Current Pharmaceutical Design - Volume 28, Issue 10, 2022

Venous thromboembolism (VTE) is a serious complication after major orthopaedic operations, such as a total hip (THA) and knee (TKA) arthroplasty. Therefore, perioperative VTE prophylaxis is recommended; a multitude of modern options are available, including both pharmacologic (aspirin, unfractionated and lowmolecular- weight heparin, vitamin K antagonists, and novel oral anticoagulants) and/or mechanical interventions (early mobilization, graduated compression stockings, intermittent pneumatic compression devices, and venous foot pumps). However, because of the abundance of these possibilities, it is crucial to understand the benefits and drawbacks of each VTE prophylaxis option to ensure that the optimal treatment plan is developed for each patient. The American College of Chest Physicians (AACP) and the American Academy of Orthopaedic Surgeons (AAOS) have both published individual guidelines on VTE prophylaxis regimens, alongside numerous studies evaluating the efficacy and outcomes of the different prophylaxis modalities. The purpose of this review is to provide a summary of the evidence on VTE prophylaxis after elective total hip and knee arthroplasty based on current guidelines and highlight the major concerns and potential complications.

The annual occurrence of venous thromboembolism (VTE) is 300,000-600,000 cases in the United States and 700,000 in Europe. VTE includes deep venous thrombosis (DVT) of upper or lower extremities, superior and inferior vena cava thrombosis, and pulmonary embolism (PE) as well. The primary treatment of DVT includes oral anticoagulation to prevent the progression of the thrombus and decrease the risk of pulmonary embolism. Depending on the symptoms, more invasive treatments can be applied to target the iliofemoral thrombus and its removal. However, less emphasis is given to acute symptomatology, early recovery of function, quality of life improvement, and the individualized likelihood of developing post-thrombotic syndrome. While invasive therapy has been used to enhance the acute management of iliofemoral DVT, our knowledge about the overall outcomes associated with the invasive treatment of VTE is still limited. In this review, we illustrate the available data on pharmacological and endovascular management of iliofemoral VTE, including therapies such as catheter-directed thrombolysis (CDT), mechanical thrombectomy (PMT), and pharmacomechanical catheter-directed thrombolysis (PCDT).

Background: Venous thromboembolism (VTE) is a term used to compositely describe deep vein thrombosis (DVT) and pulmonary embolism (PE). Overall, the incidence of VTE after major abdominal and pelvic surgery has been reported to be between 10% and 40%. Objective: The aim of this study is to estimate the incidence of post-operative VTE in patients undergoing major abdominal surgery for cancer, to identify risk factors associated with VTE, and to assess available thromboprophylaxis tools. Methods: A Medline and Cochrane literature search from database inception until February 1st, 2021 was performed according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Results: Thirty-one studies met our eligibility criteria and were included in the current review. In total, 435,492 patients were identified and the overall incidence of VTE was 2.19% (95% CI: 1.82-2.38). he following risk factors were associated with VTE: smoking, advanced age (>70 years), a history of diabetes mellitus, American Society of Anesthesiologists’ (ASA) classification of Physical Health class III or IV, a history of cardiovascular or pulmonary disease, a history of DVT or PE, elevated plasma fibrinogen level, c-reactive protein (CRP) level, cancer stage III or IV, postoperative acute respiratory distress syndrome (ARDS), prolonged postoperative hospital stay, previous steroid use, history of Inflammatory Bowel Disease (IBD), heart failure and neoadjuvant and adjuvant chemotherapy. Conclusion: VTE remains an important complication after major abdominal surgery for cancer and seems to increase mortality rates.

Exercise is considered to be a “medicine” due to its modulatory roles in metabolic disorders, such as diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP) increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, as a vitamin B3 metabolite, reduces serum levels and liver contents of triglycerides and cholesterol, and induces lipolysis. It stimulates gluconeogenesis and prohibits liver cholesterol and fatty acid synthesis through the expression of sirtuin1 (SIRT1). It seems that MNAM is not responsible for the actions of NNMT in the adipose tissues as MNAM inhibits the activity of NNMT in the adipose tissue and acts as an inhibitor of its activity. NNMT-MNAM axis is more activated in the muscles of individuals undergoing the high-volume-low-intensity exercise and caloric restriction. Therefore, MNAM could be an important myokine during exercise and fasting where it provides the required energy for muscles through the induction of lipolysis and gluconeogenesis in the liver and adipose tissues, respectively. Increased levels of MNAM in exercise and fasting led us to propose that the consumption of MNAM during training, especially endurance training, could boost exercise capacity and improve performance. Therefore, in this review, we shed light on the potential of MNAM as a dietary supplement in sports medicine.

Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS) are neurological disorders pathologically characterized by chronic degeneration of dopaminergic neurons and motor neurons, respectively. There is still no cure or effective treatment against the disease progression and most of the treatments are symptomatic. The present review offers an overview of the different factors involved in the pathogenesis of these diseases. Subsequently, we focused on the recent advanced studies of dietary polyphenols and stem cell therapies, which have made it possible to slow down the progression of neurodegeneration. To date, stem cells and different polyphenols have been used for the directional induction of neural stem cells into dopaminergic neurons and motor neurons. We have also discussed their involvement in the modulation of different signal transduction pathways and growth factor levels in various in vivo and in vitro studies. Likewise stem cells, polyphenols also exhibit the potential of neuroprotection by their anti-apoptotic, anti-inflammatory, and anti-oxidant properties regulating the growth factors levels and molecular signaling events. Overall this review provides a detailed insight into recent strategies that promise the use of polyphenol with stem cell therapy for the possible treatment of PD and ALS.

Background: Several natural/synthetic molecules having a structure similar to 1H-isochromen- 1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of the molecular framework, has been explored for its antioxidant or antiplatelet activities. Introduction: Based on the literature, a new prototype, i.e., 3-phenyl-1H-isochromen-1-ones based compounds, has been rationalized to possess both antioxidant as well as antiplatelet activities. Consequently, no reports are available regarding its inhibition either by cyclooxygenase-1 (COX-1) enzyme or by arachidonic acid (AA)-induced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxidant and antiplatelet agents. Methods: The goal of this work was to identify new 3-phenyl-1H-isochromen-1-ones based compounds via synthesis of a series of analogues, followed by performing in vitro antioxidant as well as AA-induced antiplatelet activities. Then, identification of potent compounds by SAR and molecular docking studies was carried out. Results: Out of all synthesized 3-phenyl-1H-isochromen-1-ones analogues, five compounds showed 7-fold to 16-fold more highly potent antioxidant activities than ascorbic acid. Altogether, ten 3-phenyl-1H-isochromen- 1-one analogues displayed antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Almost all the 3-phenyl-1H-isochromen-1-one analogues exhibited potent AA-induced antiplatelet activity; few of them displayed 7-folds more activity as compared to aspirin. Further, in silico analysis validated the wet results. Conclusion: We disclose the first detailed study for the identification of 3-phenyl-1H-isochromen-1-one analogues as highly potent antioxidant as well as antiplatelet agents. The article describes the scaffold designing, synthesis, bioevaluation, structure-activity relationship, and in silico studies of a pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.

Background: Keratin is among the most abundant structural proteins of animal origin, however it remains broadly underutilized. Objective: Bioinformatic investigation was performed to evaluate selected keratins originating from mass-produced waste products, i.e., chicken feathers and pig hair, as potential sources of bioactive peptides. Methods: Pepsin, trypsin, chymotrypsin, papain, and subtilisin were used for in silico keratinolysis with the use of “Enzyme(s) action” and fragmentomic analysis of theoretical products was performed using “Profiles of potential biological activity” in BIOPEP-UWM database of bioactive peptides. Bioactivity probability calculation and toxicity prediction of the peptides obtained were estimated using PeptideRanker and ToxinPred tools, respectively. Results: Our results showed that the keratins are a potential source of a variety of biopeptides, including dipeptidyl peptidase IV, angiotensin converting enzyme, prolyl endopeptidase inhibitory and antioxidative. Papain and subtilisin were found to be the most appropriate enzymes for keratin hydrolysis. This study presents possible structures of keratin-derived bioactive peptides that have not been previously described. Conclusion: Our data suggest additional in vitro and in vivo studies to verify theoretical predictions and further investigate the possibility of using keratin-rich waste as a source of peptide nutraceuticals.