BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity.     

Subtraction of Compton-scattered photons in single-photon emission computerized tomography

A technique for scatter correction in single photon emission computerized tomography (SPECT) is described. The method is based on "deconvolution" of scattered events from the measured profile data. The function defining the scatter distribution was determined from measurements with a line source in circular and rectangular water phantoms. The accuracy of the method was tested on a simple phantom simulating a SPECT investigation of the liver. The indicated ratio of the activity concentration in a photon-deficient area, 60 mm diameter in the "liver", relative to its surroundings, was 0.28/1 without scatter correction and 0.01/1 with the correction.     

Three-dimensional reconstruction from cone-beam data in O(N3 log N) time

We have used direct Fourier techniques to modify and implement the 3D reconstruction method from cone-beam projections proposed by Grangeat. In this way we manage to decrease the computational complexity from O(N4) to O(N3 log N). Just as Grangeat's original method is exact in the mathematical sense, so is our method, provided a complete set of projection data is acquired. Also in accordance with Grangeat, our algorithm consists of two distinct phases: phase 1, from cone-beam data to derivatives of Radon data; phase 2, from derivatives of Radon data to reconstructed 3D object. In phase 1 we use the direct Fourier method in reverse to obtain line integrals in the detector plane. In phase 2 the 2D linogram method is employed for reconstruction of vertical and horizontal planes in the Radon space.     

Serum concentration and protein binding of thioridazine and its metabolites in patients with chronic alcoholism

Summary The blood chemistry and clinical pharmacokinetics of thioridazine and its metabolites, side-chain sulphoxide, side-chain sulphone and ring sulphoxide, were studied in 31 alcoholics and were compared with values in 17 thioridazine-treated controls without alcoholism. Pathological blood chemistry values, including abnormal liver function and protein concentrations, were common among the alcoholics. In relation to dosage, the majority had a low serum concentration of thioridazine and at a given concentration of thioridazine they had high serum concentrations of its metabolites. Positive intercorrelations were found between pathological liver function tests, prolonged serum half-life and increased serum concentration of thioridazine. The free fractions of thioridazine, side-chain sulphoxide and ring sulphoxide were significantly higher and those of the side-chain sulphone lower in the alcoholics than in the controls. The free fractions of side-chain and ring sulphoxide were significantly increased in patients with a low concentration of ₁-acid glycoprotein.     

Clinical Significance of Specific Gravity of Spinal Anaesthetic Agents Two Double-Blind Studies with Hyperbaric 5% Lidocaine

In two double-blind studies two hyperbaric 5% lidocaine solutions containing glucose in concentrations of 75 mg/ml and 50 mg/ml, respectively, were compared. The onset and total onset time, spread, intensity, duration of analgesia and motor block were studied. The spinal anaesthesia was given with the patient either sitting or in the lateral recumbent position. A tendency to a longer duration of anaesthesia near dermatomes Th X-L II and L IV-L V was noted in the group of patients in the sitting position and receiving lidocaine with a lower glucose concentration. Otherwise there were no differences between the two lidocaine solutions. The result shows that the glucose concentration can be reduced from 75 to 50 mg/ml in "heavy" lidocaine without any clinical disadvantage. This means a more isotonic solution in relation to the cerebrospinal fluid, resulting in milder osmotic effects on interspinal structures.     

Is there increased intervertebral mobility in isthmic adult spondylolisthesis? A matched comparative study using roentgen stereophotogrammetry

STUDY DESIGN: By roentgen stereophotogrammetric technique, the intervertebral mobility of the spondylolytic segment in eight patients was measured and compared with the mobility of eight nonspondylolytic patients matched according to sex, afflicted segment, and grade of disc degeneration. OBJECTIVES: To compare the intervertebral mobility of a spondylolytic segment with the mobility of a segment without spondylolysis in adult patients with back pain. SUMMARY OF BACKGROUND DATA: Evidenced by the resulting olisthetic deformity and supported by the outcome from prior investigations, spondylolysis is assumed to induce spinal segmental instability/hypermobility. METHODS: After percutaneous application of tantalum indicators for roentgen stereophotogrammetric technique, the intervertebral translations of the spondylolytic fifth lumbar vertebra were measured in eight adult patients with low back pain and low-grade olisthesis. Eight other patients without spondylolysis but with low back pain presumably on degenerative basis were chosen for comparison and had an identical measuring procedure using roentgen stereophotogrammetric technique. The two groups were matched in pairs according to sex, afflicted segment, and grade of disc degeneration. RESULTS: No significant difference was registered considering the intervertebral mobility for matched pairs in the two groups neither along the sagittal nor the vertical axis. The transverse translations were mostly negligible in both groups. CONCLUSION: The spondylolytic defect in pars interarticularis does not cause permanent instability/hypermobility detectable in the adult patient with low back pain and low-grade olisthesis.     

Tranexamic acid reduces blood loss in total hip replacement surgery

Intraoperatively administered, tranexamic acid (TA) does not reduce bleeding in total hip replacement (THR). Therefore, its prophylactic use was attempted in the present study because this has been shown to be more effective in cardiac surgery. We investigated 40 patients undergoing THR in a prospective, randomized, double-blinded study. Twenty patients received TA given in two bolus doses of 10 mg/kg each, the first just before surgical incision and the second 3 h later. In addition, a continuous infusion of TA, 1.0 mg. kg(-1). h(-1) for 10 h, was given after the first bolus dose. The remaining 20 patients formed a control group. Both groups used preoperative autologous blood donation and intraoperative autotransfusion. Intraoperative bleeding was significantly less (P: = 0.001) in the TA group compared with the control group (630 +/- 220 mL vs 850 +/- 260 mL). Postoperative drainage bleeding was correspondingly less (P: = 0.001) (520 +/- 280 vs 920 +/- 410 mL). Up to 10 h postoperatively, plasma D-dimer concentration was halved in the TA group compared with the control group. One patient in each group had an ultrasound-verified late deep vein thrombosis. In conclusion, we found TA, administrated before surgical incision, to be efficient in reducing bleeding during THR. Implications: In a prospective, double-blinded study of 40 patients undergoing total hip replacement, the preoperative administration of tranexamic acid reduced bleeding by 35%, probably by decreasing induced fibrinolysis. Whether tranexamic acid therapy can replace predonation of autologous blood or intraoperative autotransfusion requires further study.