ABSTRACT
Deoxynojirimycin (DNJ) based imino sugars display antiviral activity in the tissue culture surrogate model of Hepatitis C (HCV), bovine viral diarrhoea virus (BVDV), mediated by inhibition of ER α-glucosidases. Here, the antiviral activities of neoglycoconjugates derived from deoxynojirimycin, and a novel compound derived from deoxygalactonojirimycin, by click chemistry with functionalised adamantanes are presented. Their antiviral potency, in terms of both viral infectivity and virion secretion, with respect to their effect on α-glucosidase inhibition, are reported. The distinct correlation between the ability of long alkyl chain derivatives to inhibit ER α-glucosidases and their anti-viral effect is demonstrated. Increasing alkyl linker length between DNJ and triazole groups increases α-glucosidase inhibition and reduces the production of viral progeny RNA and the maturation of the envelope polypeptide. Disruption to viral glycoprotein processing, with increased glucosylation on BVDV E2 species, is representative of α-glucosidase inhibition, whilst derivatives with longer alkyl linkers also show a further decrease in infectivity of secreted virions, an effect proposed to be distinct from α-glucosidase inhibition.
Subject(s)
Antiviral Agents/chemistry , Enzyme Inhibitors/chemistry , Glycoside Hydrolase Inhibitors , Imino Sugars/chemistry , 1-Deoxynojirimycin/chemistry , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Cattle , Cell Survival/drug effects , Click Chemistry , Diarrhea Viruses, Bovine Viral/metabolism , Dogs , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Glucosamine/analogs & derivatives , Glucosamine/chemistry , Glycosylation , Hepacivirus/metabolism , Imino Sugars/chemical synthesis , Imino Sugars/pharmacology , Madin Darby Canine Kidney Cells , Viral Envelope Proteins/metabolism , Virus Replication/drug effects , alpha-Glucosidases/metabolismABSTRACT
STUDY DESIGN: Group comparison and cross-sectional study. OBJECTIVES: To replicate previous findings regarding electroencephalographic (EEG) pattern differences in a larger sample of patients with spinal cord injury (SCI) and chronic pain than previously studied, and examine associations between pain severity and EEG activity in a sample of patients with SCI and chronic pain. SETTING: USA. METHODS: EEG data were collected in an eyes-closed condition from 38 individuals with SCI and chronic pain, 16 individuals with SCI who did not have chronic pain and 28 healthy controls. Pain intensity experienced during the EEG assessment was assessed in the chronic pain group. Absolute and relative power in four frequency bands (delta, theta, alpha, and beta) were compared between the groups, and correlation coefficients between bandwidth activity and pain intensity in the pain group were computed. RESULTS: Previously identified activity pattern differences (that is, more theta and less alpha) in those with SCI and chronic pain versus individuals with SCI and no pain and healthy controls were largely replicated. However, few significant associations between pain severity and EEG activity measures activity were found, and those that were found (more alpha activity associated with more pain as measured from frontal electrode sites) was in a direction opposite than predicted. CONCLUSION: The findings indicate that certain EEG activity patterns may be associated with more pain or a vulnerability to experience chronic pain in persons with SCI. Research examining the extent to which changes in this EEG activity may result in pain relief is warranted.
Subject(s)
Brain/physiopathology , Chronic Pain/etiology , Chronic Pain/physiopathology , Electroencephalography , Spinal Cord Injuries/complications , Spinal Cord Injuries/physiopathology , Adult , Aged , Aged, 80 and over , Analysis of Variance , Cross-Sectional Studies , Data Interpretation, Statistical , Female , Humans , Male , Middle Aged , Neuralgia/etiology , Neuralgia/physiopathology , Pain MeasurementABSTRACT
This study examined the effect of single versus triple-wrap cerclage fixation techniques in preventing propagation of a longitudinal fracture around a cementless femoral prosthesis. A proximal filling femoral component was implanted in 14 matched pairs of fresh-frozen bovine femora, following placement of a 45-mm longitudinal crack in the anteromedial cortical wall of the proximal femur. In one group of seven pairs, a single cerclage wire was applied to one specimen of each pair. A triple-wrap of a single cerclage wire was similarly placed in one specimen of each of the other seven pairs. All specimens were axially loaded on a materials testing system machine and the force required to propagate the fracture of the proximal femur was recorded. A triple-wrap cerclage technique required a significant increase in the force to propagate a proximal femur fracture around a non-cemented prosthesis when compared to a single cerclage wire.
