PubMed · 4528395
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D H Brown, C T Gould, A Tatevossian. 1974. A robust pH electrode system for student use.. https://doi.org/10.1016/0003-9969(74)90079-x
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The standard treatment of human leishmaniases involves the use of pentavalent antimony [Sb(V)] compounds, including meglumine antimoniate. The mode of action of these compounds has not been fully elucidated. The possibility that Sb(III) is involved has been suggested; however, the biomolecule that may induce the conversion of Sb(V) to Sb(III) has not yet been identified. In the present study, we investigated both the ability of reduced glutathione (GSH) to promote the reduction of Sb(V) into Sb(III) in meglumine antimoniate and the effects of pH and temperature on this transformation. GSH did promote the reduction of Sb(V) into Sb(III) in a dose-dependent manner. When GSH and meglumine antimoniate were incubated together at a GSH/Sb molar ratio superior or equal to 5:1, all antimony was encountered in the reduced form, indicating a stoichiometry of 5:1 between GSH and Sb(V) in the reaction. The reaction between Sb(V) and GSH was favored at an acidic pH (pH 5) and an elevated temperature (37 degrees C), conditions found within the phagolysosome, in which Leishmania resides. For instance, about 30% of the Sb(V) (concentration, 2mM) was converted to Sb(III) following incubation for 3 days with 10 mM GSH at pH 5 and 37 degrees C. Our data support the hypothesis that Sb(V) would be converted by GSH, or a related thiol compound, to more toxic Sb(III) in the phagolysosome of macrophages.
Visceral leishmaniasis should be suspected in renal transplant recipients in whom a fever develops of unknown origin. A 53-year-old renal transplant recipient developed pyrexia, hepatosplenomegaly, and pancytopenia 4 years after transplantation. Antileishmaniasis serology was negative, and the diagnosis was confirmed through bone marrow examination. Treatment with glucantine (N-methylglucamine antimoniate) led to acute pancreatitis, and treatment with ketoconazole plus allopurinol for 21 days was effective to eradicate Leishmania donovani.
This manuscript describes the use of Supercritical-Fluid Chromatography (SFC) with plasma spectrometric detection for the analysis of organometallics. An introduction on the principles and characteristics of Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) is included, along with a discussion about requirements for coupling SFC to plasma detection and the different approaches for interfacing SFC to ICP. The last part of this review paper provides a comprehensive description of SFC-ICP applications for the analysis of organometallics containing iron, silicon, tin, chromium, arsenic, lead, mercury and antimony.