RepoMed (Medizinische Hochschule Hannover)
Not a member yet
3024 research outputs found
Sort by
Synaptophysin presents a reliable marker to detect axonal damage in animal models of multiple sclerosis
Get PDFInzidenzen und Risikofaktoranalyse für Wundinfektionen nach endoprothetischem Kniegelenksersatz
Get PDFIdentification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis
No full textEnteroviruses are among the most common causes of viral meningitis. Enteroviral
meningitis continues to represent diagnostic challenges, as cerebrospinal fluid
(CSF) cell numbers (a well validated diagnostic screening tool) may be normal in
up to 15% of patients. We aimed to identify potential CSF biomarkers for
enteroviral meningitis, particularly for cases with normal CSF cell count. Using
targeted liquid chromatography-mass spectrometry, we determined metabolite
profiles from patients with enteroviral meningitis (n = 10), and subdivided them
into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts.
Non-inflamed CSF samples from patients with Bell's palsy and normal pressure
hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed
considerable metabolic reprogramming in the meningitis samples. It identified
phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC,
0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a
perfect biomarker for enteroviral meningitis with an increased CSF cell count
(AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC,
0.87) biomarker for enteroviral meningitis with normal cell count, and a combined
classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly
perfect classification (AUC, 0.99). Taken together, this analysis reveals the
potential of CSF metabolites as additional diagnostic tools for enteroviral
meningitis, and likely other Central nervous system (CNS) infection
Force, impulse and energy during falling with and without knee protection: an in-vitro study
No full textThe mechanics of protective knee padding mitigating injury from a high-force fall
have not been investigated in real-life scenarios to date. This study compares
the effect of wearing knee pads to unprotected impact on a hard surface. We
hypothesized that knee pads reduce the force and energy transmitted to the bony
structures of the knee cap compared with unprotected conditions. Eight human knee
cadaver specimens were embedded and fixed with a flexion angle of 100 degrees in
a custom-made drop testing device (75 kg including the knee). The usage of a knee
pad led to an average peak force attenuation on impact of 15% (no pad: 5932 N SD:
2472 N; pad: 4210 N SD: 2199 N; p < 0.001). Contact time on the plate was higher
with a knee pad (no pad: 0.015 s SD: 0.009 s; pad: 0.028 s SD: 0.014 s; p <
0.001). Therefore, the observed impulse was also increased (no pad: 62.2 Ns SD:
17.8 Ns; pad: 74.6 Ns SD: 18.6 Ns; p < 0.001). This effect diminished as drop
height was increased. Energy dissipation, defined as the difference between
kinetic energy pre-impact and peak potential energy post-impact, was higher
without a knee pad (no pad: 10.5 J SD: 6.2 J; pad: 4.2 J SD: 5.0 J; p < 0.001).
The results from this study illustrate the magnitude of influence that knee pads
have on peak forces, transmitted impulse, and energy transfer from a high-force
impact in real-life scenarios. Contrary to expectations, the knee pad did not act
as a mechanical damper. The mechanical behavior more closely resembled a spring
that temporarily stores energy and consequentially reduces peak forces upon
impact. Based on this study, future developments in padding might benefit from
focusing on the aspect of energy storage and temporarily delayed energy
dissipatio
A European study on decellularized homografts for pulmonary valve replacement: initial results from the prospective ESPOIR Trial and ESPOIR Registry data
No full textOBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date. METHODS: Prospective European multicentre trial evaluating DPH for pulmonary valve replacement. Matched comparison of DPH to bovine jugular vein (BJV) conduits and cryopreserved homografts (CH) considering patient age, type of heart defect and previous procedures. RESULTS: In total, 121 patients (59 female) were prospectively enrolled (August 2014-December 2016), age 21.3 +/- 14.4 years, DPH diameter 24.4 +/- 2.8 mm. No adverse events occurred with respect to surgical handling; there were 2 early deaths (30 + 59 years) due to myocardial failure after multi-valve procedures and no late mortality (1.7% mortality). After a mean follow-up of 2.2 +/- 0.6 years, the primary efficacy end points mean peak gradient (16.1 +/- 12.1 mmHg) and regurgitation (mean 0.25 +/- 0.48, grade 0-3) were excellent. One reoperation was required for recurrent subvalvular stenosis caused by a pericardial patch and 1 balloon dilatation was performed on a previously stented LPA. 100% follow-up for DPH patients operated before or outside the trial (n = 114) included in the ESPOIR Registry, age 16.6 +/- 10.4 years, diameter 24.1 +/- 4.2 mm, follow-up 5.1 +/- 3.0 years. The combined DPH cohort, n = 235, comprising both Trial and Registry data showed significantly better freedom from explantation (DPH 96.7 +/- 2.1%, CH 84.4 +/- 3.2%, P = 0.029 and BJV 82.7 +/- 3.2%, P = 0.012) and less structural valve degeneration at 10 years when matched to CH, n = 235 and BJV, n = 235 (DPH 61.4 +/- 6.6%, CH 39.9 +/- 4.4%, n.s., BJV 47.5 +/- 4.5%, P = 0.029).CONCLUSIONS: Initial results of the prospective multicentre ESPOIR Trial showed DPH to be safe and efficient. Current DPH results including Registry data were superior to BJV and CH.Trial registration clinicaltrial
Expression, Localization and Functional Activity of the Major Na+/H+ Exchange Isoforms Expressed in the Intestinal Cell Line Caco-2BBe
No full textBACKGROUND/AIMS: Enterocytes express a number of NHE isoforms with presumed localization in the apical (NHE2, 3 and 8) or basolateral (NHE1) membrane. Functional activity and localization of enterocyte NHE isoforms were assessed using fully differentiated Caco-2BBe cells, whose genetic expression profile closely resembles mature enterocytes. METHODS: The activity of the different NHEs was analyzed by fluorometric pHi-metry in a perfusion chamber with separate apical and basolateral perfusion, using specific inhibitors and shRNA knockdown of NHE2. The expression of the NHEs and of other relevant acid extrusion transporters was quantified by qPCR. RESULTS: Quantitative comparison of the mRNA expression levels of the different NHE isoforms in 14 day-differentiated Caco-2BBe cells showed the following order: NHE2>NHE8>NHE3>NHE1. Acid-activated NHE exchange rates in the basolateral membrane were >6-fold higher than in the apical membrane. 79 +/- 3 % of the acid-activated basolateral Na(+)/H(+) exchange rate displayed a NHE1-typical inhibitor profile, and no NHE2/3/8 typical activity could be observed. Analysis of the apical Na(+)/H(+) exchange rates revealed that approximately 51 +/- 3 % of the total apical activity displayed a NHE2/8-typical inhibitor profile and 31 +/- 6 % a NHE3-typical inhibitor profile. Because no selective NHE2 inhibitor is available, a stable NHE2 knockdown cell line (C2NHE2KD) was generated. C2NHE2KD displayed a reduced NHE2-typical apical Na(+)/H(+) exchange rate and maintained a lower steady-state pHi, despite high expression levels of other acid extruders, in particular NBCn1 (Slc4a7). CONCLUSION: Differentiated Caco-2BBe cells display particularly high mRNA expression levels of NHE2, which can be functionally identified in the apical membrane. Although at low intracellular pH, NHE2 transport rate was far lower than that of NHE1. NHE2 activity was nevertheless essential for the maintenance of the steady-state pHi of these cell
Kaposi’s sarcoma-associated herpesvirus vIRF2 protein utilizes an IFN-dependent pathway to regulate viral early gene expression
No full textKaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) belongs to the subfamily of Gammaherpesvirinae and is the etiological agent of Kaposi's sarcoma as well as of two lymphoproliferative diseases: primary effusion lymphoma and multicentric Castleman disease. The KSHV life cycle is divided into a latent and a lytic phase and is highly regulated by viral immunomodulatory proteins which control the host antiviral immune response. Among them is a group of proteins with homology to cellular interferon regulatory factors, the viral interferon regulatory factors 1-4. The KSHV vIRFs are known as inhibitors of cellular interferon signaling and are involved in different oncogenic pathways. Here we characterized the role of the second vIRF protein, vIRF2, during the KSHV life cycle. We found the vIRF2 protein to be expressed in different KSHV positive cells with early lytic kinetics. Importantly, we observed that vIRF2 suppresses the expression of viral early lytic genes in both newly infected and reactivated persistently infected endothelial cells. This vIRF2-dependent regulation of the KSHV life cycle might involve the increased expression of cellular interferon-induced genes such as the IFIT proteins 1, 2 and 3, which antagonize the expression of early KSHV lytic proteins. Our findings suggest a model in which the viral protein vIRF2 allows KSHV to harness an IFN-dependent pathway to regulate KSHV early gene expression
Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection
No full textThe presence of B-cell clusters in allogenic T cell-mediated rejection (TCMR) of kidney allografts is linked to more severe disease entities. In this study we characterized B-cell infiltrates in patients with TCMR and examined the role of serum CXCL-13 in these patients and experimentally. CXCL-13 serum levels were analyzed in 73 kidney allograft recipients at the time of allograft biopsy. In addition, four patients were evaluated for CXCL13 levels during the first week after transplantation. ELISA was done to measure CXCL-13 serum levels. For further mechanistic understanding, a translational allogenic kidney transplant (ktx) mouse model for TCMR was studied in BalbC recipients of fully mismatched transplants with C57BL/6 donor kidneys. CXCL-13 serum levels were measured longitudinally, CD20 and CD3 composition and CXCL13 mRNA in tissue were examined by flow cytometry and kidneys were examined by histology and immunohistochemistry. We found significantly higher serum levels of the B-cell chemoattractant CXCL13 in patients with TCMR compared to controls and patients with borderline TCMR. Moreover, in patients with acute rejection within the first week after ktx, a >5-fold CXCL13 increase was measured and correlated with B-cell infiltrates in the biopsies. In line with the clinical findings, TCMR in mice correlated with increased systemic serum-CXCL13 levels. Moreover, renal allografts had significantly higher CXCL13 mRNA expression than isogenic controls and showed interstitial CD20+ B-cell clusters and CD3+ cell infiltrates accumulating in the vicinity of renal vessels. CXCL13 blood levels correlate with B-cell involvement in TCMR and might help to identify patients at risk of a more severe clinical course of rejection
