In Vivo Evaluation of Retinal Neurodegeneration in Patients with Multiple Sclerosis

To evaluate macular morphology in the eyes of patients with multiple sclerosis (MS) with or without optic neuritis (ON) in previous history.Optical coherence tomography (OCT) examination was performed in thirty-nine patients with MS and in thirty-three healthy subjects. The raw macular OCT data were processed using OCTRIMA software. The circumpapillary retinal nerve fiber layer (RNFL) thickness and the weighted mean thickness of the total retina and 6 intraretinal layers were obtained for each eye. The eyes of MS patients were divided into a group of 39 ON-affected eyes, and into a group of 34 eyes with no history of ON for the statistical analyses. Receiver operating characteristic (ROC) curves were constructed to determine which parameter can discriminate best between the non-affected group and controls.The circumpapillary RNFL thickness was significantly decreased in the non-affected eyes compared to controls group only in the temporal quadrant (p = 0.001) while it was decreased in the affected eyes of the MS patients in all quadrants compared to the non-affected eyes (p<0.05 in each comparison). The thickness of the total retina, RNFL, ganglion cell layer and inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, comprising the RNFL and GCL+IPL) in the macula was significantly decreased in the non-affected eyes compared to controls (p<0.05 for each comparison) and in the ON-affected eyes compared to the non-affected eyes (p<0.001 for each comparison). The largest area under the ROC curve (0.892) was obtained for the weighted mean thickness of the GCC. The EDSS score showed the strongest correlation with the GCL+IPL and GCC thickness (p = 0.007, r = 0.43 for both variables).Thinning of the inner retinal layers is present in eyes of MS patients regardless of previous ON. Macular OCT image segmentation might provide a better insight into the pathology of neuronal loss and could therefore play an important role in the diagnosis and follow-up of patients with MS

Optical Coherence Tomography in Parkinsonian Syndromes

BACKGROUND/OBJECTIVE: Parkinson's disease (PD) and the atypical parkinsonian syndromes multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are movement disorders associated with degeneration of the central nervous system. Degeneration of the retina has not been systematically compared in these diseases. METHODS: This cross-sectional study used spectral-domain optical coherence tomography with manual segmentation to measure the peripapillar nerve fiber layer, the macular thickness, and the thickness of all retinal layers in foveal scans of 40 patients with PD, 19 with MSA, 10 with CBS, 15 with PSP, and 35 age- and sex-matched controls. RESULTS: The mean paramacular thickness and volume were reduced in PSP while the mean RNFL did not differ significantly between groups. In PSP patients, the complex of retinal ganglion cell- and inner plexiform layer and the outer nuclear layer was reduced. In PD, the inner nuclear layer was thicker than in controls, MSA and PSP. Using the ratio between the outer nuclear layer and the outer plexiform layer with a cut-off at 3.1 and the additional constraint that the inner nuclear layer be under 46 µm, we were able to differentiate PSP from PD in our patient sample with a sensitivity of 96% and a specificity of 70%. CONCLUSION: Different parkinsonian syndromes are associated with distinct changes in retinal morphology. These findings may serve to facilitate the differential diagnosis of parkinsonian syndromes and give insight into the degenerative processes of patients with atypical parkinsonian syndromes

The Use of Computational Fluid Dynamics in the Design of a Pharmaceutical Processor

The use of solid oral dosage such as tablets accounts for approximately 60 % of the total frequency of all pharmaceutical dosage forms. In addition to this 90 % of all drugs supplied are in tablet form even if they are presented in other medicinal forms. During tablet production there are a number of processes that are carried out, in what is essentially a batch process. This work describes the use of computational fluid dynamics (CFD) in the design of a new single vessel pharmaceutical processor. Initially a simple model was developed using the computational code STAR-CD. The results of this were compared with tests carried out in a prototype processor. This provided confidence to develop the design. During the design phases of the work all potential design features have been modeled and the final design choices made on the basis of the CFD results. The initial phases of the work were carried out using single-phase models, however all the recent design work has been carried out using a two-phase flow model

The Use of Computational Fluid Dynamics in the Design of a Pharmaceutical Processor

The use of solid oral dosage such as tablets accounts for approximately 60 % of the total frequency of all pharmaceutical dosage forms. In addition to this 90 % of all drugs supplied are in tablet form even if they are presented in other medicinal forms. During tablet production there are a number of processes that are carried out, in what is essentially a batch process. This work describes the use of computational fluid dynamics (CFD) in the design of a new single vessel pharmaceutical processor. Initially a simple model was developed using the computational code STAR-CD. The results of this were compared with tests carried out in a prototype processor. This provided confidence to develop the design. During the design phases of the work all potential design features have been modeled and the final design choices made on the basis of the CFD results. The initial phases of the work were carried out using single-phase models, however all the recent design work has been carried out using a two-phase flow model

Crystal structures and kinetic studies of a laboratory evolved aldehyde reductase explain the dramatic shift of its new substrate specificity

Abstract The Fe²⁺-dependent E. coli enzyme FucO catalyzes the reversible interconversion of short-chain (S)-lactaldehyde and (S)-1,2-propane­diol, using NADH and NAD⁺ as cofactors, respectively. Laboratory-directed evolution experiments have been carried out previously using phenyl­acetaldehyde as the substrate for screening catalytic activity with bulky substrates, which are very poorly reduced by wild-type FucO. These experiments identified the N151G/L259V double mutant (dubbed DA1472) as the most active variant with this substrate via a two-step evolutionary pathway, in which each step consisted of one point mutation. Here the crystal structures of DA1472 and its parent D93 (L259V) are reported, showing that these amino acid substitutions provide more space in the active site, though they do not cause changes in the main-chain conformation. The catalytic activity of DA1472 with the physiological substrate (S)-lactaldehyde and a series of substituted phenyl­acetaldehyde derivatives were systematically quantified and compared with that of wild-type as well as with the corresponding point-mutation variants (N151G and L259V). There is a 9000-fold increase in activity, when expressed as kcat/KM values, for DA1472 compared with wild-type FucO for the phenyl­acetaldehyde substrate. The crystal structure of DA1472 complexed with a non-reactive analog of this substrate (3,4-di­meth­oxy­phenyl­acetamide) suggests the mode of binding of the bulky group of the new substrate. These combined structure–function studies therefore explain the dramatic increase in catalytic activity of the DA1472 variant for bulky aldehyde substrates. The structure comparisons also suggest why the active site in which Fe²⁺ is replaced by Zn²⁺is not able to support catalysis

Retinal nerve fibre layer loss in hereditary spastic paraplegias is restricted to complex phenotypes

<p>Abstract</p> <p>Background</p> <p>Reduction of retinal nerve fibre layer (RNFL) thickness was shown as part of the neurodegenerative process in a range of different neurodegenerative pathologies including Alzheimer′s disease (AD), idiopathic Parkinson’s disease (PD), spinocerebellar ataxia (SCA) and multiple system atrophy (MSA). To further clarify the specificity of RNFL thinning as a potential marker of neurodegenerative diseases we investigated RNFL thickness in Hereditary Spastic Paraplegia (HSP), an axonal, length-dependent neurodegenerative pathology of the upper motor neurons.</p> <p>Methods</p> <p>Spectral domain optical coherence tomography (OCT) was performed in 28 HSP patients (clinically: pure HSP = 22, complicated HSP = 6; genetic subtypes: SPG4 = 13, SPG5 = 1, SPG7 = 3, genetically unclassified: 11) to quantify peripapillary RNFL thickness. Standardized examination assessed duration of disease, dependency on assistive walking aids and severity of symptoms quantified with Spastic Paraplegia Rating Scale (SPRS).</p> <p>Results</p> <p>HSP patients demonstrated no significant thinning of global RNFL (<it>p</it>_global = 0.61). Subgroup analysis revealed significant reduction in temporal and temporal inferior sectors for patients with complex (p<0.05) but not pure HSP phenotypes. Two of three SPG7-patients showed severe temporal and temporal inferior RNFL loss. Disease duration, age and severity of symptoms were not significantly correlated with global RNFL thickness.</p> <p>Conclusion</p> <p>Clinically pure HSP patients feature no significant reduction in RNFL, whereas complex phenotypes display an abnormal thinning of temporal and temporal inferior RNFL. Our data indicate that RNFL thinning does not occur unspecifically in all neurodegenerative diseases but is in HSP restricted to subtypes with multisystemic degeneration.</p