β-Glucan attenuates TLR2- and TLR4-mediated cytokine production by microglia

Microglia, the resident immune cells of the brain, are activated in response to any kind of CNS injury, and their activation is critical for maintaining homeostasis within the CNS. However, during inflammatory conditions, sustained microglial activation results in damage to surrounding neuronal cells. β-Glucans are widely recognized immunomodulators, but the molecular mechanisms underlying their immunomodulatory actions have not been fully explored. We previously reported that β-glucans activate microglia through Dectin-1 without inducing significant amount of cytokines and chemokines. Here, we show that particulate β-glucans attenuate cytokine production in response to TLR stimulation; this inhibitory activity of β-glucan is mediated by Dectin-1 and does not require particle internalization. At the molecular level, β-glucan suppressed TLR-mediated NF-κB activation, which may be responsible for the diminished capacity of microglia to produce cytokines in response to TLR stimulation. Overall, these results suggest that β-glucans may be used to prevent or treat excessive microglial activation during chronic inflammatory conditions.     

A Regional Blood Flow Model for ��2-Microglobulin Kinetics and for Simulating Intra-dialytic Exercise Effect

A kinetic model based on first principles, for β(2)-microglobulin, is presented to obtain precise parameter estimates for individual patient. To reduce the model complexity, the number of model parameters was reduced using a priori identifiability analysis. The model validity was confirmed with the clinical data of ten renal patients on post-dilution hemodiafiltration. The model fit resulted in toxin distribution volume (V(d)) of 14.22 ± 0.75 L, plasma fraction in extracellular compartment (f(P)) of 0.39 ± 0.03, and inter-compartmental clearance of 44 ± 4.1 mL min(-1). Parameter estimates suggest that V(d) and f(P) are much higher in hemodialysis patients than in normal subjects. The developed model predicts larger removed toxin mass than that predicted by the two-pool model. On the application front, the developed model was employed to explain the effect of intra-dialytic exercise on toxin removal. The presented simulations suggest that intra-dialytic exercise not only increases the blood flow to low flow region, but also decreases the inter-compartmental resistance. Combined, they lead to increased toxin removal during dialysis and reduced post-dialysis rebound. The developed model can assist in suggesting the improved dialysis dose based on β(2)-microglobulin, and also lead to quantitative inclusion of intra-dialytic exercise in the future.     

Drosophila Nora virus capsid proteins differ from those of other picorna-like viruses

The recently discovered Nora virus from Drosophila melanogaster is a single-stranded RNA virus. Its published genomic sequence encodes a typical picorna-like cassette of replicative enzymes, but no capsid proteins similar to those in other picorna-like viruses. We have now done additional sequencing at the termini of the viral genome, extending it by 455 nucleotides at the 5' end, but no more coding sequence was found. The completeness of the final 12,333-nucleotide sequence was verified by the production of infectious virus from the cloned genome. To identify the capsid proteins, we purified Nora virus particles and analyzed their proteins by mass spectrometry. Our results show that the capsid is built from three major proteins, VP4A, B and C, encoded in the fourth open reading frame of the viral genome. The viral particles also contain traces of a protein from the third open reading frame, VP3. VP4A and B are not closely related to other picorna-like virus capsid proteins in sequence, but may form similar jelly roll folds. VP4C differs from the others and is predicted to have an essentially α-helical conformation. In a related virus, identified from EST database sequences from Nasonia parasitoid wasps, VP4C is encoded in a separate open reading frame, separated from VP4A and B by a frame-shift. This opens a possibility that VP4C is produced in non-equimolar quantities. Altogether, our results suggest that the Nora virus capsid has a different protein organization compared to the order Picornavirales.     

Patient motion correction for multiplanar, multi-breath-hold cardiac cine MR imaging

PURPOSE: To correct for spatial misregistration of multi-breath-hold short-axis (SA), two-chamber (2CH), and four-chamber (4CH) cine cardiac MR (CMR) images caused by respiratory and patient motion. MATERIALS AND METHODS: Twenty CMR studies from consecutive patients with separate breath-hold 2CH, 4CH, and SA 20-phase cine images were considered. We automatically registered the 2CH, 4CH, and SA images in three dimensions by minimizing the cost function derived from plane intersections for all cine phases. The automatic alignment was compared with manual alignment by two observers. RESULTS: The processing time for the proposed method was <20 seconds, compared to 14-24 minutes for the manual correction. The initial plane displacement identified by the observers was 2.8 +/- 1.8 mm (maximum = 14 mm). A displacement of >/=5 mm was identified in 15 of 20 studies. The registration accuracy (defined as the difference between the automatic parameters and those obtained by visual registration) was 1.0 +/- 0.9 mm, 1.1 +/- 1.0 mm, 1.1 +/- 1.2 mm, and 2.0 +/- 1.8 mm for 2CH-4CH alignment and SA alignment in the mid, basal, and apical regions, respectively. The algorithm variability was higher in the apex (2.0 +/- 1.9 mm) than in the mid (1.4 +/- 1.4 mm) or basal (1.2 +/- 1.2 mm) regions (ANOVA, P < 0.05). CONCLUSION: An automated preprocessing algorithm can reduce spatial misregistration between multiple CMR images acquired at different breath-holds and plane orientations.     

Mammary gland homeostasis employs serotonergic regulation of epithelial tight junctions

Homeostatic control of volume within the alveolar spaces of the mammary gland has been proposed to involve a feedback system mediated by serotonin signaling. In this article, we describe some of the mechanisms underlying this feedback based on studies of a human normal mammary epithelial cell line (MCF10A) and mouse mammary epithelium. Mammary serotonin was elevated during lactation and after injection of 5-hydroxytryptophan (5-HTP). The genes encoding the serotonin reuptake transporter (SERT) and the type 7 serotonin receptor (5-HT(7)) were expressed in human and mouse mammary epithelial cells, and serotonin caused a concentration-dependent increase of cAMP in MCF10A cells. Mouse and human mammary epithelial cells formed polarized membranes, in which tight junction activity was monitored. Treatment of mammary epithelial membranes with serotonin receptor antagonists increased their transepithelial electrical resistance (TEER). Antagonist and agonist effects on TEER were mediated by receptors on the basolateral face of the membranes. Our results suggest a process in which serotonin accumulates in the interstitial fluid surrounding the mammary secretory epithelium and is detected by 5-HT(7) receptors, whereupon milk secretion is inhibited. One mechanism responsible for this process is serotonin-mediated opening of tight junctions, which dissipates the transepithelial gradients necessary for milk secretion.     

Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride

One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present investigation ultradeformable lipid vesicles, that is, elastic liposomes were prepared incorporating propranolol hydrochloride for enhanced transdermal delivery. Elastic liposomes bearing propranolol hydrochloride were prepared by conventional rotary evaporation method and characterized for various parameters including vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux, enhancement ratio (ER), and release pattern of propranolol hydrochloride were calculated for transdermal delivery. In vivo study conducted on male albino rats (Sprague Dawley) was also taken as a measure of performance of elastic liposomal, liposomal, and plain drug solution. The better permeation through the skin was confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the elastic liposomal formulation for transdermal delivery of propranolol hydrochloride provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared to liposomes.     

Unilateral proptosis and extradural hematoma in a child with scurvy

We report a 3-year-old boy with unilateral proptosis, painful swelling of the right thigh and aphasia. He had radiographic evidence of scurvy in the limbs and bilateral frontal extradural hematomas with a mass lesion in the left orbit on MRI. He was treated with vitamin C and on follow-up 8 weeks later had recovered with no evidence of the orbital mass on clinical or radiological study. Scurvy manifesting as proptosis and extradural hematoma is rare.     

Gastrectomy case volume and textbook outcome: an analysis of the Population Registry of Esophageal and Stomach Tumours of Ontario (PRESTO)

Gastric Cancer - To determine the association between gastric cancer surgery case-volume and Textbook Outcome, a new composite quality measurement. Textbook Outcome&nbsp;included (a) negative...     

Osteogenic markers in peri-implant crevicular fluid in immediate and delayed-loaded dental implants: A randomized controlled trial

Introduction

The study evaluates the levels of matrix metalloprotease-8 (MMP-8), and Cathepsin-K (CatK) in peri-implant crevicular fluid (PICF) among patients with immediate loaded (IL) and delayed-loaded (DL) implants at different time points to know the inflammation and osteogenic status.

Methods

The study population consisted of two groups (n = 25, each group) with a mean age of 28.7 ± 3.5 years, and PICF was collected. MMP-8 and CatK levels were quantified through ELISA.

Results

We observed the concentrations of inflammatory markers (MMP-8 and CatK) at three time points in the IL and DL groups. The mean concentration of MMP-8 in the IL group was 9468 ± 1230 pg/mL, 5547 ± 1088 pg/mL, and 7248 ± 1396 pg/mL at 2 weeks, 3 months, and 12 months, respectively; while in the DL group was 10 816 ± 779.7 pg/mL, 9531 ± 1245 pg/mL, and 9132 ± 1265 pg/mL at 2 weeks, 3 and 12 months, respectively. The mean concentration of Cat-K in the IL group was observed at 422.1 ± 36.46 pg/mL, 242.9 ± 25.87 pg/mL, and 469 ± 75.38 pg/mL at 2 weeks, 3, and 12 months, whereas in the DL group was 654.6 ± 152.9 pg/mL, 314.7 ± 28.29 pg/mL, and 539.8 ± 115.1 pg/mL at 2 weeks, 3 months and 12 months, respectively.

Conclusion

In this study, the levels of CatK and MMP-8 levels decline at 12 months in both groups, and the IL group shows lower values compared to the DL group; however, no significant changes were observed after analyses were adjusted for multiple comparisons (p > 0.025). Therefore, there is not much difference observed in the inflammation process between immediate and delayed loading. (Clinical trial identifier: CTRI/2017/09/009668).