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Topic Review
Clinical Studies in IGU
Iguratimod (IGU) is a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) routinely prescribed in Japan since 2012 to patients with rheumatoid arthritis (RA). Iguratimod acts directly on B cells by inhibiting the production of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, IL-17), thereby suppressing the production of immunoglobulin and inhibiting the activity of nuclear factor kappa-light chain enhancer of activated B cells. In Japan, it is one of the most used csDMARDs in daily practice, but it is not recommended as a treatment for RA due to the lack of large-scale evidence established overseas.
  • 397
  • 01 Jun 2021
Topic Review
Clinical Trials of Parkinson’s Disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that currently has no cure, but treatments are available to improve PD symptoms and maintain quality of life.
  • 851
  • 03 Aug 2021
Topic Review
Clopidogrel Resistance (CR)
Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. 
  • 506
  • 07 May 2021
Topic Review
Clotting Dysfunction in Sepsis
Sepsis is regarded as one of the main causes of death among the critically ill. Pathogen infection results in a host-mediated pro-inflammatory response to fight infection; as part of this response, significant endogenous reactive oxygen (ROS) and nitrogen species (RNS) production occurs, instigated by a variety of sources, including activated inflammatory cells, such as neutrophils, platelets, and cells from the vascular endothelium. Inflammation can become an inappropriate self-sustaining and expansive process, resulting in sepsis. Patients with sepsis often exhibit loss of aspects for normal vascular homeostatic control, resulting in abnormal coagulation events and development of disseminated intravascular coagulation. Diagnosis and treatment of sepsis remains a significant challenge for health care providers globally. Targeting the drivers of excessive oxidative/nitrosative stress using antioxidant treatments might be a therapeutic option.
  • 322
  • 14 Jan 2022
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.
  • 594
  • 20 Nov 2020
Topic Review
CO2 Pneumoperitoneum
Laparoscopy (LS) has been shown to decrease the inflammatory sequelae of endotoxemia. β-arrestin 2 plays an important function in signal transduction pathway of TLR4. High mobility group box-1 (HMGB-1) is involved in the delayed systemic inflammatory response. We investigated the effects of CO2 insufflation on liver, lung, and kidney expression of both β-arrestin 2 and HMGB-1 during sepsis. Cecal ligation and puncture (CLP) was performed in male rats and 6 h later the animals were randomly assigned to receive a CO2 pneumoperitoneum or laparotomy. Animals were euthanized; liver, lung, and kidney were removed for the evaluation of β-arrestin 2 and HMGB-1 expression. Immunohistochemical detection of myeloperoxidase (MPO) was investigated in lung and liver and bacterial load was determined in the peritoneal fluid. CO2 pneumoperitoneum reduced peritoneal bacterial load, increased the expression of β-arrestin 2, and blunted the expression of the potent proinflammatory HMGB-1 in liver, lung, and kidney compared with laparotomy. Liver and lung MPO was markedly reduced in rats subjected to LS compared with laparotomy. We believe that CO2 exerts an early protective effect by reducing bacterial load and likely toll-like receptor activation which in turn leads to a preserved β-arrestin 2 expression and a reduced HMGB-1 expression.
  • 898
  • 02 Nov 2020
Topic Review
Cobalt–Chromium Dental Alloys
Co–Cr dental alloys consist of Co, Cr and also other metals (e.g., gallium, iron, molybdenum, nickel, ruthenium, tungsten). Since the 1990s, regulations have emerged to protect European patients and also monitor recent scientific knowledge. The use of metals and, therefore, dental alloys has been highly regulated by directives and regulations. Europe has, therefore, developed a regulatory package to protect all players involved in alloys, whether they are metal producers, manufacturers of alloys and medical devices, healthcare professionals and patients. Objective information is provided about Co–Cr dental alloys, with regard to both the latest toxicological data and regulatory developments from 2020–2025. The release of metal ions and the problem of wear particles are also discussed. With the recent change of regulatory status of Co, it is necessary to know the many repercussions (economic, technical etc.) of their use precisely in order to then allow actors to modify their daily work. The legislative changes also bring the need to propose new alternatives to Co-Cr dental alloys.  
  • 1.0K
  • 21 Jan 2021
Topic Review
Colloidal Systems
Preparing a suitable formulation for parenteral administration is already a difficult task; this, coupled with poor water-soluble new chemical entity (NCE), complicates this situation even further. Making a micro/nano emulsion with a suitable surfactant not only increases the drug solubility but also the cell membrane permeability. This succinct entry delves into various aspects of biphasic micro/nano emulsion systems for parenteral drug delivery including the structure of the biphasic colloidal systems, characterization parameters, stability issues, regulatory considerations, and applications in life sciences.
  • 983
  • 20 Feb 2021
Topic Review
Combination Therapies in Alzheimer’s Disease
Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. It is indeed difficult to combine several pharmacophores into a single molecule.  It is essential to carry out long-duration randomized controlled trials to establish whether CT delays disease progression in early AD stages. Other factors also need to be assessed in CT, such as its potential neuroprotective effects, cost-effectiveness, and a more exhaustive estimation of its potential benefits on the patients at the end-stage of AD.
  • 805
  • 28 Oct 2020
Topic Review
Combination Therapy for Glioblastoma
Aggressive glioblastoma (GBM) has no known treatment as a primary brain tumor. Since the cancer is so heterogeneous, an immunosuppressive tumor microenvironment (TME) exists, and the blood–brain barrier (BBB) prevents chemotherapeutic chemicals from reaching the central nervous system (CNS), therapeutic success for GBM has been restricted. Drug delivery based on nanocarriers and nanotechnology has the potential to be a handy tool in the continuing effort to combat the challenges of treating GBM. Combination therapies may be enhanced by using nanotechnology-based delivery techniques. Nano-chemotherapy, nano-chemotherapy–radiation, nano-chemotherapy–phototherapy, and nano-chemotherapy–immunotherapy for GBM.
  • 605
  • 02 Nov 2022
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