Liver Diseases
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
In the mechanism of hemoglobin breakdown to bilirubin, several intermediates have been suggested (Figure 16). Hematin is considered to be a normal intermediary. In intravascular hemolysis such as hematin icterus, the production of hematin is increased without bilirubin elevation. Lack of hyperbilirubinemia suggests a shift in the normal metabolism to the accumulation of hematin. Animal experiments using labeled hemin are in agreement with the formation of this intermediate. The formation of choleglobin or verdohemoglobin, a green iron-containing protein complex, has also been proposed. By successive oxidation, the α-methene bridge is replaced by an ether bond. The next step leads to loss of iron and protein, and the biliverdin formed is reduced to bilirubin. The presence of biliverdin reductase and heme-α-methenyl oxygenase in the liver and kidney provides evidence for the existence of this pathway. Verdoglobinuria occurs in Pseudomonas septicemia, indicating that the bacterial toxin interferes with the complete metabolism of hemoglobin, resulting in the accumulation of verdoglobin.418,533
H
Anton Sebastian in A Dictionary of the History of Medicine, 2018
Hemin Chloride of ferric protoporphyrin or hematin in blood, first used as an indicator for detection of blood in forensic medicine by German histologist, Ludwig Teichmann (1823–1895) in 1853. He treated the blood sample or material with acetic acid and sodium chloride in order to reveal the formation of hemin in positive cases. This was used in legal medicine for over a century.
The structure of CLEC-2: mechanisms of dimerization and higher-order clustering
Published in Platelets, 2021
Eleyna M Martin, Malou Zuidscherwoude, Luis a Morán, Ying Di, Angel García, Steve P Watson
Bourne et al [5]. recently identified hemin as an endogenous ligand for CLEC-2. Hemin, the oxidized form of heme, is a protoporphyrin IX containing an Fe3+ ion with an associated chloride ligand, structure displayed in Figure 5. Hemin is found in the bloodstream during hemolytic conditions during which prothrombotic and proinflammatory responses are induced. The work of Bourne et al [5]. demonstrated that hemin is able to activate human and mouse platelets through direct binding to CLEC-2. They revealed that hemin at low micromolar concentrations induced rapid aggregation of human platelets in association with phosphorylation of Syk and PLCγ2, and that aggregation was blocked by inhibitors of Syk, SFKs and Btk consistent with an ITAM receptor-based pathway. SPR was used to confirm direct binding to CLEC-2 and determine the affinity of hemin to dimeric Fc-fusion human and mouse CLEC-2 to be in the order of 200 nM. Platelet aggregation induced by hemin was not blocked by anti-human CLEC-2 monoclonal antibody AYP1 suggesting that hemin binds to a site distinct from rhodocytin and podoplanin, which compete with AYP1 for CLEC-2 binding (discussed further below)[17].
Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis
Published in Gut Microbes, 2022
Qichen Shen, Zhuizui Huang, Lingyan Ma, Jiachen Yao, Ting Luo, Yao Zhao, Yingping Xiao, Yuanxiang Jin
Fresh fecal samples from the control and DSS groups were homogenized with 0.1 M anaerobic phosphate-buffered saline (PBS) and centrifuged at 1000 g for 20–30 s to remove undigested food particles. The suspension was centrifuged (8000 g) and washed twice in PBS before being resuspended in the same volume of PBS to make 10% (w/v) slurries. The growth media for in vitro fermentation was basic growth medium (YCFA) that was prepared as described previously and contained the following: 10 g/L tryptone, 2.5 g/L yeast extract, 1 g/L L-cysteine, 0.9 g/L NaCl, 0.09 g/L CaCl2 · 6 H2O, 0.45 g/L KH2PO4, 0.45 g/L K2HPO4, 0.09 g/L MgSO4 · 7H2O, 2 ml of vitamin I and hemin solution. The vitamin I solution contained the following components: 0.05 mg/ml vitamin B8, 0.05 mg/ml vitamin B12, 0.15 mg/ml acid 4-aminobenzoïque, 0.25 mg/ml vitamin B9 and 0.75 mg/ml pyridoxamine. The hemin concentration was 1 mg/ml in 1 M sodium hydroxide.62 Four milliliters of the fecal slurry were inoculated into 40 ml of growth medium and subjected to anaerobic fermentation under anaerobic conditions in an anaerobic workstation (80% N2, 10% CO2 and 10% H2). After 24 h of fermentation, miRNAs mimics were added and fermented for another 24 h. The precipitate and supernatant were collected for 16S rRNA gene analysis and extracellular vesicle (EV) isolation respectively.
Givosiran for the treatment of acute hepatic porphyria
Published in Expert Review of Clinical Pharmacology, 2022
Andrea Ricci, Paolo Ventura
Current management options for AIP focus on lifestyle changes and reducing triggers for recurrent attacks. Lifestyle changes, such as managing stress and avoiding strict diets, are recommended as measures for preventing attacks so as not to precipitate elevations in ALAS1 activity and the toxic porphyrin precursors [12,23]. Hemin infusions are often used to treat ongoing attacks or to prevent recurrent attacks [24]. Hemin is approved for use in women with AIP attacks related to the menstrual cycle after carbohydrate therapy was shown to be inadequate [21,25]. With the approval of givosiran, the armamentarium against AHPs dramatically improved by including a treatment which has shown to significantly reduce porphyric attacks. This article provides an overview of the clinical and pharmacological profile of givosiran, an RNA interference therapeutic, for the treatment of adults with AHPs.
Related Knowledge Centers
- Chloride
- Heme
- Hydroxide
- Iron
- Porphyrin
- Hemoglobin
- Red Blood Cell
- Heme B
- Protoporphyrin Ix
- Coordination Complex