels. The aims of this study is to determine the effect of antioxidants in green tea on blood cholesterol levels. This is a literature review study with data retrieved using 3 databases: Pubmed, ClinicalKey and Google Scholar. Using Green Tea OR Teh Hijau, Cholesterol OR Kolesterol, and Antioxidant OR Antioksidan as keywords and limiting the article searching based on inclusion and exclusion criteria, 12 studies was found to be reviewed. From 12 literature reviewed using experimental research methods with human and animal subjects with intervention green tea (extract, EGCG and PPE), all of them showed a significant reduction in blood cholesterol levels after the intervention with green tea. In conclusion, the antioxidants in green tea can reduce cholesterol levels in the blood.Keywords: antioxidant, green tea, EGCG, cholesterol, hypercholesterolemia Abstrak: Kadar kolesterol yang melebihi batas normal atau biasa disebut hiperkolesterolemia dapat menyebabkan pembentukan aterosklerosis bahkan penyakit jantung koroner. Untuk itu diperlukan penanganan, salah satunya dengan pemberian obat hipolipidemia. Salah satu bahan alami yang dapat berperan sebagai hipolipidemia yaitu teh hijau. Teh hijau mengandung senyawa antiosidan yaitu katekin terutama epigallocatechin-3-gallate (EGCG) yang berperan penting dalam menurunkan kadar kolesterol dalam darah. Tujuan penelitian ini untuk mengetahui efek antioksidan pada teh hijau terhadap kadar kolesterol dalam darah. Penelitian ini berbentuk literature review dengan pencarian data menggunakan 3 database yaitu PubMed, ClinicalKey dan Google Scholar. Kata kunci yang digunakan yaitu Green Tea OR Teh Hijau, Cholesterol OR Kolesterol, dan Antioxidant OR Antioksidan. Setelah diseleksi berdasarkan kriteria inklusi dan eksklusi, didapatkan 12 literature yang di review. Dari 12 literature yang di review menggunakan metode penelitian eksperimental dengan subjek penelitian manusia dan hewan yang diberi teh hijau (ekstrak, EGCG dan PPE) semuanya menunjukkan hasil adanya penurunan kadar kolesterol darah yang signifikan setelah diberikan teh hijau. Sebagai simpulan, antioksidan pada teh hijau dapat menurunkan kadar kolesterol dalam darah.Kata Kunci: antioksidan, teh hijau, EGCG, kolesterol, hiperkolesterolemia

Berberine: A Promising Natural Isoquinoline Alkaloid for the Development of Hypolipidemic Drugs

: Berberine, as a representative isoquinoline alkaloid, exhibits significant hypolipidemic activity in both animal models and clinical trials. Recently, a large number of studies on the lipid-lowering mechanism of berberine and studies for improving its hypolipidemic activity have been reported, but for the most part, they have been either incomplete or not comprehensive. In addition, there have been a few specific reviews on the lipid-reducing effect of berberine. In this paper, the physicochemical properties, the lipid-lowering mechanism, and studies of the modification of berberine all are discussed to promote the development of berberine as a lipid-lowering agent. Subsequently, this paper provides some insights into the deficiencies of berberine in the study of lipid-lowering drug, and based on the situation, some proposals are put forward.

Changes in the intestinal microbiota as a risk factor for dyslipidemia, atherosclerosis and the role of probiotics in their prevention

The review presents an analysis of studies on the role of the intestinal microbiota and microbiome in lipid metabolism and the development of dyslipidemia, atherosclerosis and cardiovascular diseases. The role of the intestine as a metabolic organ with a multifactorial strain evolution, involved in lipid metabolism, cholesterol homeostasis and enterohepatic circulation is shown. The influence of microbial imbalance on the development of dyslipidemia and atherosclerosis is considered. Special attention is paid to preventive therapy with hypolipidemic probiotics. It is shown that the use of probiotics with hypolipidemic properties and consisting of a mixture of such strains asLactobacillus plantarumCECT7527, CET7528 and CECT7529, mixtures ofLactobacillus acidophilusLa-5,Bifidobacterium lactisBB-12,Bifidobacterium animalis lactisBB-12 contribute to reducing the level of LDL-C, CCS, TG, are safe and well tolerated, can be used as an adjuvant non-drug therapy in combination with hypolipidemic drugs for dyslipidemia, multifocal atherosclerosis.

EFFECTIVENESS OF INTRODUCING INTEGRATED ONLINE LEARNING MODULES AMONG PHASE 2 MBBS STUDENTS

Introduction: Online learning has gained acceptance following the implementation of Competency based medical Education (CBME). CBME stresses on integrated learning also which helps in simplifying concepts. Methods: Four topics suitable for integration with Biochemistry and Pharmacology were covered as both lectures and online learning modules among 69 Phase 2 MBBS students after dividing them into two groups. Results and Discussion: The mean±SD of the marks obtained after covering lectures and online modules of the four topics were found to be different and statistically significant- Topic 1 (Gout) lecture 3.91± 1.44; online module 6.35 ± 0.91, Topic 2 (Hypolipidemic drugs) lecture 3.80± 1.32; online module 6.17± 0.71, Topic 3 (Vit D) lecture 4.22± 1.41; online module 7.73± 1.69, Topic 4 (Iron) lecture 4.25± 1.83; online module 7.82± 1.19. In this study we observed that integrated online learning was an efficient method for undergraduate teaching.

High-rate algal pond for removal of pharmaceutical compounds from urban domestic wastewater under tropical conditions. Case study: Santiago de Cali, Colombia

This study evaluated the capacity of a pilot-scale high-rate algal pond (HRAP) to remove pharmaceutical compounds (PCs) from domestic wastewater in the city of Santiago de Cali, Colombia. The compounds analyzed included antiepileptics, hypolipidemic drugs, tranquilizers and analgesics, and anti-inflammatory drugs. The HRAP operated under a continuous water flow of 0.2 m3d−1 and a 3-day hydraulic retention time (HRT). Removal efficiencies were high (>70%) for fenofibric acid, ibuprofen, and paracetamol; medium (30–70%) for gabapentin, lamotrigine, fenofibrate, gemfibrozil, diclofenac, ketoprofen, naproxen, and pentoxifylline; and low (<30%) for carbamazepine and its metabolite 10,11-Dihidro-10,11-dihidroxicarbamazepine (CBZ-Diol). The findings herein are similar to other studies, but were obtained with a shorter HRT. These results show that tropical environmental conditions favor photodegradation and contribute to the development of microalgae and the biodegradation process. Twenty microalgae species were identified, with the phylum Chlorophyta as the most abundant, particularly due to its natural introduction. The removal of the PCs also reflected a percentage reduction (>50%) in the ecological hazard posed by most of the compounds, although it is important to note that the hazard from gemfibrozil and ibuprofen remained high even after treatment, indicating the need for complementary treatment.

Medications associated with development of drug-induced depression

More than 60 % of all depressive syndromes are reactive depression, which occurs in response to internal and external influences. One of the variants of reactive depression is drug-induced (drug-induced) or iatrogenic depression, which is a possible side effect of a number of medications. Depressogenic effect is described in both psychotropic and somatotropic drugs. Depressions that occur when using psychotropic drugs are most often associated with the duration of administration and large doses of the drug. Some antihypertensive, antiarrhythmic, hypolipidemic drugs, antibiotics, hormones, antiparkinsonian drugs and antineoplastic agents are most often mentioned in the series of somatotropic drugs that have a depressogenic effect. Drug-induced depression is one of the most controversial issues. this article presents a systematization of available literature data on depression associated with taking various drugs.