Synergistic interaction of fluconazole/sodium bicarbonate on the inhibition of Candida glabrata phospholipase gene

Abstract Candida glabrata infections are responsible for deaths of people globally. Fluconazole is known to be less effective against C. glabrata, which developed many strategies to evade being destroyed by fluconazole. To achieve enhanced efficacy of fluconazole against C. glabrata, the interaction of fluconazole with sodium bicarbonate was investigated using the CLSI guidelines. The efficacy of fluconazole alone and in combination with sodium bicarbonate was evaluated using the time-kill and phospholipase production assays. Eventually, the expression of PLB was assessed using semi-quantitative RT-PCR to investigate the inhibitory properties of fluconazole alone and in combination with sodium bicarbonate against C. glabrata. The fluconazole/sodium bicarbonate combination displayed synergistic and antagonistic effects (FICI= 0.375-4.25). In C. glabrata ATCC, SN 152, and SN 164, the fluconazole/sodium bicarbonate combination exhibited a significant fungicidal activity (p< 0.05) but antagonistic effect in the case of SN 283. With exception of SN 283, a significant reduction was noted in phospholipase production in clinical isolates of C. glabrata treated with fluconazole/sodium bicarbonate combination. The PLB was down-regulated significantly by 0.168-0.515 fold in C. glabrata treated with fluconazole/sodium bicarbonate. The results suggested fluconazole/sodium bicarbonate to have a potential synergistic interaction in C. glabrata, and the underlying mechanism may be associated with phospholipase gene

Interleukin-1beta promotes the expression of monocyte chemoattractant protein-1 in human aorta smooth muscle cells via multiple signaling pathways

Monocyte chemoattractant protein-1 (MCP1) plays a key role in monocyte/macrophage infiltration to the sub-endothelial space of the blood vessel wall, which is a critical initial step in atherosclerosis. In this study, we examined the intracellular signaling pathway of IL-1beta-induced MCP1 expression using various chemical inhibitors. The pretreatment of a phosphatidylcholine (PC)-specific PLC (PC-PLC) inhibitor (D609), PKC inhibitors, or an NF-kappaB inhibitor completely suppressed the IL-1beta-induced MCP1 expression through blocking NF-kappaB translocation to the nucleus. Pretreatment with inhibitors of tyrosine kinase or PLD partially suppressed MCP1 expression and failed to block nuclear NF-kappaB translocation. These results suggest that IL-1beta induces MCP1 expression through activation of NF-kappaB via the PC-PLC/PKC signaling pathway.

A case of amiodarone and neuromyopathy

La amiodarona es utilizada frecuentemente en el control de las arritmias cardíacas a pesar de sus múltiples efectos colaterales. Se reporta el caso de un varón de 38 años con diagnóstico de taquicardia ventricular que después de un año de uso crónico de amiodarona, presentó fatiga muscular, parestesias y temblor fino fistal en extremidades. Un aumento en la dosis de amiodarona por recidiva de la arritmia fue seguido de una elevación sostenida de los niveles séricos de la fracción MM de creatín fosfocinasa. Una electromiografia reveló neuropatía periférica sensitivo-motora, y una biopsia del cuadriceps, atrofia muscular de tipo neuropático, que se correlacionó con la presencia de depósitos intralisosomales e importante degeneración axonal en el nervio sural. Ambas alteraciones fueron dosis/tiempo dependiente. El caso ilustra la conveniencia de investigar intencionadamente estas alteraciones en pacientes que reciben este fármaco por periodos prolongados