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Alcoholic Liver Disease
Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis. It is the major cause of liver disease in Western countries, and is the leading cause of death from excessive drinking. Although steatosis ( fatty liver disease) will develop in any individual who consumes a large quantity of alcoholic beverages over a long period of time, this process is transient and reversible. More than 90% of all heavy drinkers develop fatty liver whilst about 25% develop the more severe alcoholic hepatitis, and 15% liver cirrhosis. For patients with chronic hepatitis B, a strict adherence to abstinence from alcohol is highly recommended. Presentation Risk factors As of 2010, known risk factors of ALD are: * Quantity of alcohol taken: Consumption of 60–80 g per day (14 g is considered ...
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Microscopy
Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical microscope, optical, electron microscope, electron, and scanning probe microscopy, along with the emerging field of X-ray microscopy. Optical microscopy and electron microscopy involve the diffraction, reflection (physics), reflection, or refraction of electromagnetic radiation/electron beams interacting with the Laboratory specimen, specimen, and the collection of the scattered radiation or another signal in order to create an image. This process may be carried out by wide-field irradiation of the sample (for example standard light microscopy and transmission electron microscope, transmission electron microscopy) or by scanning a fine beam over the sample (for example confocal laser scanning microscopy and scanning electron microscopy). Scan ...
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ALDH
Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes. Function Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids. There are three different classes of these enzymes in mammals: class 1 (low ''K''m, cytosolic), class 2 (low ''K''m, mitochondrial), and class 3 (high ''K''m, such as those expressed in tumors, stomach, and cornea). In all three classes, constitutive and inducible forms exist. ALDH1 and ALDH2 are the most important enzymes for aldehyde oxidation, and both are tetrameric enzymes composed of 54 kDa subunits. These enzymes are fou ...
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Inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''dolor'', ''rubor'', ''tumor'', and ''functio laesa''). Inflammation is a generic response, and therefore is considered a mechanism of innate immunity, whereas adaptive immunity is specific to each pathogen. Inflammation is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and initiate tissue repair. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. However inflammation can also have negative effects. Too much inflammation, in the form of chronic inflammation, is associated with variou ...
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Toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (biology), cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). Sometimes the word is more or less synonymous with poison#Poisoning, poisoning in everyday usage. A central concept of toxicology is that the effects of a toxicant are Dose (biochemistry), dose-dependent; even water can lead to water intoxication when taken in too high a dose, whereas for even a very toxic substance such as snake venom there is a dose below which there is no detectable toxic effect. Toxicity is species-specific, making cross-species analysis problematic. Newer paradigms and metrics are evolving to bypass animal testing, while maintaining the concept of toxicity endpoints. Etymology In Ancient G ...
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Acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic compound, organic chemical compound with the chemical formula, formula , sometimes abbreviated as . It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol (drug), alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body. International Agency for Research on Cancer, The International Agency for Research on Cancer (IARC) has listed acetaldehyde ...
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Lipid Peroxidation
Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz , first2=Mario F. , last3=Argüelles , first3=Sandro , date=2014 , title=Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal , journal=Oxidative Medicine and Cellular Longevity , language=en , volume=2014 , pages=1–31 , doi=10.1155/2014/360438 , doi-access=free , issn=1942-0900 , pmc=4066722 , pmid=24999379 It occurs when free radicals, specifically reactive oxygen species (ROS), interact with lipids within cell membranes, typically polyunsaturated fatty acids (PUFAs) as they have carbon–carbon double bonds. This reaction leads to the formation of lipid radicals, collectively referred to as lipid peroxides or lipid oxidation products (LOPs), which in turn react with other ox ...
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Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., (superoxide radical), OH ( hydroxyl radical) and (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the development of attention deficit hyperactivity disorder, cancer, Parkin ...
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Interleukin 8
Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel–Palade bodies. In humans, the interleukin-8 protein is encoded by the ''CXCL8'' gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages. There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response. Functio ...
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Interleukin 6
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF and IL-1 and its activation of IL-1ra and IL-10. There is some early evidence that IL-6 can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis, in the context of the wider coronavirus pandemic. Function Immune system IL-6 is secreted by macrophages in response to specific microbial molecules, referred to as pathogen-associated molecular patterns ( PAMPs). These PAMPs bind to an important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs), includ ...
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TNF-alpha
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells. It is a member of the tumor necrosis factor superfamily, a family of transmembrane proteins that are cytokines, chemical messengers of the immune system. Excessive production of TNF plays a critical role in several inflammatory diseases, and TNF-blocking drugs are often employed to treat these diseases. TNF is produced primarily by macrophages but is also produced in several other cell types, such as T cells, B cells, dendritic cells, and mast cells. It is produced rapidly in response to pathogens, cytokines, and environmental stressors. TNF is initially produced as a type II transmembrane protein (tmTNF), which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF) and secreted from the cell. ...
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Cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes and mast cells, as well as Endothelium, endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptor, cytokine receptors on the target cell surface. Cytokines are especially important in the immune system; cytokines modulate the balance between humoral immunity, humoral and cell-mediated immunity, cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines in complex way ...
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Pathogenesis Alcoholic Liver Injury
In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Description Types of pathogenesis include microbial infection, inflammation, malignancy and tissue breakdown. For example, bacterial pathogenesis is the process by which bacteria cause infectious illness. Most diseases are caused by multiple processes. For example, certain cancers arise from dysfunction of the immune system (skin tumors and lymphoma after a renal transplant, which requires immunosuppression), ''Streptococcus pneumoniae'' is spread through contact with respiratory secretions, such as saliva, mucus, or cough droplets from an infected person and colonizes the upper respiratory tract and begins to multiply. The pathogenic mechanisms of a disease (or condition) are set in motion by the underlying causes, which if controlled would ...
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