Cardiovascular & Haematological Disorders - Drug Targets - Current Issue

The landscape of severe dyslipidemia treatment is undergoing a remarkable transformation with the advent of angiopoietin-like 3 (ANGPTL3) inhibitors. ANGPTL3, a pivotal regulator of lipoprotein lipase and endothelial lipase, orchestrates the catabolism of triglyceride-rich and high-density lipoproteins, thus playing a critical role in lipid homeostasis. This review article examines the therapeutic potential of ANGPTL3 blockade and its implications for patients with severe dyslipidemias, particularly those unresponsive to traditional lipid-lowering regimens. We delve into the molecular mechanisms by which ANGPTL3 influences lipid metabolism and appraise the clinical utility of emerging therapeutics, such as monoclonal antibodies and antisense oligonucleotides. Moreover, we discuss the impact of ANGPTL3 inhibition on cardiovascular risk factors and project its promising role in reducing cardiovascular morbidity and mortality. The narrative synthesizes data from recent clinical trials, including the efficacy and safety profiles of ANGPTL3 inhibitors, and forecasts the potential of these agents to revolutionize the management of dyslipidemic conditions. The advent of ANGPTL3-targeted therapies signifies a potential breakthrough in the therapeutic armamentarium against complex lipid disorders, heralding a new era of precision medicine in cardiovascular risk mitigation.

Systemic amyloidosis is a rare protein misfolding and deposition condition that causes slow organ failure. Each of the more than 15 exclusive sorts of systemic amyloidosis, which encourage amyloid production and tissue deposition, is introduced by a unique precursor protein. Amyloidosis can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin, and soft tissues. It can either be acquired or hereditary. Insidious and doubtful signs often cause a put-off in diagnosis. In the closing decade, noteworthy progressions have been made in the identity, prediction, and handling of amyloidosis. Shotgun proteomics based on mass spectrometry has revolutionized amyloid typing and enabled the identification of novel amyloid forms. It is critical to correctly identify the precursor protein implicated in amyloidosis because the kind of protein influences the proper treatment strategy. Cardiac amyloidosis is a disorder characterized by the systemic accumulation of amyloid protein in the myocardium's extracellular space, which causes a variety of symptoms. The buildup of amyloid aggregates precipitates myocardial thickening and stiffening, culminating in diastolic dysfunction and, in due course, heart failure. We examine every kind of systemic amyloidosis in this text to offer practitioners beneficial equipment for diagnosing and treating those unusual diseases. This review presents a comprehensive analysis of cardiac amyloidosis and consolidates current methods for screening, diagnosis, evaluation, and treatment alternatives.

Background: Kounis syndrome is defined as a combination of acute coronary syndrome and allergic reactions. Objective: In this review, we aim to describe the etiological, clinical, and diagnostic characteristics of Kounis syndrome. Methods: A literature search using PubMed was conducted for the past 32 years using keywords, resulting in the selection of 761 scientific papers. From these, 217 articles describing 235 clinical cases were selected. Patients under 18 years of age or without a confirmed diagnosis were excluded. Results: Among the 235 patients, type I Kounis syndrome was observed in 49.7%, type II in 27.2%, type III in 5.9%, and a combination of types I and II in 1.0%; in 16.2%, it was not possible to classify the type of Kounis syndrome. The median age was 57 years, and 68.5% of the patients were male. The most common causes were antibiotics (32.3%) and non-steroidal anti-inflammatory drugs (24.3%). The clinical features included chest pain (59.1%), hypotension (74.2%), itching (30.6%), and dyspnea (30.6%). Electrocardiographic monitoring revealed ST-segment elevation in 42.9% and was normal in only 5.5% of patients. Coronary angiography was performed in 80.4% of the patients, revealing unchanged coronary arteries in 50.3% of cases. Сonclusion: Allergic myocardial infarction is a serious complication of drug therapy.

Background: Premature Ovarian Insufficiency (POI) is associated with infertility. Little is known about the potential circulating biomarkers that could be used to predict POI. We have investigated the possible association between white and red blood cells, platelet indices, and eight established single nucleotide polymorphisms (SNPs) associated with POI risk. Methods: 117 women with premature menopause (PM) and 183 healthy women without a history of menopause before age 40 were recruited for this study. The tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS PCR) and allele-specific oligonucleotides- polymerase chain reaction (ASO-PCR) were carried out for genotyping for eight SNPs reported to be associated with POI. Decision tree analysis was applied to test the diagnostic value of hematological parameters to identify the risk of POI. Results: Women with POI had lower neutrophil (NEUT) and white blood cell (WBC), whereas red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) were higher. Platelet (PLT) count was also lower in affected women. Our data also indicated that HGB and HCT count were significantly associated with rs16991615 and rs244715. Mean Platelet volume (MPV) and platelet distribution width (PDW) were associated with rs244715, rs1046089, rs4806660, and rs2303369. The rs16991615 was also associated with RBC count, and rs451417 was associated with NEUTs. The decision tree (DT) model reveals that women with the NEUT count at a cut-off value of less than 2.8 and HCT equal to or more than 38.7% could be identified as high-risk cases for POI. Overall, we found the DT approach had a sensitivity = 85%, specificity = 72%, and accuracy = 74%. Conclusion: The genetic variants involved in POI are associated with changes in reproductive hormone levels and with changes in hematological indices.

Background: Diltiazem hydrochloride is a calcium channel-blocker with a plasma elimination half-life of 4.4 ± 1.3 h and has a narrow absorption window. So, this work aimed to prepare a gastro-retentive floating matrix tablet. Methods: The direct compression method was used to manufacture tablets. 3² factorial design was applied for optimization, taking Hydroxypropyl Methylcellulose K100M (HPMC K 100M) and the amount of sodium bicarbonate as independent factors and cumulative percentage release at 1 h, at 6 h, and at 12 h and floating lag time as dependent variables. Results: The high amount of HPMC K100M and sodium bicarbonate shows good results. The optimized preparation was evaluated for differential scanning calorimetry, in-vivo gastric retention in male albino rabbits, kinetic modeling, and stability study. An in vivo study revealed gastric retention of tablets up to 6 h in healthy male Albino rabbits. The stability study indicated no significant change in the buoyancy and release profiles of the drug. Conclusion: From this study, it can be concluded that the gastro-retentive diltiazem hydrochloride floating matrix tablet was successfully prepared and retained inside the rabbit stomach for up to 6 h and was stable under accelerated stability study.