Region Of Capsule Research Articles

An in vivo study on brain microstructure in biological and chronological ageing.

This study aimed to investigate whether magnetization transfer imaging (MTI) parameters of cortical gray and white matter and subcortical gray matter structures differ between subjects enriched for human familial longevity and control subjects to provide a thorough description of the brain phenotype of familial longevity. Moreover, we aimed to describe cerebral ageing effects on MTI parameters in an elderly cohort. All subjects were included from the Leiden Longevity Study and underwent 3 Tesla MTI of the brain. In total, 183 offspring of nonagenarian siblings, who are enriched for familial factors of longevity, were contrasted with 163 environmentally and age-matched controls. No differences in cortical and subcortical gray matter and white matter MTI parameters were found between offspring and control subjects using histogram-based and voxel-wise analyses. Cortical gray matter and white matter MTI parameters decreased with increasing chronological age (all p < 0.001). Decrease of white matter magnetization transfer ratio (MTR) was homogeneous throughout the whole mean white matter skeleton except for parts of the callosal splenium and partly the posterior limb of the internal capsule and superior region of the corona radiata (p < 0.05). Mean MTR of subcortical gray matter structures decreased with increasing age (p amygdala, caudate nucleus and putamen < 0.001; p pallidum = 0.001, p thalamus = 0.002). In conclusion, the brain phenotype of human familial longevity is - at a mean age of 66 years - not characterized by preserved macromolecular brain tissue integrity.

The Clinicopathological Features of BRAF Mutated Papillary Thyroid Cancers in Chinese Patients.

The BRAFV600E mutation is commonly found in papillary thyroid cancers (PTCs) at different frequencies in different regions. However, the association between the BRAFV600E mutation and clinicopathological features in Chinese PTC patients is unknown. A total of 543 Chinese patients with histologically confirmed PTC were enrolled in this study. For the BRAF mutation assay, the target fragments were amplified and sequenced with an ABI 3500 gene analyzer. In 170 of 543 samples (31.3%), the BRAFV600E mutation was detected. In the bivariate analysis, the BRAFV600E mutation showed an association with bilaterality, tumor size, extrathyroidal invasion, and lymph node metastases (LNM). However, in the multivariate analysis, the BRAFV600E mutation was positively related to only tumor size (>1 cm) and extrathyroidal invasion. In addition, the multivariate analysis also showed that the age at diagnosis (<45 y) and tumor size (>1 cm) were independent predictors for LNM. In this study, the BRAFV600E mutation is positively associated with worse prognostic factors, including larger tumor size and the tumor extending to the thyroid capsule or extrathyroidal region; however, it is not an independent predictor for LNM.

Profile of collagen gene expression in the glenohumeral capsule of patients with traumatic anterior instability of the shoulder

ObjectiveTo evaluate the expression of the genes COL1A1, COL1A2, COL3A1 and COL5A1 in the glenohumeral capsule of patients with traumatic anterior instability of the shoulder. MethodsSamples from the glenohumeral capsule of 18 patients with traumatic anterior instability of the shoulder were evaluated. Male patients with a positive grip test and a Bankart lesion seen on magnetic resonance imaging were included. All the patients had suffered more than one episode of shoulder dislocation. Samples were collected from the injured glenohumeral capsule (anteroinferior region) and from the macroscopically unaffected region (anterosuperior region) of each patient. The expression of collagen genes was evaluated using the polymerase chain reaction after reverse transcription with quantitative analysis (qRT-PCR). ResultsThe expression of COL1A1, COL1A2 and COL3A1 did not differ between the two regions of the shoulder capsule. However, it was observed that the expression of COL5A1 was significantly lower in the anteroinferior region than in the anterosuperior region (median±interquartile range: 0.057±0.052 vs. 0.155±0.398; p=0.028) of the glenohumeral capsule. ConclusionThe affected region of the glenohumeral capsule in patients with shoulder instability presented reduced expression of COL5A1.

Destruction of White Matter Integrity in Patients With Mild Cognitive Impairment and Alzheimer Disease

BackgroundAccumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD).ObjectiveThe aim of this research was to study the microstructural...

Perfil de expressão de genes do colágeno na cápsula glenoumeral de pacientes com instabilidade traumática anterior do ombro

ObjectiveTo evaluate the expression of the genes COL1A1, COL1A2, COL3A1 and COL5A1 in the glenohumeral capsule of patients with traumatic anterior instability of the shoulder. MethodsSamples from the glenohumeral capsule of 18 patients with traumatic anterior instability of the shoulder were evaluated. Male patients with a positive grip test and a Bankart lesion seen on magnetic resonance imaging were included. All the patients had suffered more than one episode of shoulder dislocation. Samples were collected from the injured glenohumeral capsule (anteroinferior region) and from the macroscopically unaffected region (anterosuperior region) of each patient. The expression of collagen genes was evaluated using the polymerase chain reaction after reverse transcription with quantitative analysis (qRT-PCR). ResultsThe expression of COL1A1, COL1A2 and COL3A1 did not differ between the two regions of the shoulder capsule. However, it was observed that the expression of COL5A1 was significantly lower in the anteroinferior region than in the anterosuperior region (median ± interquartile range: 0.057 ± 0.052 vs. 0.155 ± 0.398; p = 0.028) of the glenohumeral capsule. ConclusionThe affected region of the glenohumeral capsule in patients with shoulder instability presented reduced expression of COL5A1.

In Vivo Cervical Facet Joint Capsule Deformation During Flexion–Extension

Nonrandomized controlled cohort. To characterize subaxial cervical facet joint kinematics and facet joint capsule (FJC) deformation during in vivo, dynamic flexion-extension. To assess the effect of single-level anterior arthrodesis on adjacent segment FJC deformation. The cervical facet joint has been identified as the most common source of neck pain, and it is thought to play a role in chronic neck pain related to whiplash injury. Our current knowledge of cervical facet joint kinematics is based on cadaveric mechanical testing. Fourteen asymptomatic controls and 9 C5-C6 arthrodesis patients performed full range of motion flexion-extension while biplane radiographs were collected at 30 Hz. A volumetric model-based tracking process determined 3-dimensional vertebral position with submillimeter accuracy. FJC fibers were modeled and grouped into anterior, lateral, posterior-lateral, posterior, and posterior-medial regions. FJC fiber deformations (total, shear, and compression-distraction) relative to the static position were determined for each cervical motion segment (C2-C3 through C6-C7) during flexion-extension. No significant differences in the rate of fiber deformation in flexion were identified among motion segments (P = 0.159); however, significant differences were observed among fiber regions (P < 0.001). Significant differences in the rate of fiber deformation in extension were identified among motion segments (P < 0.001) and among fiber regions (P = 0.001). The rate of FJC deformation in extension adjacent to the arthrodesis was 45% less than that in corresponding motion segments in control subjects (P = 0.001). In control subjects, FJC deformations are significantly different among vertebral levels and capsule regions when vertebrae are in an extended orientation. In a flexed orientation, FJC deformations are different only among capsule regions. Single-level anterior arthrodesis is associated with significantly less FJC deformation adjacent to the arthrodesis when the spine is in an extended orientation. 4.

Standardization of Laser Welding Parameters for Attachment of Thermocouple to Pressurized Capsule for On-Line Creep Rupture Studies

Thermocouples are widely used in reactor applications due to their reliable performance in the reactor operating conditions. It is intended to use thermocouples to detect the in-reactor creep rupture of pressurized capsules. Attachment of thermocouple to the gas region of a pressurized capsule is a challenging task since the joint should withstand the high temperature and the associated high pressure at that high temperature. SS316 sheathed K type thermocouple of overall diameter of 1 mm is used in this study. Laser welding has been successfully adopted for this application, and this paper discusses the challenges involved, and the standardization of laser welding parameters to obtain defect- free laser welds.

Increase of Pyramidal Tract Fractional Anisotropy on MRI after Stem Cell Transplantation in ALS Patients

Background and Purpose: Amyotrophic lateral sclerosis (ALS) is characterized by the selective death of motor neurons. Cortical neuron loss is associated with axonal degeneration along specific white matter tracts. Fractional anisotropy (FA) determined by Magnetic Resonance (MR) might detect integrity or changes in brain white matter pathways. This study was aimed to analyze pyramidal tract changes in ALS patients submitted to stem cell transplantation into the frontal motor cortices. Patients and Methods: Fourteen patients with definite ALS were included. After signing their informed consent, the patients underwent magnetic resonance imaging (MRI). The pyramidal tract (PT) from the corona radiata to medulla oblongata was evaluated by quantitative voxel-wise analysis, including FA and diffusion tensor tractography derived from MR diffusion tensor imaging (MR-DTI) at baseline and 6 months after CD 133+ stem cells transplantation into the frontal motor cortices. FA changes were analyzed with the Tract-Based Spatial Statistics software (FMRIB Software Library, Oxford University). Statistical analyzes among FA before and after stem cells transplantation were performed using the SPSS, v.17. Results: Improvement in FA was observed in the PT of the whole group when compared at baseline with 6 months after stem cell transplantation (p= 0.05). FA significative changes were observed in the PT at the corona radiata (p= 0.05) and internal capsule regions (p= 0.03). FA changes were observed in the PT at the mesencephalic and bulbar regions. However, they were not statistically significant. Conclusions: FA positive changes suggest recovery of the PT in ALS subjects after stem cells transplantation. These changes could possible be explained not only by cell replacement but also by modifications of the extracellular motor neuronal environment, through trophic and neuroprotective effects of stem cells.

Type I Collagen-Based Fibrous Capsule Enhances Integration of Tissue-Engineered Cartilage with Native Articular Cartilage

Successful integration of engineered constructs with host tissues is crucial for cartilage repair, yet achieving it remains challenging. A collagen I-based fibrous capsule characterized by increased cell density and decreased glycosaminoglycan deposition usually forms at the periphery of tissue-engineered cartilage. The current study aimed to evaluate the effects of a solid fibrous capsule on construct integration with native articular cartilage. To this end, capsule-containing (CC) and capsule-free (CF) constructs were grown by culturing chondrocyte-seeded scaffolds with insulin-like growth factor-1 and transforming growth factor-β1, respectively, in a wavy-walled bioreactor that imparts hydrodynamic forces for 4weeks. The ability of harvested constructs to integrate with native cartilage was determined using a cartilage explant model. Our results revealed that adhesive stress between native cartilage and the CC constructs was 57% higher than that in the CF group, potentially due to the absence of glycosaminoglycans and increased cell density in the capsule region and deposition of denser and thicker collagen fibrils at the integration site. The present work demonstrates that the fibrous capsule can effectively enhance early integration of engineered and native cartilage tissues and thus suggests the need to include the capsule as a variable in the development of cartilage tissue engineering strategies.

Atypical mature bone in the otosclerotic otic capsule as the differentiated zone of an invasive osseous neoplasm

Conclusion: A large proportion of the mature otic capsule bone in cases of otosclerosis lies in plaques in direct contiguity with active otosclerosis and, because it shows significant structural defects, it should be regarded as part of the otosclerotic process. These appearances support our previously described suggestion that otosclerosis is an invasive osseous neoplasm, the mature atypical bone representing differentiation of earlier-formed invasive neoplastic osseous tissue. Objectives: We sought structural features in differentiated bone within the otic capsules of cases of otosclerosis that might indicate a relation to the underlying disease process. Methods: Fifty temporal bones from 42 adult patients with otosclerosis were processed into stained histological sections and the appearance of the otic capsule was compared with that of the same tissue, processed in the same way, in 10 cases that did not show otosclerosis. Results: In the cochlear otic capsules of otosclerotic temporal bones, when traced back along the otosclerotic plaque from the invasive front, atypical shapes and arrangements of osteons were seen, often with otospongiosis (severe dilatation of multiple Volkmann's canals), culminating in larger differentiated osteons with irregularities in structure. In the medial region of the otosclerotic cochlear otic capsule, at a similar position to that where giant normal osteons are present in the normal temporal bone, differentiated, giant abnormal osteons were seen. In the otosclerotic vestibular otic capsule there were changes similar to those of the otosclerotic cochlea (apart from the giant osteons) and many osteons composed of clusters of atypical osteoblast-like cells around highly atypical Volkmann's canals.

Distribution of Mast Cells and Macrophages and Expression of Interleukin-6 in Periapical Cysts

IntroductionMast cells and macrophages are important components of the inflammatory infiltrate found in inflammatory periapical diseases. Several cytokines participate in the mechanisms of inflammation, tissue repair, and bone resorption associated with periapical cysts. The aim of the present study was to evaluate the distribution of mast cells and macrophages and the expression of interleukin-6 (IL-6) in periapical cysts. MethodsThirty periapical cysts were selected for the study, and clinical, demographic, and gross information from the cases was obtained from the laboratory records. Five-micrometer sections stained with hematoxylin-eosin were reviewed for analysis of the microscopic features of the cysts, and 3-μm sections on silanized slides were used for immunohistochemical reactions with anti-tryptase, anti-CD68, and anti–IL-6. ResultsThere was no statistically significant difference in the mean number of mast cells and macrophages when comparing superficial and deep regions of the fibrous capsule of the cysts. Mean number of mast cells on the superficial region of the fibrous capsule was higher in cysts showing intense superficial inflammation and exocytosis. Macrophages were more commonly found in areas showing IL-6 expression, and IL-6 was less expressed in deep regions of the fibrous capsule in cysts showing greater gross volume. ConclusionsThe results reinforced the participation of mast cells and macrophages in the pathogenesis of periapical cysts and suggested that IL-6 is not the major bone resorption mediator in larger periapical cysts.

ULTRASTRUCTURE OF THE KARYOSPHERE IN DARKLING BEETLES (TENEBRIONIDAE COLEOPTERA POLYPHAGA)

SUMMARY The fine structural organization of nuclei was studied in the developing oocytes of Blaps lethifera Marsh., B. mortisaga L. and Gnaptor spinimanus Pall. (Tenebrionidae Coleoptera Polyphaga). At the beginning of diplotene the nuclei contain primary fibrillar nucleoli and numerous electron dense globules dispersed all over the nucleus; loose chromosome material (lamp-brush chromosomes) is distributed all over the nucleus. With oocyte growth the chromosomes become spiral-shaped and assembled into a karyosphere. Nucleolus-like bodies (NLB) appear on the chromosomes and then move to the capsule region and outside its limits to the nuclear envelope. They are fibrillar and non-active in RNA synthesis (they do not incorporate 3H- uridine). Fibrous material of the capsule is represented by strands which consist of bundles of cross-striated filaments. The latter contact directly with the chromosomes in the karyosphere and with the surface of NLB. Fibrillar-granular microbodies are distributed along the stra...

High affinity nuclear and nongenomic estradiol binding sites in the human and mouse lens

Estrogen is reported to be protective against cataracts in women and animal models. Immunodetection methods have identified the classic estrogen receptors (ER), ERα and ERβ, in human lens epithelial cells and their RNAs have been detected in the rat and human lens. To verify that estrogen binding occurs in the lens, sensitive [125I]-17β-estradiol binding analyses were performed on subcellular lens fractions from women (ages 39–78 years). The presence of high affinity estradiol binding sites in the nuclear, cytoplasmic, and membrane fractions indicate the lens is able to respond to estrogens, even up to age 78, although fewer binding sites were detected in the postmenopausal women. Additionally, due to the importance of mouse models in estrogen action and lens research, lenses from intact female mice were also analyzed. Both the C57BL/6 and FVB/N mouse strains also possessed high affinity binding sites in all three lens fractions. Furthermore, transcripts for ERα, ERβ, and G protein-coupled estrogen receptor (GPER; previously called GPR30) that bind estradiol with high affinity were expressed in the human and mouse lenses. These data provide the first evidence of GPER expression in the lens. Its role, functions, and subcellular location are currently unknown, but a G-shift assay in the membrane fractions of human and mouse lenses did not show evidence that estradiol induced classic G protein-coupled receptor activation. All three receptor transcripts were also detected in the lens capsule region isolated from female C57BL/6 mice, which is mainly comprised of epithelial cells. In contrast, only ERα and GPER were expressed in the cortex/nuclear region, which is primarily composed of differentiating and organelle-free fiber cells. No significant differences in specific estradiol binding and receptor RNA expression were observed in the lenses between male and female C57BL/6 mice. These findings indicate that the lens is an estrogen target tissue in both sexes. The identification of GPER, in addition to ERα and ERβ, in the lens also adds to the complexity of possible estrogen responses in the lens. Accordingly, the protective effects of estrogen in women and animals may be mediated by all three estrogen receptors in the lens. In addition, the similarities in binding and receptor RNA expression in the lenses of both species suggest that mice can be used to model estrogen action in the human lens.

Developmental Anatomy in the Zonular Connection with Lens Capsule in Macaque Eye

Morphological analyses of zonule conjugated with lens capsule were performed on the developmental change in eyes from the age of fetus to 7 years old of the rhesus macaques (Macaca fuscata). The zonule was filamentous network in late fetus. After birth, the zonular microfibrils originated from the nonpigmented epithelium of the ciliary process. On the extending path toward the lens capsule through the chamber, microfibril assembled with neighbor fibril and also cohered with one another forming bundle. With growth, these bundles bifurcated into anterior and posterior groups on the equatorial region of capsule. The developmental distribution of bundles in the capsule was characteristic on anterior group, that is, bifurcation into radial and circumferential extension. On the other hand, the posterior bundle undivided but radially extended within short distance from the equator. In the process of fixating with capsule, bundles untangled into fibrils and penetrated circumferentially into the superficial layer and radially into deep apical layer of the capsule. Zonule was composed fibrillin 1 microfibrils and on the extending path toward the lens capsule through the chamber, microfibril self-assembled with neighbored fibril in composition of fascicle and also cohered with one another forming bundle. Each bundle had alternating pale and dense horizontal bands in the intracapsular extension and the stripe pattern changed in flaccid or extensive tension of zonule between capsule and process. Zonular fibril intermingled with collagen fibril of capsule with interlacing molecule of laminin. At the base of ciliary muscle, elastin-positive connective tissue intercalated circumferentially between ciliary processes. The developmental changes of the intralamellar distribution and extension of zonule with striped pattern informed the functional role upon the elasticity in coordination with the lens capsule micromolecules.

Defining the molecular tumor margin regions of clear cell renal carcinoma tissues by MALDI-MS imaging of lipid and glycan species.

421 Background: The frequent tumor recurrence associated with clear cell renal cell carcinoma (ccRCC) suggests that there are underlying molecular processes present in the remaining tissue following nephrectomy that are not identified through conventional histopathological techniques. At the molecular level, transcript, metabolomic, and protein expression patterns have indicated a striking Warburg Effect profile in ccRCC tissues, with major affects on sugar and lipid metabolism. Our group has been applying MALDI mass spectrometry imaging approaches to uniquely profile lipids and glycans associated with disease progression directly in frozen tissue slides. Methods: Frozen ccRCC tissues with tumor, non-tumor adjacent, and tumor margin regions were selected by a pathologist. Lipid profiles from fresh-frozen tissue slides coated in DHB matrix were obtained on a dual source Bruker Solarix 70 FTICR mass spectrometer. Glycans were imaged in a similar fashion in ethanol-washed tissues using on-tissue protein N glycanase F digestion to release surface N-glycans. Detected lipid and glycan ion intensities were converted to a color pixel scale for creating an image of individual peaks, linked directly to the histopathology of the tissue. Results: Five groups of lipid and N-glycan species were identified following MALDI tissue imaging, those present in the immediate margin area of non-tumor tissue adjacent to tumor; only in non-tumor regions; only in tumor regions; primarily in tumor regions but extended beyond the margin; and present throughout the tissue. Specific lipid and glycan species associated with margin and tumor regions are being correlated with disease progression and pathology data. Conclusions: Analysis of the periphery of the tumor tissue and the normal parenchyma or capsule regions at this biomolecule level may better define the metastatic potential of the tumor as compared to analysis of the central tumor region. This approach has the potential to not only improve prognostic assessment and treatment choices, but also to inform on the underlying biology of ccRCC metastasis and new rational targets for therapeutic intervention.

Occurrence of parasitic copepods in Carangid fishes from Parangipettai, Southeast coast of India.

In the present study, 68 fishes were infested out of 544 specimens examined from six different species of Carangid fishes which were collected from Parangipettai coastal waters. Eight species of parasitic copepods were found on gill filaments, body surface and nasal capsule regions. The maximum prevalence was recorded in Carangoides malabaricus (22.5%) and minimum was noticed in (2.4%) Selaroides leptolepis. The intensity of infection ranged from 1 to 1.2. Thus, considerable variation in the respiratory area was observed owing to the attachment of parasites in the infected fishes. Caligus sp. and C. epidemicus parasites were attached to body surface and only one Sphyriid sp. parasites were found in nasal capsule region. It is very difficult to estimate the actual harm to fish caused by the presence of parasites; if this is uneasy in cultured fish, it is almost impossible in feral fish populations. It should also be emphasized that the presence of a parasite does not necessarily imply manifestation of a disease. In aquaculture, some parasites are able to reproduce rapidly and heavily infect a large proportion of fish which may lead to diseases with significant economic consequences.

Capsule function following anterior dislocation: Implications for diagnosis of shoulder instability

During shoulder dislocation, the glenohumeral capsule undergoes non-recoverable strain, leading to joint instability. Clinicians use physical exams to diagnose injury and direct repair procedures; however, they are subjective and do not provide quantitative information. Our objectives were to: (1) determine the relationship between capsule function following anterior dislocation and non-recoverable strain; and (2) identify joint positions at which physical exams can be used to detect non-recoverable strain in specific capsule regions. Physical exams were simulated at three joint positions including external rotation (ER) using robotic technology before and after anterior dislocation. The resulting joint kinematics, strain distribution in the capsule, and non-recoverable strain were determined. Following dislocation, anterior translation increased by as much as 48% (0° ER: p = 0.03; 30° ER: p = 0.03; 60° ER: p < 0.01). Capsule sub-regions with less non-recoverable strain required more ER to detect differences in the strain ratios between the intact and injured joint. Strain ratio changes on the humeral side of the posterior axillary pouch (0.31 ± 0.32) were significant at all joint positions (0° ER: p = 0.03; 30° ER: p = 0.048; 60° ER: p = 0.04), whereas strain ratio differences on the humeral side of the anterior axillary pouch (0.18 ± 0.21) were significant only at 60° of ER (p = 0.03). Therefore, standardizing physical exams for joint position could help surgeons identify specific locations of non-recoverable strain that may have been ignored.

Neuropsychiatric Symptoms as a Putative Crescendo Warning of a Striatocapsular Infarct?

Neuropsychiatric Symptoms as a Putative Crescendo Warning of a Striatocapsular Infarct?

Biodistribution of the Recombinant Fusion Protein Linking the Human Factor IX to Human Albumin (rIX-FP) in Rats

AbstractAbstract 1117The recombinant fusion protein linking the human coagulation factor IX to human albumin, rIX-FP, developed by CSL Behring GmbH, is currently undergoing investigation in clinical phase II/III trials (PROLONG - 9FP) for prophylaxis and on-demand treatment of bleeding in haemophilia B patients.The present study has been conducted to evaluate the biodistribution of rIX-FP in comparison to the marketed recombinant factor IX product BeneFIX®. Therefore, [3H]-rIX-FP or [3H]-BeneFIX®, labeled at lysine or terminal NH2 residues using the N-Succinimidyl [2,3,-3H] propionate (NSP) method, were administered intravenously to male Sprague Dawley (SD) rats at a single dose leading to a radioactive dose of 400 μCi/kg. Using whole-body autoradiography (QWBA), tissue radioactivity was determined at 0.25, 1, 3, 8, 24, 72, 120 and 240 hours following [3H]-rIX-FP, and at 0.25, 1, 3 and 24 hours following [3H]-BeneFIX® administration. In addition to full body sections, the hind limbs were separately subjected to QWBA to obtain more detailed information on the product distribution within the bone marrow, articular capsule and synovial region of the knee joints. In parallel, plasma, urine and faeces were collected at pre-dose and at several sampling points throughout the 24 and 240 hour study period, respectively, to calculate excretion balance and assess physiological elimination pathways. The radioactivity associated with the purified [3H]-labelled protein was determined by quantitative radiochemical analysis (QRA) and high performance liquid chromatography (HPLC). Biological activity of [3H]-labelled rIX-FP and BeneFIX® was confirmed using a chromogenic assay for factor IX activity. The radioactivity associated with plasma, urine and faeces samples was determined by QRA. HPLC-mass spectrometry (MS) techniques were employed to further characterize individual components identified following profiling of plasma and urine samples by size exclusion chromatography (SEC).Overall, the tissue distribution of [3H]-rIX-FP and [3H]-BeneFIX® was comparable, both penetrating predominantly into well perfused tissues and organs. Both products are also rapidly present in synovial and mineralized regions of knee joint sections and seem to mostly localize to the zone of calcified cartilage within the growth plate regions of long bones. For both, the longest retention time was observed in the bone marrow and endosteum of long bones. However, whereas [3H]-rIX-FP was detectable over 120 hours after administration, [3H]-BeneFIX® signal could only be detected until 24 hours post dosing. This is also reflected in the pharmacokinetic parameters determined based on the QRA of plasma and urine samples which suggested a terminal half life of 20.4 and 6.1 hours for [3H]-rIX-FP and [3H]-BeneFIX®, respectively, following correction for total radioactivity attributable to intact product. For both proteins, the major route of elimination was urinary. In case of [3H]-rIX-FP 73% of radioactivity was recovered in urine at 240 hours, the latest sampling point investigated. Less than 5% of radioactivity was eliminated in faeces and approximately 20% of radioactivity was present in tissues after 240 hours. Plasma profiling showed that up to 8 hours, 100% of the radioactivity could be assigned to unchanged [3H]-rIX-FP. From 24 to 240 hours, increasing levels of low molecular weight components (LMW) could be observed in plasma. Intriguingly, no high molecular protein components like [3H]-rIX-FP or albumin were detected in urine. Only LMW [3H]-components were found to be renally excreted. Such LMW components could be either be free [3H]-Lysine or bigger peptide fragments derived from [3H]-rIX-FP, which occur as a result of physiological protein catabolism. An exact identification of such renally excreted fragments is currently underway using HPLC-MS. Overall, the observed data are consistent with the hypothesis, that recycling via FcRn receptor is likely to be the physiological retention route for [3H]-rIX-FP.Consequently, this study shows that rIX-FP exhibits equal biodistribution compared to other marketed recombinant factor IX products such as BeneFIX®, but clearly distinguishes itself from BeneFIX® by its extended plasma half-life allowing a reduction in dosing frequency leading to increased therapeutic convenience and compliance. Disclosures:Herzog:CSL Behring GmbH: Employment. Harris:Quotient Bioresearch Metabolic Chemistry: Commercial Research Organisation Other. McEwen:Quotient Bioresearch Metabolic Chemistry: Commercial Research Organisation Other. Pragst:CSL Behring GmbH: Employment. Dickneite:CSl Behring GmbH: Employment. Schulte:CSL Behring GmbH: Employment. Zollner:CSL Behring GmbH: Employment.

The (Eigen)value of diffusion tensor imaging to investigate depression after traumatic brain injury

Many people with a traumatic brain injury (TBI), even mild to moderate, will develop major depression (MD). Recent studies of patients with MD suggest reduced fractional anisotropy (FA) in dorsolateral prefrontal cortex (DLPFC), temporal lobe tracts, midline, and capsule regions. Some of these pathways have also been found to have reduced FA in patients with TBI. It is unknown whether the pathways implicated in MD after TBI are similar to those with MD without TBI. This study sought to investigate whether there were specific pathways unique to TBI patients who develop MD. A sample of TBI-MD subjects (N = 14), TBI-no-MD subjects (N = 12), MD-no-TBI (N = 26), and control subjects (no TBI or MD, N = 23), using a strict measurement protocol underwent psychiatric assessments and diffusion tensor brain Magnetic Resonance Imaging (MRI). The findings of this study indicate that (1) TBI patients who develop MD have reduced axial diffusivity in DLPFC, corpus callosum (CC), and nucleus accumbens white matter tracts compared to TBI patients who do not develop MD and (2) MD patients without a history of TBI have reduced FA along the CC. We also found that more severe MD relates to altered radial diffusivity. These findings suggest that compromise to specific white matter pathways, including both axonal and myelination aspects, after a mild TBI underlie the susceptibility of these patients developing MD.