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Topic Review
Clozapine, Pharmacogenetic Biomarkers, Particularities COVID-19
Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed andWeb of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor then the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.
  • 1.1K
  • 20 Nov 2020
Topic Review
Extracellular Vesicle-based Therapeutics
This is a entry of recent developments of bio-inspired drug delivery systems based on extracellular vesicles (EVs). The main hurdles and limitations for therapeutic and clinical applications of EV-based formulations and various attempts to solve these problems are described. 
  • 1.1K
  • 09 Dec 2020
Topic Review
Chitosan-Based Nano-Smart Drug Delivery System in Breast Cancer
Chitosan nanoparticles (CSNPs) have prospects as a revolutionary delivery system capable of enhancing anticancer drug activity and reducing negative impacts on normal cells. The use of smart drug delivery systems (SDDs) as delivering materials to improve the bioactivity of NPs and to understand the intricacies of breast cancer has garnered significant interest. 
  • 1.1K
  • 16 May 2023
Topic Review
Therapeutic Potential of Ulotaront for Neuropsychiatric Disorders
SEP-363856 (International Nonproprietary Name: Ulotaront) is an investigational antipsychotic drug with a novel mechanism of action that does not involve antagonism of dopamine D2 receptors. Ulotaront is an agonist of trace amine-associated receptor 1 and serotonin 5-HT1A receptors, but can modulate dopamine neurotransmission indirectly. In 2019, the United States Food and Drug Administration granted Breakthrough Therapy Designation for ulotaront for the treatment of schizophrenia.
  • 1.1K
  • 27 Jul 2023
Topic Review
PDE2A for Mouse Liver Development
cAMP and cGMP are intracellular signaling molecules produced in response to a plethora of extracellular signals in order to coordinate cellular metabolism, proliferation, differentiation and apoptosis. Phosphodiesterases (PDEs) are the enzymes that hydrolyze cAMP and cGMP in order to end or to limit the responses to these signals. To date 11 PDE families (named PDE1 to PDE11) have been identified across each cell type expressed in a peculiar pattern. They enclose 21 genes that codify approximately 100 enzymes that form a redundant network ensuring the compensation of activity in case of alteration of activity or lack of expression of one of the members. PDE2A, a cAMP-hydrolyzing enzyme, represents the exception to this picture, as PDE2A knockout is embryonic lethal. Knockout embryos show that the lack of the enzyme has the greatest impact on the development of the heart and of the liver, which is no longer able to assume its hematopoietic role. The increase of the intracellular cAMP level and the downregulation of the anti-apoptotic gene Bcl2 might explain the loss of integrity in the PDE2A knockout liver niche that compromises the hematopoietic function and maturation.
  • 1.1K
  • 29 Oct 2020
Topic Review
Bioactive Phytochemicals from Ruta angustifolia Pers.
The genus Ruta in the family Rutaceae includes about 40 species, such as the well-known plants R. graveolens L. (common rue) or R. chalepensis L. (fringed rue), but also much lesser-known species such as R. angustifolia Pers. (narrow-leaved fringed rue). This rue specie, originating from the Mediterranean region, is well-distributed in Southeast Asia, notably in the Indo-Chinese peninsula and other territories. In some countries, such as Malaysia, the plant is used to treat liver diseases and cancer. Extracts of R. angustifolia display antifungal, antiviral and antiparasitic effects. Diverse bioactive natural products have been isolated from the aerial parts of the plant, notably quinoline alkaloids and furocoumarins, which present noticeable anti-inflammatory, antioxidant and/or antiproliferative properties.
  • 1.1K
  • 23 Feb 2023
Topic Review
Pharmacomicrobiomics and Drug–Infection Interactions
Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. It has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. Additionally, the concept of "drug-infection interaction" is included to describe the influence of pathogenic microorganisms on drug response. This entry analyzes in detail each of these concepts.
  • 1.1K
  • 05 Jan 2024
Topic Review
Vertebral Fractures in HIV-Infected Patients
HIV-infected patients show high risk of fracture. The aims of our study were to determine the prevalence of vertebral fractures (VFs) and their associations with vitamin D in HIV patients. 100 patients with HIV infection and 100 healthy age- and sex-matched controls were studied. Bone mineral density was measured by quantitative ultrasound at the non-dominant heel. Serum osteocalcin and C-terminal telopeptide of collagen type 1 served as bone turnover markers. Bone ultrasound measurements were significantly lower in patients compared with controls (Stiffness Index (SI): 80.58 ± 19.95% vs. 93.80 ± 7.10%, respectively, p < 0.001). VFs were found in 16 patients and in 2 controls. HIV patients with vertebral fractures showed lower stiffness index (SI) (70.75 ± 10.63 vs. 83.36 ± 16.19, respectively, p = 0.045) and lower vitamin D levels (16.20 ± 5.62 vs. 28.14 ± 11.94, respectively, p < 0.02). The majority of VFs (87.5%) were observed in HIV-infected patients with vitamin D insufficiency, and regression analysis showed that vitamin D insufficiency was significantly associated with vertebral fractures (OR 9.15; 95% CI 0.18–0.52, p < 0.04). VFs and are a frequent occurrence in HIV-infected patients and may be associated with vitamin D insufficiency.
  • 1.1K
  • 03 Nov 2020
Topic Review
Dinoflagellate Phycotoxins
Dinoflagellates are single-celled eukaryotes constitute an important group of phytoplanktons, characterized by two dissimilar flagella and distinctive features of both plants and animals.
  • 1.1K
  • 30 Dec 2020
Topic Review
Biomarkers Derived from the Molecular Profiling of TNBC
Triple-negative breast cancer (TNBC), the most aggressive and heterogenous type of cancer, lacks the expression of hormones like estrogen, progesterone, and human epidermal growth receptor-2, making chemotherapy the only treatment regimen against TNBC. To overcome the problem faced during chemotherapy, and to address the heterogeneity of TNBC, targeted therapy emerged based on the molecular profiling of TNBC. Several biomarkers are used as targets for the precision therapy in TNBC, including EGFR, VGFR, TP53, interleukins, insulin-like growth factor binding proteins, c-MET, androgen receptor, BRCA1, glucocorticoid, PTEN, ALDH1, etc.
  • 1.1K
  • 16 Aug 2023
Topic Review
Metformin in Type 2 Diabetes
Metformin is the most commonly used glucose-lowering therapy (GLT) worldwide and remains the first-line therapy for newly diagnosed individuals with type 2 diabetes (T2D) in management algorithms and guidelines after the UK Prospective Diabetes Study (UKPDS) showed cardiovascular mortality benefits in the overweight population using metformin.
  • 1.1K
  • 21 Jan 2021
Topic Review
Polymer-Based Nanovaccines
Polymer-based particles have found application as vaccine platforms and vaccine adjuvants due to their ability to prevent antigen degradation and clearance, coupled with enhanced uptake by professional antigen-presenting cells (APCs). Polymeric nanoparticles have been applied in vaccine delivery, showing significant adjuvant effects as they can easily be taken up by APCs. In other words, polymer-based systems offer a lot of advantages, including versatility and flexibility in the design process, the ability to incorporate a range of immunomodulators/antigens, mimicking infection in different ways, and acting as a depot, thereby persisting long enough to generate adaptive immune responses. 
  • 1.1K
  • 03 Jun 2021
Topic Review
Pharmacogenetic Testing
Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician’s ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.
  • 1.1K
  • 07 Jan 2021
Topic Review
Pharmacology of Biosimilars
Testing in animals is an old routine used for new drugs to avoid serious toxicity to humans. However, biological drugs may not always show a pharmacologic response in animal species; thus, the toxicity is an extension of the pharmacological response for biological drugs. Clinical pharmacology comparisons comprise the most relevant testing to support the biosimilarity of a biosimilar candidate. When a novel drug is developed, PK/PD testing is carried out on many volunteers to understand the diversity of disposition in terms of gender, age, and genetic distribution.
  • 1.1K
  • 27 Apr 2022
Topic Review
Nanoparticles in the Intestinal Epithelial Cell Membrane
Intestinal epithelial cells are the most abundant epithelial cells in the intestine, accounting for 90–95% of intestinal cells. They are columnar cells with hair-like projections called microvilli on the apical membrane, which greatly increase the surface area available for absorption. The transintestinal cell pathway refers to the process in which nanoparticles pass through apical and basolateral membranes via intercellular transport and then discharge from the basement membrane to the extracellular space. The entire process can be divided into three stages: the uptake of nanoparticles in the apical membrane of intestinal epithelial cells, the transport of endosomes in the cytoplasm and the exocytosis of nanoparticles in the basement membrane.
  • 1.1K
  • 05 Jul 2023
Topic Review
Transient Receptor Potential
The superfamily of ion channels named transient receptor potential (TRP) acts as sensors of oxidative compounds at the plasma membrane and can amplify several signaling. The TRP superfamily is a non-selective cation channel initially identified in the Drosophila fly species. These channels are presented in different cell types and tissues, such as epithelial, immune, and neuronal cells.
  • 1.1K
  • 12 Jan 2023
Topic Review
Therapeutic Sequencing in ALK+ NSCLC
Anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC) is a model disease for the use of targeted pharmaceuticals in thoracic oncology. This entry summarizes the state-of-the-art treatment for these tumors as of January 2021, with a special emphasis in the sequential use of various compounds as well as the growing importance of molecular profiling and monitoring for patient management.
  • 1.1K
  • 20 Apr 2021
Topic Review
Opioid Analgesia and Opioid-Induced Adverse Effects
Opioids are broadly used as therapeutic agents against moderate to severe acute and chronic pain. Noticeably, these analgesics have many limitations as they induce analgesic tolerance, addiction, physical dependence, respiratory depression, and various other behavioural adverse effects that often result in patient non-compliance. In addition, the actual mechanisms of opioid-induced adverse reactions over long-term use are not entirely understood. 
  • 1.1K
  • 08 Dec 2021
Topic Review
FUBCs in gram negative bacteremia
Bloodstream infections still constitute an outstanding cause of in-hospital morbidity and mortality, especially among critically ill patients. Follow up blood cultures (FUBCs) are widely recommended for proper management of Staphylococcus aureus and Candida spp infections. On the other hand, their role is still a matter of controversy as far as Gram negative bacteremias are concerned. We revised, analyzed, and commented on the literature addressing this issue, to define the clinical settings in which the application of FUBCs could better reveal its value.
  • 1.1K
  • 29 Dec 2020
Topic Review
Lipophilic Polyamines
Gene therapy requires an effective and safe delivery vehicle for nucleic acids. Non-viral vehicles, including cationic liposomes, are intensively developed now. The structure of compounds composing them determines the delivery efficiency a lot. This review focuses on polycationic amphiphiles as prospective compounds for liposomal formulations and includes a discussion of the mutual influence of structural components. 
  • 1.1K
  • 11 Aug 2021
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