scholarly journals Sensitivity to a Metabolite of Diclofenac as a Cause of Acute Immune Hemolytic Anemia

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 407-413 ◽  
Author(s):  
D. Bougie ◽  
S.T. Johnson ◽  
L.A. Weitekamp ◽  
R.H. Aster
Keyword(s):  
Hemolytic Anemia ◽  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Proton Nuclear Magnetic Resonance ◽  
Glucuronide Conjugate ◽  
Negative Results ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Liquid Chromatographic

A 75-year-old woman taking the nonsteroidal anti-inflammatory drug diclofenac (DCF ) presented with acute Coombs-positive hemolytic anemia and subsequently developed renal failure. A drug-dependent antibody specific for red blood cells (RBCs) could not be demonstrated by in vitro testing with DCF. However, her serum was found to contain an IgM antibody that reacted strongly with RBCs in the presence of urine from any of four subjects who had ingested DCF. The active substance in urine was isolated, subjected to high-performance liquid chromatographic (HPLC) analysis, and found to be a glucuronide conjugate of a known DCF metabolite, 4′-hydroxydiclofenac (4′-OH DCF ). Negative results were obtained with four other DCF metabolites. Two 4′-OH DCF glucuronides were synthesized in vitro using a liver microsomal system. One promoted agglutination of normal RBCs by the patient's serum and was identified as the glucuronide ester of 4′-OH DCF by proton nuclear magnetic resonance (NMR) analysis. Studies with a panel of RBCs showed that the patient's antibody reacted preferentially with the e antigen of the Rh system. Acute immune hemolytic anemia in this patient appears to have been caused by sensitization to DCF modified by 4′ hydroxylation and glucuronidation. This is the first reported example of immune cytopenia caused by sensitivity to a glucuronide conjugate of a drug metabolite. Since glucuronidation is a common pathway of drug metabolism, studies of the frequency with which glucuronide derivatives of primary medications cause immune cytopenia seem warranted.

scholarly journals Sensitivity to a Metabolite of Diclofenac as a Cause of Acute Immune Hemolytic Anemia

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 407-413 ◽  
Author(s):  
D. Bougie ◽  
S.T. Johnson ◽  
L.A. Weitekamp ◽  
R.H. Aster
Keyword(s):  
Hemolytic Anemia ◽  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Proton Nuclear Magnetic Resonance ◽  
Glucuronide Conjugate ◽  
Negative Results ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Liquid Chromatographic

Abstract A 75-year-old woman taking the nonsteroidal anti-inflammatory drug diclofenac (DCF ) presented with acute Coombs-positive hemolytic anemia and subsequently developed renal failure. A drug-dependent antibody specific for red blood cells (RBCs) could not be demonstrated by in vitro testing with DCF. However, her serum was found to contain an IgM antibody that reacted strongly with RBCs in the presence of urine from any of four subjects who had ingested DCF. The active substance in urine was isolated, subjected to high-performance liquid chromatographic (HPLC) analysis, and found to be a glucuronide conjugate of a known DCF metabolite, 4′-hydroxydiclofenac (4′-OH DCF ). Negative results were obtained with four other DCF metabolites. Two 4′-OH DCF glucuronides were synthesized in vitro using a liver microsomal system. One promoted agglutination of normal RBCs by the patient's serum and was identified as the glucuronide ester of 4′-OH DCF by proton nuclear magnetic resonance (NMR) analysis. Studies with a panel of RBCs showed that the patient's antibody reacted preferentially with the e antigen of the Rh system. Acute immune hemolytic anemia in this patient appears to have been caused by sensitization to DCF modified by 4′ hydroxylation and glucuronidation. This is the first reported example of immune cytopenia caused by sensitivity to a glucuronide conjugate of a drug metabolite. Since glucuronidation is a common pathway of drug metabolism, studies of the frequency with which glucuronide derivatives of primary medications cause immune cytopenia seem warranted.

scholarly journals Inhibition of prolyl oligopeptidase by flavonoids isolated from the roots of Allexis obanensis (Baker f.) Melch

2021 ◽  
Vol 1 (2) ◽  
pp. 39-44
Author(s):  
Olivier Ndogo Eteme ◽  
Nkwengoua Tchouboun Zondegoumba Ernestine ◽  
Soh Desire ◽  
Oladimeji Taiwo Babatunde ◽  
Barthelemy Nyasse
Keyword(s):  
Neurodegenerative Diseases ◽  
Column Chromatography ◽  
Inhibitory Activity ◽  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Chromatographic Technique ◽  
Carboxy Terminus ◽  
Prolyl Oligopeptidase ◽  
Liquid Chromatographic

Background: Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyzes peptides containing proline at the carboxy terminus of proline residues. It has been associated with several neurodegenerative diseases. Therefore, it is a target in the management of these disease conditions. Methods: Allexis obanensis was taken through cold extraction, subjected to column chromatography and flavonoids isolated via high-performance liquid chromatographic technique. The flavonoids obtained were investigated for their in vitro prolyl oligopeptidase inhibitory activity. Results: The flavonoids isolated include: 4.4'''- dimethoxylophirone A [1] and 7-hydroxy-3-(3-hydroxy-4 méthoxyphenyl)-5- méthoxy-4H chromen-4-one [2]. They inhibited prolyl oligopeptidase at low IC50 concentrations of 7.201±3.021 µM and 6.223±2.002 µM respectively. Conclusion: The results obtained from this study proves the potential of these flavonoids as prolyl oligopeptidase inhibitors, by inference, their potentiality in the management of neuropsychiatric disorders.

scholarly journals Endogenous 1-H-Pyrrole-2,3,5-Tricarboxylic Acid (PTCA) in Hair and Its Forensic Applications: A Pilot Study on a Wide Multi-Ethnic Population

2020 ◽  
Author(s):  
Sara Casati ◽  
Ilaria Angeli ◽  
Alessandro Ravelli ◽  
Roberta F Bergamaschi ◽  
Andrea Guzzi ◽  
...  
Keyword(s):  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Tricarboxylic Acid ◽  
Ethnic Population ◽  
Hair Samples ◽  
Significant Difference ◽  
Endogenous Compound ◽  
Asian Pacific ◽  
Liquid Chromatographic

Abstracrt Over the years, several studies have shown that many factors are likely to affect the results of forensic hair analyses and complicate their interpretation. Among these factors, one of the major drawbacks in hair analysis is the affectability of deposited xenobiotics by cosmetic treatments, which could be eventually used to adulterate the sample. It is well known that some cosmetic treatments containing hydrogen peroxide, such as permanent dyeing or bleaching, lead to the formation of 1-H-pyrrole-2,3,5-tricarboxylic acid (PTCA), a melanin degradation product. Considering that PTCA is also an endogenous compound, spontaneously formed by natural oxidation of melanin, its only detection in hair is not enough to confirm a cosmetic oxidative treatment. For this reason, the aim of the present work was to develop and validate a reliable liquid–liquid extraction method in ultra-high-performance liquid chromatographic–tandem mass spectrometry for the determination of endogenous PTCA in hair from a wide multi-ethnic population (African, Arab, Asian-Pacific, Caucasian, Hispanic and Indian). According to previous studies, untreated hair samples showed a PTCA content of 8.54 ± 5.72 ng/mg (mean ± standard deviation [SD]), ranging between 0.44 and 23.7 ng/mg; after in vitro cosmetic bleaching, PTCA increased to 16.8 ± 6.95 ng/mg (range: 4.16–32.3 ng/mg). Comparing baseline PTCA levels of each subgroup with the others, we could not observe any statistically significant difference, except for Caucasians (P < 0.05), wherein the concentrations were lower. Further studies and a wider sampling are necessary to elucidate the role of PTCA as diagnostic marker of cosmetic hair treatment in forensic field.

scholarly journals HPLC analysis, antimicrobial and antioxidant activities of Daphne cneorum L.

2012 ◽  
Vol 66 (5) ◽  
pp. 709-716 ◽  
Author(s):  
Nedeljko Manojlovic ◽  
Pavle Maskovic ◽  
Perica Vasiljevic ◽  
Ratomir Jelic ◽  
Marina Juskovic ◽  
...  
Keyword(s):  
High Performance ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Total Phenolics ◽  
Antioxidant Activities ◽  
High Performance Liquid Chromatographic ◽  
Hplc Method ◽  
Potential Source ◽  
Liquid Chromatographic

The present study describes in vitro antimicrobial and antioxidant activities of the methanol extracts which were obtained from the leaves and twigs of the plant Daphne cneorum L. The antimicrobial activity of these extracts was tested against human pathogenic microorganisms using a minimum inhibitory concentration (MIC) values. Total phenolics and flavonoids, as well as the antioxidant activity of the extracts were determined. The two tested extracts showed good antimicrobial and antioxidant activities. The results of a high performance liquid chromatographic (HPLC) method showed that 7,8-dihydroxycoumarin is one of the most abundant secondary metabolite in the tested extracts. The results of this study clearly indicated that the extracts of D. cneorum could be used as a potential source of natural antioxidant and antimicrobial agents.

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