Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Tratamiento y manejo fibrinolítico en síndrome de Nicolau: Caso clínico / Fibrinolytic treatment and management in Nicolau syndrome: Clinical case

RESUMEN Introducción: El síndrome de Nicolau (SN), conocido como embolia cutis medicamentosa o dermatitis livedoide es un acontecimiento adverso debido a la administración de inyecciones intramusculares, intraarteriales, subcutánea e incluso intraarticulares asociado a diversos fármacos1. Se desconoce toda la patogenia de este síndrome, pero se ha asociado a lesión vascular, trombosis arterial, espasmo reflejo de las arterias, oclusión vascular por microembolia e inflamación. Caso clínico: Paciente masculino de 32 años de edad, luego de inyección intramuscular de penicilina benzatínica presenta dolor intenso en área de inyección que se acompaña de lesiones eritematosas a nivel de abdomen, escroto y miembro inferior derecho además de presentar dolor, pareste-sia, palidez moteado eritematoso (livedo) y disminución de pulsos en dicha extremidad por lo que se diagnostica isquemia aguda (IA) que requirió tratamien-to fibrinolitico, entre otros fármacos. Conclusión: El síndrome de Nicolau es una condición iatrogénica que puede ser producida por inyección de múltiples medicamentos, puede presentar diferentes síntomas y signos como lesión neurológica, necrosis en área de irrigación de vasos afectados e incluso isquemia aguda. En este caso el manejo con rt-PA fue efectivo en tratar la isquemia. El conocimiento de este síndrome y sus complicaciones facilitaría su manejo2.Palabras claves: Síndrome Nicolau, bencilpenicilina, anticoagulante, rt-PA

ABSTRACT Introduction: Nicolau syndrome (NS), known as cutaneous embolism or livedoid dermatitis, is an adverse event due to the administration of intramuscular, intraarterial, subcutaneous and intraarticular injections associated with various drugs1. The entire pathogenesis of this syndrome is unknown, but it has been associated with vascular injury, arterial thrombosis, reflex spasm of the arteries, vascular occlusion due to microemboli, and inflammation. Clinical case: 32-year-old male. After an intramuscular injection of benzathine penicillin, the patient presented severe pain in the injection area accompanied by erythem-atous lesions at the level of the abdomen, scrotum, and right lower limb. In addition to that, the patient presented pain, paresthesia, and mottled paleness erythema (livedo). Moreover, the patient had a decreased pulse in the right limb, acute ischemia was diagnosed and required fibrinolitic treatment, among other drugs. Conclusion: Nicolau Syndrome, is an iatrogenic condition that is produced by injection of multiple drugs. It can produce different symptoms and signs from neurological injury, necrosis in the irrigation area of affected vessels and acute ischemia. rt-PA management in this case was effective in treating ischemia. It is essential to know about this syndrome and its complications. This would facilitate its management2.Keywords: Nicolau syndrome, benzylpenicillin, anticoagulant, rt-PA.

Preparation of impurity C in benzathine benzylpenicillin products / 中国药学杂志

OBJECTIVE: To prepare impurity C in benzathine benzylpenicillin products. METHODS: Using the mother liquor of benzathine benzylpenicillin, impurity C was prepared by means of vacuum distillation, column chromatography, and recrystallization. Its molecular structure was confirmed with UV, IR, MS, NMR and elemental analysis. Its purity and correction factor were determined by HPLC method. The contents of impurity C in the samples were determined by external standard method. RESULTS: The prepared product was proved to be impurity C by structure confirmation. CONCLUSION: The preparation of impurity C in benzathine benzylpenicillin products has important significance for the control of related substances of benzathine benzylpenicillin products.