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Topic Review
Cholestatic Diseases
Cholestatic diseases are based on bile dysfunction due to defects affecting bile synthesis or secretion. These processes involve a wide range of enzymes and membrane transporters involved in hepatobiliary circulation. According to its origin, cholestasis can be classified into two main groups: acquired cholestasis and genetic cholestasis.
  • 685
  • 10 Jun 2022
Topic Review
Cholestatic Pruritus in Children
Pruritus in the setting of cholestatic liver disease is difficult to treat and occurs in patients ranging in age from infancy to adulthood. Likely multifactorial in etiology, this symptom often involves multimodal therapy targeting several pathways and mechanisms proposed in the underlying etiology of cholestatic pruritus. Conventional therapies for the treatment of cholestatic pruritus in children include ursodeoxycholic acid, cholestyramine, hydroxyzine, and rifampin. Therapies used in the adult population with limited data in pediatric patients include opioid antagonists and selective serotonin reuptake inhibitors. Ileal bile acid transport inhibitors have been shown to alleviate pruritus in many children with Alagille syndrome and progressive familial intrahepatic cholestasis and it is an additional therapy available for consideration for these patients. Ultimately, surgical management and liver transplantation are considered in select refractory cases.
  • 422
  • 14 Jun 2023
Topic Review
Cholesterol-to-Coprostanol Conversion
Cholesterol (examples of synonyms 3β-hydroxy-5-cholestene or 5-cholesten-3β-ol) in the intestine may be either absorbed or undergo microbial conversion to different metabolites, of which non-absorbable coprostanol (examples of synonyms 5β-cholestanol or 5β-cholestan-3β-ol) is the end and predominant product found in feces. Note that multiple synonyms can be employed for a same steroid molecule, which does not help the reader to find his way. Cholesterol is a 27-carbon molecule with a structure formed by a polycyclic ring skeleton with a trans A/B ring junction, a β-hydroxyl group in the equatorial position at C3 (i.e., in plane of the molecule), a double bond at C5 (Δ5double bond), two methyl groups at C10 and C13, and a side chain at C17 (A).
  • 788
  • 26 Sep 2021
Topic Review
Chromosomal Instability and Its Role in Therapeutics Response
Variation in chromosome structure is a central source of DNA damage and DNA damage response, together representinga major hallmark of chromosomal instability. Treatment of cancer usually includes surgery, radiotherapy, or chemotherapy. The activity of radiotherapy and most chemotherapy drugs induces DNA damage in proliferating tumor cells. For example, platinum drugs that are effective against cancer cells form DNA adducts. Other drugs, such as anthracyclines induce DNA damage by inhibiting DNA topoisomerases and promoting the production of mitochondrial reactive oxygen species (ROS). In normal cells, DNA damage can be immediately recognized by a DNA damage response (DDR), which activates checkpoints for cell-cycle arrest and DNA repair. In cancer cells, DNA damage per se may be responsible for defective chromosome segregation and chromosomal instability (CIN) or the anomalous binding of DDR proteins to DNA or chromatin proteins. 
  • 554
  • 11 Jan 2023
Topic Review
Chronic Inflammatory Bowel Diseases
Susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases (IBD) are unclear and epidemiological data on the topic are still limited. There is some concern that patients with immuno-mediated diseases such as IBD, which are frequently treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 infection with its related serious adverse outcomes, including intensive care unit (ICU) admission and death. Corticosteroids, immunomodulators, and biologic drugs, which are commonly prescribed to these patients, have been associated with higher rates of severe viral and bacterial infections including influenza and pneumonia. It is not known whether these drugs can be so harmful as to justify their interruption during COVID-19 infection or if, on the contrary, patients with IBD can benefit from them. As shown by recent reports, it cannot be excluded that drugs that suppress the immune system can block the characteristic cytokine storm of severe forms of COVID-19 and consequently reduce mortality. Another cause for concern is the up-regulation of angiotensin converting enzyme-2 (ACE2) receptors that has been noticed in these patients, which could facilitate the entry and replication of SARS-CoV-2. The aim of this narrative review is to clarify the susceptibility of SARS-CoV-2 infection in patients with IBD, the clinical characteristics of patients who contract the infection, and the relationship between the severity of COVID-19 and immunosuppressive treatment. 
  • 474
  • 08 Oct 2021
Topic Review
CircRNAs in Liver Fibrosis
Liver fibrosis represents the reversible pathological process with the feature of the over-accumulation of extracellular matrix (ECM) proteins within the liver, which results in the deposition of fibrotic tissues and liver dysfunction. Circular noncoding RNAs (CircRNAs) have the characteristic closed loop structures, which show high resistance to exonuclease RNase, making them far more stable and recalcitrant against degradation. CircRNAs increase target gene levels by playing the role of a microRNA (miRNA) sponge.
  • 234
  • 19 Sep 2023
Topic Review
Circulating Adaptive Immune Cells in End-Stage Liver Disease
End-stage liver disease (ESLD) from acute liver failure to compensated advanced chronic liver disease and decompensated cirrhosis at different stages (chronic decompensation, acute decompensation with or without acute-on-chronic liver failure) has high disease severity and poor patient outcome. Infection is a common complication in patients with ESLD and it is associated with a high mortality rate. Multiple mechanisms are involved in this marked susceptibility to infections, noticeably the inadequate immune response known as immune paresis, as part of cirrhosis-associated immune dysfunction (CAID). Specifically in the adaptive immune arm, lymphocyte impairments—including inadequate activation, reduced ability to secrete effector molecules and enhanced immune suppressive phenotypes—result in compromised systemic immune responses and increased risk of infections. 
  • 199
  • 08 Aug 2023
Topic Review
Circulating Biomarkers Involved in Chronic Pancreatitis
Chronic pancreatitis (CP) is the end-stage of continuous inflammation and fibrosis in the pancreas evolving from acute- to recurrent acute-, early, and, finally, end-stage CP. Currently, prevention is the only way to reduce disease burden. In this setting, early detection is of great importance. Due to the anatomy and risks associated with direct sampling from pancreatic tissue, most of the information on the human pancreas arises from circulating biomarkers thought to be involved in pancreatic pathophysiology or injury. 
  • 272
  • 27 Feb 2024
Topic Review
Circulating Tumor Cells in Colorectal Cancer
Circulating tumor cells (CTCs)  are intact cells separated from the primary tumor or metastases and released into the peripheral circulation. They were observed and discovered for the first time in 1869 in the blood of a patient with breast cancer. CTCs mainly originate from solid tumors of epithelial origin (breast, prostate, colon, and lung). CTCs are nucleated and express epithelial cell adhesion molecules (EpCAM) and/or cytokeratins (CK) in the cytoplasm without coexpressing the common leukocyte antigen CD45. It is known today that there is significant heterogeneity in cell species and surface markers, which represents a challenge in isolating all clinically relevant subpopulations of CTCs.
  • 534
  • 22 Nov 2022
Topic Review
Cirrhotic Cardiomyopathy
Cirrhotic cardiomyopathy (CCM), cardiac dysfunction in end-stage liver disease in the absence of prior heart disease, is an important clinical entity that contributes significantly to morbidity and mortality. The original definition for CCM, established in 2005 at the World Congress of Gastroenterology (WCG), was based upon known echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Subsequent advances in cardiovascular imaging and in particular myocardial deformation imaging have rendered the WCG criteria outdated. A number of investigations have explored other factors relevant to CCM, including serum markers, electrocardiography, and magnetic resonance imaging. CCM characteristics include a hyperdynamic circulatory state, impaired contractility, altered diastolic relaxation, and electrophysiological abnormalities, particularly QT interval prolongation. It is now known that cardiac dysfunction worsens with the progression of cirrhosis. Treatment for CCM has traditionally been limited to supportive efforts, but new pharmacological studies appear promising. Left ventricular diastolic dysfunction in CCM can be improved by targeted heart rate reduction. Ivabradine combined with carvedilol improves left ventricular diastolic dysfunction through targeted heart rate reduction, and this regimen can improve survival in patients with cirrhosis. Orthotopic liver transplantation also appears to improve CCM. 
  • 599
  • 12 Oct 2021
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