Terahertz Néel spin-orbit torques drive nonlinear magnon dynamics in antiferromagnetic Mn2Au.

Antiferromagnets have large potential for ultrafast coherent switching of magnetic order with minimum heat dissipation. In materials such as Mn2Au and CuMnAs, electric rather than magnetic fields may control antiferromagnetic order by Néel spin-orbit torques (NSOTs). However, these torques have not yet been observed on ultrafast time scales. Here, we excite Mn2Au thin films with phase-locked single-cycle terahertz electromagnetic pulses and monitor the spin response with femtosecond magneto-optic probes. We observe signals whose symmetry, dynamics, terahertz-field scaling and dependence on sample structure are fully consistent with a uniform in-plane antiferromagnetic magnon driven by field-like terahertz NSOTs with a torkance of (150 ± 50) cm2 A-1 s-1. At incident terahertz electric fields above 500 kV cm-1, we find pronounced nonlinear dynamics with massive Néel-vector deflections by as much as 30°. Our data are in excellent agreement with a micromagnetic model. It indicates that fully coherent Néel-vector switching by 90° within 1 ps is within close reach.

Emission of coherent THz magnons in an antiferromagnetic insulator triggered by ultrafast spin-phonon interactions.

Antiferromagnetic materials have been proposed as new types of narrowband THz spintronic devices owing to their ultrafast spin dynamics. Manipulating coherently their spin dynamics, however, remains a key challenge that is envisioned to be accomplished by spin-orbit torques or direct optical excitations. Here, we demonstrate the combined generation of broadband THz (incoherent) magnons and narrowband (coherent) magnons at 1 THz in low damping thin films of NiO/Pt. We evidence, experimentally and through modeling, two excitation processes of spin dynamics in NiO: an off-resonant instantaneous optical spin torque in (111) oriented films and a strain-wave-induced THz torque induced by ultrafast Pt excitation in (001) oriented films. Both phenomena lead to the emission of a THz signal through the inverse spin Hall effect in the adjacent heavy metal layer. We unravel the characteristic timescales of the two excitation processes found to be < 50 fs and > 300 fs, respectively, and thus open new routes towards the development of fast opto-spintronic devices based on antiferromagnetic materials.

Central European 2018 hot drought shifts scots pine forest to its tipping point.

The occurrence of hot drought, i.e. low water availability and simultaneous high air temperature, represents a severe threat to ecosystems. Here, we investigated how the 2018 hot drought in Central Europe caused a tipping point in tree and ecosystem functioning in a Scots pine (Pinus sylvestris L.) forest in southwest Germany. Measurements of stress indicators, such as needle water potential, carbon assimilation and volatile organic compound (VOC) emissions, of dominant P. sylvestris trees were deployed to evaluate tree functioning during hot drought. Ecosystem impact and recovery were assessed as ecosystem carbon exchange, normalized difference vegetation index (NDVI) from satellite data and tree mortality data. During summer 2018, needle water potentials of trees dropped to minimum values of -7.5 ± 0.2 MPa, which implied severe hydraulic impairment of P. sylvestris. Likewise, carbon assimilation and VOC emissions strongly declined after mid-July. Decreasing NDVI values from August 2018 onwards were detected, along with severe defoliation in P. sylvestris, impairing ecosystem carbon flux recovery in 2019, shifting the forest into a year-round carbon source. A total of 47% of all monitored trees (n = 368) died by September 2020. NDVI recovered to pre-2018 levels in 2019, likely caused by emerging broadleaved understorey species. The 2018 hot drought had severe negative impacts on P. sylvestris. The co-occurrence of unfavourable site-specific conditions with recurrent severe droughts resulted in accelerated mortality. Thus, the 2018 hot drought pushed the P. sylvestris stand towards its tipping point, with a subsequent vegetation shift to a broadleaf-dominated forest.

The 2018 hot drought pushed conifer wood formation to the limit of its plasticity: Consequences for woody biomass production and tree ring structure.

Hot droughts are expected to increase in Europe and disturb forest ecosystem functioning. Wood formation of trees has the potential to adapt to those events by compensatory mechanisms between the rates and durations of tracheid differentiation to form the typical pattern of vital wood anatomical structures. We monitored xylogenesis and measured wood anatomy of mature silver fir (Abies alba Mill.) and Scots pine (Pinus sylvestris L.) trees along an elevational gradient in the Black Forest during the hot drought year of 2018. We assessed the kinetics of tracheid differentiation and the final tracheid dimensions and quantified the relationship between rates and durations of cell differentiation over the growing season. Cell differentiation kinetics were decoupled, and temperature and water availability signals were imprinted in the tree ring structure. The sudden decline in woody biomass production provided evidence for a disruption in carbon sequestration processes due to heat and drought stress. Growth processes of Scots pine (pioneer species) were mainly affected by the spring drought, whereas silver fir (climax species) growth processes were more disturbed by the summer drought. Our study provides novel insights on the plasticity of wood formation and carbon allocation in temperate conifer tree species in response to extreme climatic events.

Regulation of fatty acid biosynthesis by the global regulator CcpA and the local regulator FabT in Streptococcus mutans.

SMU.1745c, encoding a putative transcriptional regulator of the MarR family, maps to a location proximal to the fab gene cluster in Streptococcus mutans. Deletion of the SMU.1745c (fabTS m ) coding region resulted in a membrane fatty acid composition comprised of longer-chained, unsaturated fatty acids (UFA), compared with the parent strain. Previous reports have indicated a role for FabT in regulation of genes in the fab gene cluster in other organisms, through binding to a palindromic DNA sequence. Consensus FabT motif sequences were identified in S. mutans in the intergenic regions preceding fabM, fabTSm and fabK in the fab gene cluster. Chloramphenicol acetyltransferase (cat) reporter fusions, using the fabM promoter, revealed elevated transcription in a ∆fabTS m background. Transcription of fabTS m was dramatically elevated in cells grown at pH values of 5 and 7 in the ∆ fabTS m background. Transcription of fabTS m was also elevated in a strain carrying a deletion for the carbon catabolite repressor CcpA. Purified FabTS m and CcpA bound to the promoter regions of fabTS m and fabM. Hence, the data indicate that FabTS m acts as a repressor of fabM and fabTS m itself and the global regulator CcpA acts as a repressor for fabTS m .

Use of floss/interdental brushes is associated with lower risk for new cardiovascular events among patients with coronary heart disease.

BACKGROUND AND OBJECTIVE: Periodontitis has been found to be associated with coronary heart disease (CHD) and stroke. However, only little is known about whether periodontitis and associated confounders are associated with new cardiovascular events among patients with CHD. MATERIAL AND METHODS: A total of 942 inpatients with CHD were examined regarding periodontitis, oral care habits, bacteria in the subgingival biofilm and the expression of interleukin-(IL)-6 c. (coding DNA)-174 genotypes (rs 1800793) to determine whether these confounders are associated with new cardiovascular events within a 1-year follow-up period. Adjusted hazard ratios (HR) with respect of age, gender, smoking, body mass index, use of aids for interdental hygiene, plaque index, occurrence of severe periodontitis and further internal diseases such as diabetes, hypertension, dyslipoproteinemia, number of missing teeth, serological parameters and IL-6 genotypes were generated with Cox regression. RESULTS: In all, 941 cardiovascular patients completed the 1-year follow up and 7.3% of the patients achieved the primary endpoint (myocardial infarction: 2.1%, stroke/transient ischemic attack: 1.8%, cardiovascular deaths: 3.4%). Patients who reported practicing interdental cleaning were younger, less likely to be male or to have severe periodontitis, had a reduced tobacco exposure, had fewer missing teeth, less indices for plaque and bleeding on probing and a significant decreased adjusted risk for new cardiovascular events (HR = 0.2, CI 0.06-0.6, p = 0.01) than those patients with CHD who did not report practicing interdental cleaning. We did not obtain significant increased HR for patients with severe periodontitis (HR = 1.2, CI 0.7-2.1, p = 0.53), carriers of the IL-6 genotypes GC or CC (HR = 1.4, CI 0.8-2.5, p = 0.24) and did not find a significant association between the number of detected various oral species and the incidence of the combined endpoint (HR = 0.9, CI 0.8-1.01, p = 0.07). CONCLUSIONS: These findings suggest that flossing and brushing of interdental spaces might reduce the risk for new cardiovascular events among patients with CHD. The hypothesis that interdental cleaning per se reduces the risk of new cardiovascular events should be examined in an interventional study.

Colloid volume loading does not mitigate decreases in central blood volume during simulated haemorrhage while heat stressed.

Heat stress results in profound reductions in the capacity to withstand a simulated haemorrhagic challenge; however, this capacity is normalized if the individual is volume loaded prior to the challenge. The present study tested the hypothesis that volume loading during passive heat stress attenuates the reduction in regional blood volumes during a simulated haemorrhagic challenge imposed via lower-body negative pressure (LBNP). Seven subjects underwent 30 mmHg LBNP while normothermic, during passive heat stress (increased internal temperature ∼1◦C), and while continuing to be heated after intravenous colloid volume loading (11 ml kg⁻¹). Relative changes in torso and regional blood volumes were determined by gamma camera imaging with technetium-99m labelled erythrocytes. Heat stress reduced blood volume in all regions (ranging from 7 to 16%), while subsequent volume loading returned those values to normothermic levels. While normothermic,LBNP reduced blood volume in all regions (torso: 22 ± 8%; heart: 18 ± 6%; spleen: 15 ± 8%). During LBNP while heat stressed, the reductions in blood volume in each region were markedly greater when compared to LBNP while normothermic (torso: 73 ± 2%; heart: 72 ± 3%; spleen: 72 ± 5%, all P<0.001 relative to normothermia). Volume loading during heat stress did not alter the extent of the reduction in these blood volumes to LBNP relative to heat stress alone (torso: 73 ± 1%; heart: 72 ± 2%; spleen: 74 ± 3%, all P>0.05 relative to heat stress alone). These data suggest that blood volume loading during passive heat stress (via 11 ml kg⁻¹ of a colloid solution) normalizes regional blood volumes in the torso, but does not mitigate the reduction in central blood volume during a simulated haemorrhagic challenge combined with heat stress.

Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise.

Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose+1/2 lactate) and metabolic acidosis appears to promote cerebral lactate uptake. However, the influence of pH on cerebral lactate uptake and, in turn, on the cerebral metabolic ratio during exercise is not known. Sodium bicarbonate (Bicarb, 1 M; 350-500 ml) or an equal volume of normal saline (Sal) was infused intravenously at a constant rate during a '2000 m' maximal ergometer row in six male oarsmen (23±2 years; mean±S.D.). During the Sal trial, pH decreased from 7.41±0.01 at rest to 7.02±0.02 but only to 7.36±0.02 (P <0.05) during the Bicarb trial. Arterial lactate increased to 21.4±0.8 and 32.7±2.3 mM during the Sal and Bicarb trials, respectively (P <0.05). Also, the arterial-jugular venous lactate difference increased from-0.03±0.01 mM at rest to 3.2±0.9 mM (P <0.05) and 3.4±1.4 mM (P <0.05) following the Sal and Bicarb trials, respectively. Accordingly, the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials: from 5.8±0.6 at rest to 1.7±0.1 and 1.8±0.2, respectively. The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis during maximal exercise but that did not affect the cerebral lactate uptake and, therefore, the decrease in the cerebral metabolic ratio.

Effect of volume loading on the Frank-Starling relation during reductions in central blood volume in heat-stressed humans.

During reductions in central blood volume while heat stressed, a greater decrease in stroke volume (SV) for a similar decrease in ventricular filling pressure, compared to normothermia, suggests that the heart is operating on a steeper portion of a Frank-Starling curve. If so, volume loading of heat-stressed individuals would shift the operating point to a flatter portion of the heat stress Frank-Starling curve thereby attenuating the reduction in SV during subsequent decreases in central blood volume. To investigate this hypothesis, right heart catheterization was performed in eight males from whom pulmonary capillary wedge pressure (PCWP), central venous pressure and SV (via thermodilution) were obtained while central blood volume was reduced via lower-body negative pressure (LBNP) during normothermia, whole-body heating (increase in blood temperature 1 degrees C), and during whole-body heating after intravascular volume expansion. Volume expansion was accomplished by administration of a combination of a synthetic colloid (HES 130/0.4, Voluven) and saline. Before LBNP, SV was not affected by heating (122 +/- 30 ml; mean +/- s.d.) compared to normothermia (110 +/- 20 ml; P = 0.06). However, subsequent volume loading increased SV to 143 +/- 29 ml (P = 0.003). LBNP provoked a larger decrease in SV relative to the decrease in PCWP during heating (8.6 +/- 1.9 ml mmHg(1)) compared to normothermia (4.5 +/- 3.0 ml mmHg(1), P = 0.02). After volume loading while heat stressed, the reduction in the SV to PCWP ratio during LBNP was comparable to that observed during normothermia (4.8 +/- 2.3 ml mmHg(1); P = 0.78). These data support the hypothesis that a Frank-Starling mechanism contributes to compromised blood pressure control during simulated haemorrhage in heat-stressed individuals, and extend those findings by showing that volume infusion corrects this deficit by shifting the operating point to a flatter portion of the heat stress Frank-Starling curve.

Changes in presumed motor cortical activity during fatiguing muscle contraction in humans.

AIM: Changes in sensory information from active muscles accompany fatiguing exercise and the force-generating capacity deteriorates. The central motor commands therefore must adjust depending on the task performed. Muscle potentials evoked by transcranial magnetic stimulation (TMS) change during the course of fatiguing muscle activity, which demonstrates activity changes in cortical or spinal networks during fatiguing exercise. Here, we investigate cortical mechanisms that are actively involved in driving the contracting muscles. METHODS: During a sustained submaximal contraction (30% of maximal voluntary contraction) of the elbow flexor muscles we applied TMS over the motor cortex. At an intensity below motor threshold, TMS reduced the ongoing muscle activity in biceps brachii. This reduction appears as a suppression at short latency of the stimulus-triggered average of rectified electromyographic (EMG) activity. The magnitude of the suppression was evaluated relative to the mean EMG activity during the 50 ms prior to the cortical stimulus. RESULTS: During the first 2 min of the fatiguing muscle contraction the suppression was 10 +/- 0.9% of the ongoing EMG activity. At 2 min prior to task failure the suppression had reached 16 +/- 2.1%. In control experiments without fatigue we did not find a similar increase in suppression with increasing levels of ongoing EMG activity. CONCLUSION: Using a form of TMS which reduces cortical output to motor neurones (and disfacilitates them), this study suggests that neuromuscular fatigue increases this disfacilitatory effect. This finding is consistent with an increase in the excitability of inhibitory circuits controlling corticospinal output.

Cerebral oxygenation and metabolism during exercise following three months of endurance training in healthy overweight males.

Endurance training improves muscular and cardiovascular fitness, but the effect on cerebral oxygenation and metabolism remains unknown. We hypothesized that 3 mo of endurance training would reduce cerebral carbohydrate uptake with maintained cerebral oxygenation during submaximal exercise. Healthy overweight males were included in a randomized, controlled study (training: n = 10; control: n = 7). Arterial and internal jugular venous catheterization was used to determine concentration differences for oxygen, glucose, and lactate across the brain and the oxygen-carbohydrate index [molar uptake of oxygen/(glucose + (1/2) lactate); OCI], changes in mitochondrial oxygen tension (DeltaP(Mito)O(2)) and the cerebral metabolic rate of oxygen (CMRO(2)) were calculated. For all subjects, resting OCI was higher at the 3-mo follow-up (6.3 +/- 1.3 compared with 4.7 +/- 0.9 at baseline, mean +/- SD; P < 0.05) and coincided with a lower plasma epinephrine concentration (P < 0.05). Cerebral adaptations to endurance training manifested when exercising at 70% of maximal oxygen uptake (approximately 211 W). Before training, both OCI (3.9 +/- 0.9) and DeltaP(Mito)O(2) (-22 mmHg) decreased (P < 0.05), whereas CMRO(2) increased by 79 +/- 53 micromol x 100 x g(-1) min(-1) (P < 0.05). At the 3-mo follow-up, OCI (4.9 +/- 1.0) and DeltaP(Mito)O(2) (-7 +/- 13 mmHg) did not decrease significantly from rest and when compared with values before training (P < 0.05), CMRO(2) did not increase. This study demonstrates that endurance training attenuates the cerebral metabolic response to submaximal exercise, as reflected in a lower carbohydrate uptake and maintained cerebral oxygenation.

Is cerebral oxygenation negatively affected by infusion of norepinephrine in healthy subjects?

BACKGROUND: Vasopressor agents are commonly used to increase mean arterial pressure (MAP) in order to secure a pressure gradient to perfuse vital organs. The influence of norepinephrine on cerebral oxygenation is not clear. The aim of this study was to evaluate the impact of the infusion of norepinephrine on cerebral oxygenation in healthy subjects. METHODS: Three doses of norepinephrine (0.05, 0.1, and 0.15 microg kg(-1) min(-1) for 20 min each) were infused in nine healthy subjects [six males; 26 (6) yr, mean (SD)]. MAP, cerebral oxygenation characterized by frontal lobe oxygenation (Sc(O2)) and internal jugular venous oxygen saturation (Sjv(O2)), middle cerebral artery mean flow velocity (MCA Vmean), cardiac output (CO), and arterial partial pressure for carbon dioxide (Pa(CO2)) were evaluated. RESULTS: MAP increased from 88 (79-101) [median (range)] to 115 (98-128) mm Hg with increasing doses of norepinephrine (P < 0.05), reflecting an increase in total peripheral resistance [20.3 (12.2-25.8) to 25.2 (16.4-28.5) mm Hg min litre(-1); P < 0.05] since CO remained at baseline values. Sc(O2) and Sjv(O2) decreased with increasing doses of norepinephrine, reaching statistical significance with norepinephrine infused at 0.1 microg kg(-1) min(-1) [Sc(O2): 78 (75-94) to 69 (61-83)%; P < 0.05; Sjv(O2): 67 (8) to 64 (7)%; P < 0.01]. MCA Vmean was reduced with each dose of norepinephrine [56.9 (11.2) to 55.0 (11.7) cm s(-1); P < 0.05] and Pa(CO2) lowered from 5.4 (0.4) to 5.1 (0.4) kPa (P < 0.001). CONCLUSIONS: This study suggests that infusion of norepinephrine at 0.1 microg kg(-1) min(-1) or higher may negatively affect cerebral oxygenation.

Cerebral oxygenation decreases during exercise in humans with beta-adrenergic blockade.

AIM: Beta-blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. METHODS: Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non-selective beta-blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near-infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. RESULTS: Arterial lactate and cardiac output increased to 15.3 +/- 4.2 mM and 20.8 +/- 1.5 L min(-1) respectively (mean +/- SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 +/- 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 +/- 6 vs. 69 +/- 8 beats min(-1)) and at exercise exhaustion, cardiac output (16.6 +/- 3.6 L min(-1)) and arterial lactate (9.4 +/- 3.7 mM) were attenuated with a reduction in exercise capacity from 239 +/- 42 to 209 +/- 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 +/- 10 mmHg; P < 0.05). CONCLUSION: Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity.

Symptomatic stenosis of the vertebrobasilar arteries: results of extra- and intracranial stent-PTA.

BACKGROUND AND PURPOSE: About half of all transient ischaemic attacks (TIAs) or strokes in the posterior circulation are caused by the arterial stenosis. The purposes of this study were to determine the safety of stent-assisted percutaneous transluminal angioplasty (stent-PTA) and its efficacy for the prevention of recurrent stroke in patients with symptomatic artery stenosis in the extra- and intracranial posterior circulation. METHODS: Forty-six patients with a previous stroke or TIA who received balloon-mounted coronary stents for vertebral artery origin stenosis (VAOS; 29 patients) or self-expanding nitinol stents for vertebrobasilar intracranial stenosis (VBIS; 17 patients) were followed-up for a mean of 24.1 (VAOS) and 12.7 (VBIS) months. RESULTS: When all cause morbidity/mortality within 30 days from stent-PTA and stroke or death from stroke in the treated vascular territory during the first 12 months of follow-up are combined, the incidence of periprocedural complications and disease progression for the first year is 10.3% in VAOS patients and 17.6% in the VBIS group. Vessel restenosis >/=50% was found in 52.0% of VAOS and in 32.1% of VBIS patients who completed 6 months follow-up. CONCLUSIONS: We observed a higher periprocedural complication rate for patients with VBIS and a higher rate of restenosis in VAOS patients after stent-PTA for symptomatic artery stenosis.

[Diagnosis and therapy of neurological manifestations of inflammatory rheumatic diseases]. / Diagnose und Therapie neurologischer Manifestationen bei entzündlich-rheumatischen Erkrankungen.

Patients with inflammatory rheumatic diseases frequently report symptoms that may indicate an involvement of central and peripheral nervous system in addition to the known musculoskeletal symptoms. The possible symptoms can be as varied as the disease mechanism which causes them. Early correct diagnosis, adequate therapy and regular monitoring of these patients are necessary to prevent permanent disability. This article summarizes current literature on the diagnosis and therapy of neurological manifestations of inflammatory rheumatic diseases including systemic Lupus erythematodes, Behçet's disease, Sjögren's syndrome, systemic vasculitides and sarcoidosis.

Non-invasive characterization of beta-amyloid(1-40) vasoactivity by functional magnetic resonance imaging in mice.

Neurovascular regulation, which is critical to the efficient functioning of the brain, is impaired in Alzheimer's disease and in transgenic mice overexpressing Abeta. Although senile plaques and neurofibrillary tangles represent neuropathological hallmarks of Alzheimer's disease, deposition of Abeta in cerebral blood vessels also likely plays a significant role in this debilitating and fatal disease. Further, soluble Abeta, which shows greater correlation with disease progression and severity than deposited plaques or tangles, displays strong vasoactive properties. The aim of this study was to develop a non-invasive model of cerebral vasoactivity that would ultimately be translatable to Alzheimer's disease as a marker for disease-modifying efficacy of novel small molecule and biologics drugs. Relative changes in cerebral blood volume following relevant doses of soluble Abeta(1-40) (0.01 or 0.1 mg/mouse), PBS, or the reverse peptide, Abeta(40-1) (0.01 or 0.1 mg/mouse), were monitored non-invasively by contrast-enhanced functional magnetic resonance imaging in anesthetized C57BL/6 mice. Experiments were performed on a 7T horizontal bore scanner using gradient echo echo-planar imaging. As expected, PBS and Abeta(40-1) did not induce any significant change in vascular response. In contrast, Abeta(1-40) significantly decreased CBV in a quantifiable, dose-related and region-specific manner. These data demonstrate for the first time the feasibility of characterizing pathogenic Abeta(1-40)-induced vascular dysfunction in vivo using a non-invasive approach. Further, this technique can be readily applied to preclinical screening in a longitudinal manner for novel drugs or antibodies targeting disease modification.

Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI.

BACKGROUND AND PURPOSE: Activation of cannabinoid CB1 and/or CB2 receptors mediates analgesic effects across a broad spectrum of preclinical pain models. Selective activation of CB2 receptors may produce analgesia without the undesirable psychotropic side effects associated with modulation of CB1 receptors. To address selectivity in vivo, we describe non-invasive, non-ionizing, functional data that distinguish CB1 from CB2 receptor neural activity using pharmacological MRI (phMRI) in awake rats. EXPERIMENTAL APPROACH: Using a high field (7 T) MRI scanner, we examined and quantified the effects of non-selective CB1/CB2 (A-834735) and selective CB2 (AM1241) agonists on neural activity in awake rats. Pharmacological specificity was determined using selective CB1 (rimonabant) or CB2 (AM630) antagonists. Behavioural studies, plasma and brain exposures were used as benchmarks for activity in vivo. KEY RESULTS: The non-selective CB1/CB2 agonist produced a dose-related, region-specific activation of brain structures that agrees well with published autoradiographic CB1 receptor density binding maps. Pretreatment with a CB1 antagonist but not with a CB2 antagonist, abolished these activation patterns, suggesting an effect mediated by CB1 receptors alone. In contrast, no significant changes in brain activity were found with relevant doses of the CB2 selective agonist. CONCLUSION AND IMPLICATIONS: These results provide the first clear evidence for quantifying in vivo functional selectivity between CB1 and CB2 receptors using phMRI. Further, as the presence of CB2 receptors in the brain remains controversial, our data suggest that if CB2 receptors are expressed, they are not functional under normal physiological conditions.

Occurrence of Atractolytocestus huronensis (Cestoda, Caryophyllaeidae) in German pond-farmed common carp Cyprinus carpio.

Up to now, the caryophyllid cestode Atractolytocestus huronensis Anthony, 1958, a parasite of common carp, has attracted little attention in Germany. Based on recent publications from the Czech Republic and Hungary, it appears probable that this cestode may be increasingly common in Germany. There is a strong connection between the occurrence of A. huronensis and imports of common carp from the Czech Republic and southern Germany. Although in most cases no clinical alterations in parasitized carp have been observed, care should be taken to avoid further dissemination and to prevent possible losses in commercial pond farming.

Lack of association of lobar intracerebral hemorrhage with apolipoprotein E genotype in an unselected population.

BACKGROUND: Both the upsilon2 and upsilon4 alleles of the apolipoprotein E gene (APOE) have been reported to be overrepresented in lobar intracerebral hemorrhage and to be associated with cerebral amyloid angiopathy (CAA). These studies were performed primarily on the North American population and investigated in partly selected patient cohorts. METHODS: 193 consecutive patients suffering from primary intracerebral hemorrhage (ICH) were included in our study. The localization of the ICH, i.e. cortico-subcortical, deep white matter, basal ganglia, brainstem and cerebellum, was put in relation to the APOE genotype and vascular risk factors. In 101 of these patients, the APOE genotype was also correlated to the presence and distribution of microbleeds and other microangiopathy-related damage, as shown by magnetic resonance imaging (MRI). RESULTS: We found neither an association of a specific APOE genotype with ICH localization nor with microangiopathy-related MRI findings. CONCLUSIONS: In our study of an unselected Central European population, the APOE genotype was not confirmed as a candidate for providing additional diagnostic and potentially prognostic information in patients with ICH.