THP-2

An Epstein-Barr virus-negative lymphoma cell line, THP-2, was established from a Burkitt's lymphoma taken from a Japanese patient. THP-2 cells grew in single cell suspension with a doubling time of 24 hr; the cells carried surface-bound mu-lambda immunoglobulins and formed rosettes with IgG antibody-coated ox erythrocytes. THP-2 cells expressed B1, common acute lymphoblastic leukemia (ALL) (J5) and Ia-like antigens of their surface as defined by monoclonal antibodies. Epstein-Barr virus-associated nuclear antigen (EBNA) was not detected. The cell line THP-2 has been maintained for over 5 years. Among the markers examined, only common ALL antigen has been present on the cell surface of THP-2 for these 5 years.

The phosphane Cu(I) complex [Cu(thp)4][PF6], 1 (thp=tris(hydroxymethyl)phosphane) shows notable in vitro antitumour activity against a wide range of solid tumours. Uptake experiments performed in 1-treated colon cancer cells by atomic absorption spectrometry, reveal that the antiproliferative activity is consistent with the intracellular copper content. The solution chemistry of this agent, investigated by means of X-ray Absorption Spectroscopy and spectrophotometric titrations in aqueous media, indicates that 1 is labile giving coordinative unsaturated [Cu(thp)n]+ species (n=3 and 2) at micromolar concentrations. [Cu(thp)n]+ are reactive species that yield the mixed-ligand complex [Cu(thp)2(BCS)]- (BCS: bathocuproinedisulphonate(2-)) upon interaction with N,N-diimine. Analogously, [Cu(thp)n]+ interact with the methionine-rich peptide sequence (Ac-MMMMPMTFK-NH2; Pep1), relevant in the recruiting of physiological copper, giving [Cu(thp)(Pep1)]+ and [Cu(Pep1)]+ species. The formation of these adducts was assessed by electrospray mass spectrometry in the positive ion mode and validated by density functional theory investigations. The possibility to trans-chelate Cu(I) from pure inorganic [Cu(thp)n]+ assemblies into more physiological adducts represents a pathway that complex 1 might follow during the internalization process into cancer cells.

(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP (n = 25), and benztropine (n = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues.