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Precipitation and Co-precipitation01:17

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Precipitation and coprecipitation methods can be used to separate a mixture of ions in a solution. In qualitative inorganic analysis, ions that form sparingly soluble precipitates with the same reagent are separated based on the differences in solubility products. For example, consider the separation of Cu(II) and Fe(II) ions by precipitation as insoluble sulfides. First, copper(II) sulfide is precipitated by the addition of acidic H2S, where the dissociation of H2S is suppressed. Adding H2S...
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Phase II Reactions: Miscellaneous Conjugation Reactions01:19

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Phase II biotransformations are detoxification mechanisms that conjugate xenobiotics with endogenous substances, neutralizing their toxicity.
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
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Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

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Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme...
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Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions01:20

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Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
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Formation of Complex Ions03:45

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A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
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Extraction: Advanced Methods00:56

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Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is...
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Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders
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Disulfiram with Cu

Wei Zhou1,2, Hua Zhang3, Lihua Huang1,2

  • 1The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, Guangdong, China.

Theranostics
|June 7, 2023
PubMed
Summary

Disulfiram plus copper (DSF+Cu2+) shows promise in preventing and treating ulcerative colitis (UC) by reducing inflammation and improving gut health. This combination therapy offers a potential new treatment for inflammatory bowel disease (IBD).

Keywords:
CD4+ T cellsdisulfirammacrophagemicrobiotaulcerative colitis

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Area of Science:

  • Immunology
  • Gastroenterology
  • Pharmacology

Background:

  • Inflammatory bowel diseases (IBD), including ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation.
  • Current IBD treatments face challenges with side effects and cost, necessitating novel therapeutic approaches.
  • Disulfiram (DSF), an FDA-approved drug, exhibits anti-inflammatory properties, which can be enhanced by copper (Cu2+).

Purpose of the Study:

  • To investigate the preventive effects of Disulfiram plus copper (DSF+Cu2+) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in a mouse model.
  • To elucidate the underlying mechanisms of DSF+Cu2+ in modulating immune responses and intestinal microecology in UC.

Main Methods:

  • Utilized a DSS-induced colitis mouse model and lipopolysaccharide (LPS)-stimulated macrophages to assess anti-inflammatory effects.
  • Investigated the impact of DSF+Cu2+ on CD4+ T cell-secreted interleukin 17 (IL-17) in DSS-induced TCRβ-/- mice.
  • Analyzed changes in intestinal flora using 16S rRNA sequencing and evaluated intestinal barrier function via tight junction protein expression.

Main Results:

  • DSF+Cu2+ significantly ameliorated UC symptoms, including weight loss, disease activity, and colon damage.
  • The treatment inhibited colonic macrophage activation by blocking the NF-κB pathway, reducing NLRP3-inflammasome activation and IL-1β secretion.
  • DSF+Cu2+ decreased IL-17 secretion by CD4+ T cells, protected the intestinal barrier by restoring tight junction proteins (ZO-1, occludin, MUC2), and improved gut microbiota balance.

Conclusions:

  • DSF+Cu2+ demonstrates significant therapeutic potential for ulcerative colitis by modulating immune responses and improving gut microbiota.
  • The combination therapy effectively reduces colonic inflammation and restores intestinal barrier integrity.
  • DSF+Cu2+ represents a promising novel therapeutic strategy for clinical application in treating UC.