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Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis
Christian ？stergaard, Stephen L Leib, Ian Rowland, Christian T Brandt
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-1
Abstract: Using an adult rat pneumococcal meningitis model, the impact of bacteremia accompanying meningitis on the development of hippocampal injury was studied. The study comprised of the three groups: I. Meningitis (n = 11), II. meningitis with attenuated bacteremia resulting from iv injection of serotype-specific pneumococcal antibodies (n = 14), and III. uninfected controls (n = 6).Pneumococcal meningitis resulted in a significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected controls (0.02 (0.00-0.02), Mann Whitney test, P = 0.0003). Also, meningitis with an attenuation of bacteremia by antibody treatment resulted in significantly reduced apoptosis (0.08 (0.02-0.20), P = 0.01) as compared to meningitis.Our results demonstrate that bacteremia accompanying meningitis plays an important role in the development of hippocampal injury in pneumococcal meningitis.Bacteremia and systemic complications are frequently associated with pneumococcal meningitis and, in approximately half of all fatal cases, are judged to be the primary causes of death [1,2]. Experimental pneumococcal meningitis studies have shown that accompanying bacteremia not only influenced mortality [3], but also the meningeal inflammatory response [4], cerebral autoregulation [5], and both ventricle size and brain edema [6]. Apoptosis in the dentate gyrus of hippocampus is an important histopathological finding in patients dying from bacterial meningitis [7], and in experimental meningitis, hippocampal apoptosis has been associated with the development of learning deficits (for a review see [8]). Both the invading pathogen [9] and host immune reactions [10,11] contributed to hippocampal injury during bacterial meningitis. Whilst it has been observed that systemically introduced pneumococci induced apoptosis in a non-meningitis sepsis model [12], the role of accompanying bacteremia on hippocampal apoptosis still remains to be defined in bacterial meningitis. Consequently, we investigated the ro
Brivaracetam as adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy: the current evidence base
Christian Brandt,Christian G. Bien,Theodor W. May
- , 2016, DOI: 10.1177/1756285616665564
Abstract: Brivaracetam (BRV) is a novel antiepileptic drug recently licensed for the treatment of partial epilepsy in adults and adolescents over 16 years old. Like levetiracetam (LEV), it is a ligand of the synaptic vesicle protein SV2A. BRV has been shown in animal models and in studies using human brain slices to have a higher SV2A affinity and faster penetration into the brain. Its efficacy and safety have been shown in several randomized, controlled studies. The recommended initial dose is 50–100 mg, divided into two daily doses. Up-titration to a 200 mg daily dose is possible. Dizziness and somnolence are frequent side effects. There are some hints that BRV may be less frequently associated with behavioural adverse events than LEV. Long-term efficacy and safety and BRV use in special patient groups have to be assessed in the future
Analysis of Respiratory Sounds: State of the Art
Sandra Reichert, Raymond Gass, Christian Brandt, Emmanuel Andrès
Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine , 2012,
Abstract: Objective: This paper describes state of the art, scientific publications and ongoing research related to the methods of analysis of respiratory sounds. Methods and material: Review of the current medical and technological literature using Pubmed and personal experience. Results: The study includes a description of the various techniques that are being used to collect auscultation sounds, a physical description of known pathologic sounds for which automatic detection tools were developed. Modern tools are based on artificial intelligence and on technics such as artificial neural networks, fuzzy systems, and genetic algorithms… Conclusion: The next step will consist in finding new markers so as to increase the efficiency of decision aid algorithms and tools.
Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation
Sander Dirk,Weimar Christian,Bramlage Peter,Brandt Tobias
BMC Neurology , 2012, DOI: 10.1186/1471-2377-12-102
Abstract: Background Patients in neurologic in-patient rehabilitation are at risk of cardio- and cerebrovascular events. Microalbuminuria (MAU) is frequent and an important risk predictor but has not been validated in in-patient rehabilitation. We therefore aimed to examine MAU as an indicator of risk and predictor of vascular events in a prospective study. Methods The INSIGHT (INvestigation of patients with ischemic Stroke In neuroloGic reHabiliTation) registry is the first to provide large scale data on 1,167 patients with acute stroke (< 3 months) that survived the initial phase of high risk and were undergoing neurologic in-patient rehabilitation. MAU was determined by dipstick-testing and correlated to baseline clinical variables (stroke-origin, functional impairment, co-morbidity, ankle-brachial-index, intima-media-thickeness) as well as vascular events after one year of follow-up. Comparisons were made with the χ2 or Mann–Whitney-U Test. Relative risks (RR) with 95% confidence intervals (CI) were estimated using log-binominal models. To evaluate the association between MAU and new vascular events as well as mortality, we calculated hazard ratios (HR) using Cox proportional hazard regression. Results A substantial proportion of patients was MAU positive at baseline (33.1%). Upon univariate analysis these patients were about 4 years older (69 vs. 65 years; p < 0.0001), had a slightly higher body mass index (27.8 vs. 27.1 kg/m2; p = 0.03) and increased waist circumference (79.5 vs. 50.4% for women [p < 0.0001] and 46.8 vs. 43.2% for men [p = 0.04]) and twice as often had diabetes mellitus (41.8 vs. 20.1%; p < 0.0001). Patients with MAU had a similar NIH stroke scale score (median 3 vs. 3; p = 0.379) but had lower values on the Barthel Index (median 75 vs. 90; p < 0.001). They had higher rates of atrial fibrillation (RR 1.38; 95% CI 1.09-1.75), coronary artery disease (RR 1.54; 95% CI 1.18-2.00), heart failure (RR 1.70; 95% CI 1.10-2.60) symptomatic peripheral artery disease (RR 2.30; 95% CI 1.40-3.80) and atherosclerotic stroke etiology (53.7 vs. 35.4%; p < 0.0001). MAU was associated with an increased intima-media-thickness, decreased ankle-brachial-index and polyvascular disease (RR 1.56; 95%CI 1.31-1.99). The event rate after a median follow-up of 13 months was 6.7% for fatal or nonfatal stroke, 4.7% for death, and 10.9% for combined vascular events (stroke, MI, vascular death). The presence of MAU was predictive for vascular events during the following year (HR for total mortality 2.2; 95% CI 1.3-3.7; HR for cardiovascular events 2.3; 95% 1.2 - 4
Results From Core-Collapse Simulations with Multi-Dimensional, Multi-Angle Neutrino Transport
Timothy D. Brandt,Adam Burrows,Christian D. Ott,Eli Livne
Physics , 2010, DOI: 10.1088/0004-637X/728/1/8
Abstract: We present new results from the only 2D multi-group, multi-angle calculations of core-collapse supernova evolution. The first set of results from these calculations was published in Ott et al. (2008). We have followed a nonrotating and a rapidly rotating 20 solar mass model for ~400 ms after bounce. We show that the radiation fields vary much less with angle than the matter quantities in the region of net neutrino heating. This obtains because most neutrinos are emitted from inner radiative regions and because the specific intensity is an integral over sources from many angles at depth. The latter effect can only be captured by multi-angle transport. We then compute the phase relationship between dipolar oscillations in the shock radius and in matter and radiation quantities throughout the postshock region. We demonstrate a connection between variations in neutrino flux and the hydrodynamical shock oscillations, and use a variant of the Rayleigh test to estimate the detectability of these neutrino fluctuations in IceCube and Super-K. Neglecting flavor oscillations, fluctuations in our nonrotating model would be detectable to ~10 kpc in IceCube, and a detailed power spectrum could be measured out to ~5 kpc. These distances are considerably lower in our rapidly rotating model or with significant flavor oscillations. Finally, we measure the impact of rapid rotation on detectable neutrino signals. Our rapidly rotating model has strong, species-dependent asymmetries in both its peak neutrino flux and its light curves. The peak flux and decline rate show pole-equator ratios of up to ~3 and ~2, respectively.
Influence of the blood bacterial load on the meningeal inflammatory response in Streptococcus pneumoniae meningitis
Christian ？stergaard, Terence O'Reilly, Christian Brandt, Niels Frimodt-M？ller, Jens D Lundgren
BMC Infectious Diseases , 2006, DOI: 10.1186/1471-2334-6-78
Abstract: To explore the role of systemic infection on the meningeal inflammation, experimental meningitis was induced by intracisternal injection of ~1 × 106 CFU Streptococcus pneumoniae, type 3, and the 26 rabbits were either provided with ~1 × 106 CFU S. pneumoniae intravenously at 0 hour ("bacteraemic" rabbits, n = 9), immunized with paraformaldehyde-killed S. pneumoniae for 5 weeks prior to the experiment ("immunized" rabbits", n = 8), or not treated further ("control" rabbits, n = 9). WBC and bacterial concentrations were determined in CSF and blood every second hour during a 16 hours study period together with CSF IL-8 and protein levels. We also studied CSF and blood WBC levels in 153 pneumococcal meningitis patients with and without presence of bacteraemia.As designed, blood bacterial concentrations were significantly different among three experimental groups during the 16 hours study period (Kruskal Wallis test, P < 0.05), whereas no differences in CSF bacterial levels were observed (P > 0.05). Blood WBC decreased in bacteraemic rabbits between ~10–16 hours after the bacterial inoculation in contrast to an increase for both the immunized rabbits and controls (P < 0.05). The CSF pleocytosis was attenuated in bacteraemic rabbits as compared to the two other groups between 12–16 hours from time of infection (P < 0.017), despite accelerated CSF IL-8 levels in bacteraemic rabbits.In patients with pneumococcal meningitis, no significant difference in CSF WBC was observed between patients with or without bacteraemia at admission (n = 103, 1740 cells/μL (123–4032) vs. n = 50, 1961 cells/μL (673–5182), respectively, P = 0.18), but there was a significant correlation between CSF and blood WBC (n = 127, Spearman rho = 0.234, P = 0.008).Our results suggest that a decrease in peripheral WBC induced by enhanced bacteraemia in pneumococcal meningitis results in an attenuated CSF pleocytosis.Streptococcus pneumoniae meningitis is characterized by an accumulation of leukocytes withi
Plasma and Muscle Myostatin in Relation to Type 2 Diabetes
Claus Brandt, Anders R. Nielsen, Christian P. Fischer, Jakob Hansen, Bente K. Pedersen, Peter Plomgaard
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037236
Abstract: Objective Myostatin is a secreted growth factor expressed in skeletal muscle tissue, which negatively regulates skeletal muscle mass. Recent animal studies suggest a role for myostatin in insulin resistance. We evaluated the possible metabolic role of myostatin in patients with type 2 diabetes and healthy controls. Design 76 patients with type 2 diabetes and 92 control subjects were included in the study. They were matched for age, gender and BMI. Plasma samples and biopsies from the vastus lateralis muscle were obtained to assess plasma myostatin and expression of myostatin in skeletal muscle. Results Patients with type 2 diabetes had higher fasting glucose (8.9 versus 5.1 mmol/L, P<0.001), plasma insulin (68.2 versus 47.2 pmol/L, P<0.002) and HOMA2-IR (1.6 versus 0.9, P<0.0001) when compared to controls. Patients with type 2 diabetes had 1.4 (P<0.01) higher levels of muscle myostatin mRNA content than the control subjects. Plasma myostatin concentrations did not differ between patients with type 2 diabetes and controls. In healthy controls, muscle myostatin mRNA correlated with HOMA2-IR (r = 0.30, P<0.01), plasma IL-6 (r = 0.34, P<0.05) and VO2 max (r = ？0.26, P<0.05), however, no correlations were observed in patients with type 2 diabetes. Conclusions This study supports the idea that myostatin may have a negative effect on metabolism. However, the metabolic effect of myostatin appears to be overruled by other factors in patients with type 2 diabetes.
Differences in the Detoxification Metabolism between Two clonal Lineages of the Aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) Reared on Tobacco (Nicotiana tabacum L.)
Cabrera-Brandt,Marco A; Fuentes-Contreras,Eduardo; Figueroa,Christian C;
Chilean journal of agricultural research , 2010, DOI: 10.4067/S0718-58392010000400006
Abstract: myzus persicae (sulzer) is a highly polyphagous aphid species, with a subspecies (m. persicae nicotianae) well adapted to tobacco (nicotiana tabacum l.). we evaluated the effect of this host plant on the aphid performance and detoxification enzymes, in order to test the participation of xenobiotic metabolism on the ability of this aphid to overcome the tobacco chemical defences. two genotypes, one corresponding to the only m. persicae nicotianae genotype reported in chile on tobacco, and one genotype belonging to m. persicae sensu stricto were reared on tobacco and pepper (capsicum annuum l.), respectively. m. persicae nicotianae showed a significantly higher intrinsic rate of increase (rm) on pepper than on tobacco, and m. persicae s.s. performed similarly, but with no reproduction at all on tobacco. in order to evaluate the effect of tobacco on detoxification enzymes, esterases, glutathione s-transferases (gst) and cytochrome p-450 monooxygenases (mo) were determined in both selected aphid genotypes after 12, 24, 36, 48 and 72 h of rearing on tobacco and pepper. m. persicae nicotianae exhibited the higher total esterase activities when reared on tobacco than on pepper after 48 h of rearing, while the activities of gst and mo did not show any significant difference between host-plants and duration of treatment. for m. persicae s.s., no significant differences were observed among host-plants for the studied enzymes. these results suggest a participation of the esterases, on the ability of this m. persicae nicotianae to overcome the tobacco defences.
Differences in the Detoxification Metabolism between Two clonal Lineages of the Aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) Reared on Tobacco (Nicotiana tabacum L.) Diferencias en el Metabolismo de Detoxificación entre dos Linajes Clonales del áfido Myzus persicae (Sulzer) (Hemiptera: Aphididae) creados sobre tabaco (Nicotiana tabacum L.)
Marco A Cabrera-Brandt,Eduardo Fuentes-Contreras,Christian C Figueroa
Chilean Journal of Agricultural Research , 2010,
Abstract: Myzus persicae (Sulzer) is a highly polyphagous aphid species, with a subspecies (M. persicae nicotianae) well adapted to tobacco (Nicotiana tabacum L.). We evaluated the effect of this host plant on the aphid performance and detoxification enzymes, in order to test the participation of xenobiotic metabolism on the ability of this aphid to overcome the tobacco chemical defences. Two genotypes, one corresponding to the only M. persicae nicotianae genotype reported in Chile on tobacco, and one genotype belonging to M. persicae sensu stricto were reared on tobacco and pepper (Capsicum annuum L.), respectively. M. persicae nicotianae showed a significantly higher intrinsic rate of increase (r m) on pepper than on tobacco, and M. persicae s.s. performed similarly, but with no reproduction at all on tobacco. In order to evaluate the effect of tobacco on detoxification enzymes, esterases, glutathione S-transferases (GST) and cytochrome P-450 monooxygenases (MO) were determined in both selected aphid genotypes after 12, 24, 36, 48 and 72 h of rearing on tobacco and pepper. M. persicae nicotianae exhibited the higher total esterase activities when reared on tobacco than on pepper after 48 h of rearing, while the activities of GST and MO did not show any significant difference between host-plants and duration of treatment. For M. persicae s.s., no significant differences were observed among host-plants for the studied enzymes. These results suggest a participation of the esterases, on the ability of this M. persicae nicotianae to overcome the tobacco defences. Myzus persicae (Sulzer) es un áfido polífago que incluye a Myzus persicae nicotianae, una subespecie altamente adaptada sobre tabaco (Nicotiana tabacum L.). Evaluamos el efecto del tabaco sobre el desempe o biológico y sobre determinadas enzimas de detoxificación en áfidos, para estudiar su participación en la capacidad de M. persicae nicotianae de superar las defensas químicas del tabaco. Dos genotipos de M. persicae, uno correspondiente al único genotipo perteneciente a M. persicae nicotianae reportado en Chile sobre tabaco y el otro perteneciente a M. persicae sensu stricto, fueron criados sobre tabaco y pimentón (Capsicum annuum L.), respectivamente. M. persicae nicotianae mostró una tasa intrínseca de crecimiento (r m) significativamente mayor sobre pimentón que sobre tabaco, mientras que M. persicae s.s. no se reprodujo sobre tabaco. Para evaluar los efectos del tabaco sobre el metabolismo de detoxificación, se determinó la actividad de las enzimas esterasas, glutation S-transferasas (GST) y citocromo
Localization and defects in axial (In,Ga)N/GaN nanowire heterostructures investigated by spatially-resolved luminescence spectroscopy
Jonas L？hnemann,Christian Hauswald,Martin W？lz,Uwe Jahn,Michael Hanke,Lutz Geelhaar,Oliver Brandt
Physics , 2014, DOI: 10.1088/0022-3727/47/39/394010
Abstract: (In,Ga)N insertions embedded in self-assembled GaN nanowires are of current interest for applications in solid state light emitters. Such structures exhibit a notoriously broad emission band. We use cathodoluminescence spectral imaging in a scanning electron microscope and micro-photoluminescence spectroscopy on single nanowires to learn more about the mechanisms underlying this emission. We observe a shift of the emission energy along the stack of six insertions within single nanowires that may be explained by compositional pulling. Our results also corroborate reports that the localization of carriers at potential fluctuations within the insertions plays a crucial role for the luminescence of these nanowire based emitters. Furthermore, we resolve contributions from both structural and point defects in our measurements.
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