Zur Frage der Konstanz und Abgrenzbarkeit myeloarchitektonischer Rindenfelder

Zusammenfassung An Hand von Faserpräparaten der hinteren Zentralwindung von 11 verschiedenen Hemisphären und des Schläfenlappenpols von 10 verschiedenen Hemisphären wurde zu zeigen versucht, daß die an den genannten Rindenstellen beschriebenen Felder konstant bei allen Individuen vorkommen und sich stets scharf abgrenzen lassen. Zur raschen Orientierung an der Hirnrinde sowie zur genauen Bestimmung des Sitzes von Herden erscheint die myeloarchitektonische Methode besonders geeignet.Mit 9 Textabbildungen.Herrn Prof. Kleist in Verehrung und Dankbarkeit zum 75. Geburtstag gewidmet.     

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: relations to timed performance

The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (lambdaL), an index of axonal length or number, and transverse diffusivity (lambdaT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age's effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.     

Predominance of IncL/M and IncF plasmid types among CTX‐M‐ESBL‐producing Escherichia coli and Klebsiella pneumoniae in Bulgarian hospitals

Our objective was to investigate the plasmid replicon‐types involved in spread of ESBLs among Bulgarian Klebsiella pneumoniae and Escherichia coli. Sixty‐three isolates, with transferable beta‐lactam resistance determinants, collected between 2007 and 2009 in six medical institutions, were analysed with respect to their antimicrobial susceptibility, ESBL‐, RAPD‐, and plasmid replicon‐type. Phylogenetic typing and screening for the O25b‐ST131 lineage were carried out for E. coli. The predominant ESBLs were CTX‐M‐15 (81%) among E. coli and CTX‐M‐3 (58%) among K. pneumoniae. Other sporadically found ESBLs were SHV‐12 and TEM‐139, and for the first time in Bulgaria, CTX‐M‐1 and CTX‐M‐14. Replicon typing revealed that plasmids carrying bla_CTX‐M‐3 exclusively belonged to IncL/M‐type, while bla_CTX‐M‐15 was predominantly (94%) associated with IncF‐type plasmids. Among E. coli, 59% of the isolates were clonally related. Isolates of that cluster produced CTX‐M‐15, belonged to the O25b‐ST131 lineage, predominantly harboured plasmids with the FIA replicon, and were found in five centres. Among CTX‐M‐3‐producing K. pneumoniae, two prevailing RAPD‐types were found, one remained restricted to one centre and the second was found in three centres. The incompatibility groups IncN and IncA/C linked with bla_SHV‐12 respectively bla_TEM‐139 were found only once. To the best of our knowledge, this is the first detailed investigation of plasmids carrying ESBL genes among Bulgarian isolates demonstrating wide distribution of conjugative IncF plasmids among CTX‐M‐15‐producing E. coli and IncL/M plasmids among CTX‐M‐3 positive K. pneumoniae isolates.     

Quantification of glutamate and glutamine using constant‐time point‐resolved spectroscopy at 3 T

Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant‐time point‐resolved spectroscopy (CT‐PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time‐domain basis set was constructed taking into account metabolite T₂ relaxation times and dephasing from B₀ inhomogeneity. Metabolite concentrations were estimated by fitting the basis one‐dimensional CT‐PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom‐built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantification revealed increased Gln after 16 weeks and increased Glu after 24 weeks of vaporized ethanol exposure in ethanol‐treated compared with control rats. Without separate quantification, the signal from the combined resonances of Glu and Gln (Glx) showed an increase at both 16 and 24 weeks in ethanol‐exposed rats, precluding the determination of the independent and differential contribution of each metabolite at each time. Copyright © 2012 John Wiley & Sons, Ltd.     

In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1‐13C] and [2‐13C]pyruvate

Hyperpolarized ¹³C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl‐coenzyme A (acetyl‐CoA). [1‐¹³C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in ¹³C‐bicarbonate production after dichloroacetate (DCA) administration. With [1‐¹³C]pyruvate, the ¹³C label is released as ¹³CO₂/¹³C‐bicarbonate, and, hence, does not allow us to follow the fate of acetyl‐CoA. Pyruvate labeled in the C₂ position has been used to track the ¹³C label into the TCA (tricarboxylic acid) cycle and measure [5‐¹³C]glutamate as well as study changes in [1‐¹³C]acetylcarnitine with DCA and dobutamine. This work investigates changes in the metabolic fate of acetyl‐CoA in response to metabolic interventions of DCA‐induced increased PDC flux in the fed and fasted state, and increased cardiac workload with dobutamine in vivo in rat heart at two different pyruvate doses. DCA led to a modest increase in the ¹³C labeling of [5‐¹³C]glutamate, and a considerable increase in [1‐¹³C]acetylcarnitine and [1,3‐¹³C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2‐¹³C]lactate, [2‐¹³C]alanine and [5‐¹³C]glutamate. The change in glutamate with dobutamine was observed using a high pyruvate dose but not with a low dose. The relative changes in the different metabolic products provide information about the relationship between PDC‐mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways. Using a high dose of pyruvate may provide an improved ability to observe changes in glutamate. Copyright © 2013 John Wiley & Sons, Ltd.     

Differential effects of progestins on hemostasis

Recently large, prospective, randomized studies on hormone replacement therapy (HRT) have indicated that the progestin use might interfere with hemostasis and thus increase venous thrombotic events. Therefore, available publications were evaluated to determine whether progestins interfere with hemostasis, either when given alone via oral or parenteral routes or in combination with ethinylestradiol as synthetic estrogen or natural estrogens. There are indications that such interference is dependent upon the type and dose of the progestin, the route of application, the length of treatment and the type and dose of the estrogen with which it is combined. For natural progesterone, no negative effects on the hemostatic system were seen with either oral or parenteral application, in cyclic or continuous regimens, for the doses investigated. Similarly, no unwanted effects were seen with progestin only pills (POP), independent of the type and dose of progestin, or parenteral progestins. With the high-dose progestins used in gynaecological oncology, the increased activation of the hemostatic system resulting from the disease itself has to be taken into account when looking at any increased incidence of thromboembolic events in these patients. For estrogen/progestin combinations, the risk of venous thromboembolism is attributed to the estrogen used. Recent studies showed an increased rate of thromboembolic events in association with desogestrel-and gestodene-containing oral contraceptives, compared with those containing levonorgestrel. With HRT, a decrease in antithrombin factors could explain the increased rate of venous thrombotic events. In conclusion, progestins seems to have different effects on the hemostatic system due to their different pattern of biological activities. This was also shown in the arterial vascular system, where some progestins may reduce the endothelium-dependent vasodilating action of estrogens and stimulate intima proliferation and upregulate thrombin receptor expression while other progestins did not.     

One-way avoidance acquisition and cellular density in the basolateral amygdala: Strain differences in Roman high- and low-avoidance rats

The goal of the present experiment was to study the performance of inbred Roman high- (RHA-I) and low- (RLA-I) avoidance rats in one-way avoidance learning and to relate the behaviour of the animals to cellular density in the basolateral amygdala (BLA), a brain region related to fear and anxiety. Thus, females from both strains were exposed either to 30 s or 1 s in the safe place as a function of experimental condition, until they reached five consecutive avoidance responses. Thereafter, the rats were perfused, and their brains sectioned in 40 μm coronal sections, stained with cresyl violet. The area (percentage of field) corresponding to the BLA structures was quantified by computerized-assisted image analysis. The results indicated that RLA-I showed a significantly poorer acquisition of the one-way avoidance task than did RHA-I rats, but only when safe time was the shortest (1 s). In addition, the number of trials needed to reach the behavioural acquisition criterion was negatively correlated with BLA cellular density in RLA-I rats. These data suggest the possibility of relating behavioural and neuro-anatomical indexes, enabling exploration of the biological basis of fear/anxiety behaviours.