Alteration of serum thymus and activation‐regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti‐interleukin‐17A agents

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side‐effects of biologics, dose‐reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation‐regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI‐clear with biologics than in the group which did not achieve PASI‐clear. Among biologics, the group treated with secukinumab, an anti‐interleukin (IL)‐17A agent, showed significantly higher TARC level compared with the group treated with anti‐tumor necrosis factor agents. In certain populations achieving PASI‐clear, serum TARC level may be a potent marker reflecting better response to IL‐17A inhibitors, and in this case step down of treatment for psoriasis is possible.     

Prosaposin regulates coenzyme Q10 levels in HepG2 cells,especially those in mitochondria

Coenzyme Q10 (CoQ10) is a key component of the mitochondrial electron transfer chain and is one of the most important cellular antioxidants. We previously reported that glycoprotein saposin B (SapB) binds CoQ10 in human cells. To elucidate the physiological role of SapB and its precursor, prosaposin (Psap), we prepared stable transfectants of HepG2 that overexpress wild-type human Psap (Wt-Tf). We also established a SapB domain mutated Psap (Mt-Tf) in which cysteine¹⁹⁸ was replaced with serine to disrupt three dimensional protein structure by the loss of S-S bridging. Psap knockdown (KD) strains were also examined. Western blotting analysis confirmed overexpression or knockdown of Psap in these HepG2 cells. The cellular ratios of CoQ10 to free cholesterol (FC) significantly decreased in the order of Wt-Tf>parental>Mt-Tf>KD. Additionally, the ratios of CoQ10/FC in mitochondrial fractions decreased in the order of Wt-Tf>parental>KD. These data indicate that Psap and/or SapB regulate CoQ10 levels in HepG2 cells, especially in their mitochondria.     

Predictors of early vs. late permanent shunt insertion after aneurysmal subarachnoid hemorrhage

Objective: Numerous studies have identified different predictors for secondary hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH), although predictors regarding timing of the shunt operation have never been reported. Predictors for an early shunt, which was defined as a shunt operation performed ≤30 days after SAH onset, and for a late shunt, performed at >40 days, were investigated.

Methods: A total of 735 consecutive SAH patients admitted to our hospital between 2003 and 2014 who underwent surgery for ruptured aneurysms within five days of onset were retrospectively assessed.

Results: Secondary hydrocephalus developed in 225 patients, including 70 with an early shunt and 96 with a late shunt. Multivariate analysis showed that predictors for secondary hydrocephalus were age ≥70 years, World Federation of Neurosurgical Society (WFNS) grade IV-V, Fisher grade 3–4, intraventricular hemorrhage, anterior cerebral artery aneurysms, and external drainage for acute hydrocephalus (p < 0.05). In the early and late shunt groups, multivariate analysis indicated that early shunt was significantly associated with coil embolization, and late shunt was correlated with middle cerebral artery aneurysms and cerebral infarction due to vasospasm (p < 0.05).

Discussion: The difference in the predictors between the early and late shunts implied that the mechanisms of secondary hydrocephalus differed between the early and late shunt groups. Knowledge of the associated risk factors might help to predict the timing of the shunt operation for early rehabilitation planning in the future.     

Sphingomyelin changes in rat cerebral cortex during focal ischemia

Abstract

To better define the sphingolipid metabolism during focal brain ischemia, levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by occlusion of the middle cerebral artery. Sphingomyelin began to decrease at 2 hours of ischemia and continued to decrease for 96 hours. In contrast, ceramide increased at 6 hours and increased to 4.2-fold at 96 hours after ischemia, and the fatty acid composition of ceramide was solely nonhydroxylated fatty acid similar to sphingomyelin. Hydroxylated fatty acid-linked cerebroside decreased at 6 hours of ischemia, whereas any significant decrease of nonhydroxylated fatty acid-linked cerebroside didn't occur for 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. These results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during early ischemia. [Neurol Res 1996; 18: 337-341]