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Topic Review
Type 2 Diabetes and P450
 The most frequent form of diabetes is type 2 diabetes mellitus (T2DM) which is often part of a metabolic syndrome (hyperglycaemia, hypertension, hypercholesterolemia, abdominal obesity) that usually requires the use of several medications from different drug classes to bring each of these conditions under control. T2DM is associated with an increase in inflammatory markers such as interleukin-6 (IL-6) and the tumor necrosis factor alpha (TNF-α). Higher levels of IL-6 and TNF-α are associated with a downregulation of several drug metabolizing enzymes, especially the cytochrome P450 (P450) isoforms CYP3As and CYP2C19. A decrease in these P450 isoenzymes may lead to unexpected rise in plasma levels of substrates of these enzymes. It could also give rise to a mismatch between the genotypes determined for these enzymes, the predicted phenotypes based on these genotypes and the phenotypes observed clinically. This phenomenon is described as phenoconversion. Phenoconversion typically results from either a disease (such as T2DM) or concomitant administration of medications inducing or inhibiting (including competitive or non-competitive inhibition) a P450 isoenzyme used by other substrates for their elimination. Phenoconversion could have a significant impact on drug effects and genotypic-focused clinical outcomes.
  • 651
  • 11 Oct 2021
Topic Review
Two-Pore Channels and Ca2+ Homeostasis in Immune Cells
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca2+ from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca2+ signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), were found to trigger the release of Ca2+ from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. 
  • 344
  • 16 May 2022
Topic Review
Two Non-Tablet Oral Formulations of L-Thyroxine
Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. 
  • 388
  • 22 Jul 2022
Topic Review
Tumor Necrosis Factor and Lymphotoxin
The tumor necrosis factor (TNF) ligand family includes 19 ligands, which each contain a C-terminal TNF homology domain (THD). Each ligand binds to one or multiple TNF receptors (TNFR), containing extracellular cysteine-rich domains (CRD) for ligand binding. Tumor necrosis factor (TNF or TNF-α) and lymphotoxin (LT) are the first two cytokines that have been characterized as TNF superfamily members. They have a homologous amino acid sequence and were both discovered based on their anti-tumor effects. Moreover, both ligands bind to TNF receptor type 1 and type 2 (TNFR1 and TNFR2) and mediate similar cell signaling transduction.
  • 638
  • 19 Jan 2022
Topic Review
TRPA1 Role in Inflammatory Disorders
The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized in a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia, where its activation mediates neurogenic inflammatory responses. The TRPA1 pathway could be a protective mechanism to detect and respond to harmful agents in various pathological conditions, including several inflammatory diseases.
  • 342
  • 09 May 2022
Topic Review
Trientine in Hypertrophic Cardiomyopathy
Trientine, a copper-chelating drug used in the management of patients with Wilson’s disease, demonstrates beneficial effects in patients with hypertrophic cardiomyopathy.
  • 439
  • 10 Feb 2023
Topic Review
Treatment Options of Helicobacter pylori
Helicobacter pylori is among the most common infections worldwide, and it can lead to burdensome sequela for the patient and the healthcare system, without appropriate treatment. Due to constantly fluctuating resistance rates, regimens must be constantly assessed to ensure effectiveness. 
  • 517
  • 21 Dec 2022
Topic Review
Treatment of Stimulant Use Disorder
The increasing prevalence of stimulant use disorder (StUD) involving methamphetamine and cocaine has been a growing healthcare concern in the United States. Cocaine usage is associated with atherosclerosis, systolic and diastolic dysfunction, and arrhythmias. 
  • 298
  • 10 Mar 2023
Topic Review
Treatment of Endometriosis
Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues inside and outside the pelvic cavity. The evolution of the disease can lead to infertility in addition to high treatment costs. The available medications are only effective in treating endometriosis-related pain.   
  • 788
  • 12 Jul 2022
Topic Review
Treatment of  Rheumatoid Arthritis
Rheumatoid arthritis refers to joint diseases of unclear etiology whose final stages can lead to unbearable pain and complete immobility of the affected joints. Modern treatment with anti-inflammatory drugs, including janus kinase (JAK) inhibitors, monoclonal antibodies, and botanicals (polyphenols, glycosides, alkaloids, etc.) has achieved some success and hope for improving the course of the disease. 
  • 240
  • 30 Oct 2023
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