Current pharmaceutical design
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Approximately 10-15% of patients on DOACs have to interrupt their anticoagulant before an invasive procedure every year. The perioperative management and monitoring of DOACs have proved to be challenging, as differences in patients' status and in the invasiveness of each procedure develop different situations that need a tailored therapeutic approach to each patient's needs. ⋯ Further perioperative research studies on patients undergoing vascular surgery are needed to confirm whether currently accepted therapeutic perioperative strategy is appropriate for these patients.
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Drugs mimicking natural beneficial mutations, including that for familial hypercholesterolemia (FH), might represent the future of hypolipidemic drug treatment. ⋯ Mimicking the beneficial naturally happening mutations in lipid metabolism pathways with biological drugs is probably the future of hypolipidemic drug treatment.
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Accumulating evidence has indicated that formation and accumulation of advanced glycation end products (AGEs) progress under diabetic conditions, thereby contributing to the development and progression of various diabetes- and aging-related disorders, such as diabetic nephropathy, diabetic retinopathy, atherosclerotic cardiovascular disease, insulin resistance, cancer growth and metastasis, osteoporosis, and Alzheimer's disease. Modification of proteins, lipids and nucleic acids by AGEs alter their structural integrity and function, and evoke oxidative stress generation and inflammatory reactions through the interaction with a receptor for AGEs (RAGE), being involved in the above-mentioned devastating disorders. ⋯ Since aptamers can be easily generated and highly penetrated into various organs with a low risk of allergic reactions, they may be superior to antibodies for neutralizing and/or blocking target proteins or cell surface receptors. Therefore, in this review, we describe the therapeutic potential of DNA-aptamers raised against the AGE-RAGE axis in diabetes-associated complications, especially focusing on vascular complications of diabetes and cancer.
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Recently, we identified the circadian rhythm protein Period 2 (PER2) in robust cardioprotection from myocardial ischemia (MI). Based on findings that perioperative MI is the most common major cardiovascular complication and that anesthetics can alter the expression of PER2, we hypothesized that an anesthesia mediated downregulation of PER2 could be detrimental if myocardial ischemia and reperfusion (IR) would occur. ⋯ We identified midazolam mediated downregulation of cardiac PER2 as an underlying mechanism for a deleterious effect of midazolam pretreatment in myocardial IR-injury. These findings highlight PER2 as a cardioprotective mechanism and suggest the PER2 enhancers nobiletin or tangeritin as a preventative therapy for myocardial IR-injury in the perioperative setting where midazolam pretreatment occurs frequently.
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Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women during the reproductive period. True PCOS phenotype is prone to develop metabolic consequences during life. Obese PCOS women with insulin resistance are carrying a risk for developing type 2 diabetes, and influencing liver function by generating liver steatosis and nonalcoholic fatty liver disease (NAFLD). ⋯ Metformin remains the drug of choice for reduction of insulin resistance and liver enzymes level. Liraglutide, glucagon-like peptide-1 receptor agonists, showed favorable effects on the reduction of liver fat content and visceral adipose tissue in overweight women with PCOS. Current review analyzes the impact of metabolic risk factors, diagnostic approach and management options on NAFLD in women with PCOS.