Limitations of fluorocarbons in reducing myocardial infarct size

The effects of the oxygen-carrier fluorocarbons on myocardial infarct size were assessed in non-exchange-transfused dogs subjected either to a 3-hour occlusion of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion (protocol I) or to a 5-hour permanent LAD occlusion (protocol II). Fluorocarbon administration was begun 30 minutes after LAD occlusion and was continued over the entire period of ischemia. After 5 hours, the hearts were excised and areas of necrosis were visualized by triphenyl tetrazolium chloride staining while risk regions were assessed by radiolabeled microspheres injected after coronary occlusion just before the onset of therapy, and further, in protocol I, by thallium-201 perfusion imaging performed at the end of fluorocarbon administration. In protocol I experiments, the ratio of necrotic area to area at risk was 81 +/- 35% (mean +/- standard deviation) in control saline-treated dogs (n = 6) and 67 +/- 27% in fluorocarbon-treated dogs (n = 6) (difference not significant). There was no significant difference between risk regions measured after and before fluorocarbon treatment. In protocol II, the ratio of necrotic area to area at risk was 47 +/- 30% in control dogs (n = 5) and 63 +/- 29% in fluorocarbon-treated dogs (n = 5) (difference not significant). However, in control dogs, the ratio of necrotic area to area at risk increased from 47 +/- 30% in the dogs that underwent permanent occlusion to 81 +/- 35% in the group that underwent reperfusion (p less than 0.001) while this ratio was similar in the corresponding subsets of fluorocarbon-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Computer-Based Simulation of the Bielschowsky Head-Tilt Test Using the SEE++ Software System

Introduction: Latest measurements of the vestibulo-ocular reflex (VOR) allowed the integration of the simulation of the Bielschowsky head-tilt test (BHTT) into the SEE++ software system. SEE++ realizes a biomechanical model of the human eye in order to simulate eye motility disorders and strabismus surgeries. With the addition of the BHTT it can now also be used for differential-diagnostic simulations of complex disorders (e.g., superior oblique palsies). Methods: In order to simulate the BHTT in SEE++, the user can freely choose the desired head-tilt angle from ?45° to +45°. The chosen angle is shown in the 3D view with a human body model and is also used in the calculation of the Hess-Lancaster test. Results: The integration of the BHTT offers an additional improvement of the possibilities for simulating eye motility disorders. Moreover, SEE++ allows the creation of a video of the “virtual patient” while tilting the head from one side to the other, which shows dynamic changes in the simulated Hess-diagrams. Discussion: Comparisons of simulation results with patient-measured data showed a good correlation between the simulated and the measured data. Further comparisons with patient data are planned.     

M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic, blocks dizocilpine-induced prepulse inhibition deficits in Sprague-Dawley and Wistar rats.

In a recent study using Wistar rats, the serotonergic 5-HT2 receptor antagonists ketanserin and risperidone reduced the disruptive effects of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine on prepulse inhibition (PPI), suggesting that there is an interaction between serotonin and glutamate in the modulation of PPI. In contrast, studies using the noncompetitive NMDA antagonist phencyclidine (PCP) in Sprague-Dawley rats found no effect with 5-HT2 antagonists. To test the hypothesis that strain differences might explain the discrepancy in these findings, risperidone was tested for its ability to reduce the PPI-disruptive effects of dizocilpine in Wistar and Sprague-Dawley rats. Furthermore, to determine which serotonergic receptor subtype may mediate this effect, the 5-HT2A receptor antagonist M100907 (formerly MDL 100,907) and the 5-HT2C receptor antagonist SDZ SER 082 were tested against dizocilpine. Recent studies have found that the PPI-disruptive effects of PCP are reduced by the alpha 1 adrenergic receptor antagonist prazosin. Furthermore, the alpha 1 receptor agonist cirazoline disrupts PPI. As risperidone and M100907 have affinity at the alpha 1 receptor, a final study examined whether M100907 would block the effects of cirazoline on PPI. Risperidone partially, but nonsignificantly, reduced the effects of dizocilpine in Wistar rats, although this effect was smaller than previously reported. Consistent with previous studies, risperidone did not alter the effects of dizocilpine in Sprague-Dawley rats. Most importantly, M100907 pretreatment fully blocked the effect of dizocilpine in both strains; whereas SDZ SER 082 had no effect. M100907 had no influence on PPI by itself and did not reduce the effects of cirazoline on PPI. These studies confirm the suggestion that serotonin and glutamate interact in modulating PPI and indicate that the 5-HT2A receptor subtype mediates this interaction. Furthermore, this interaction occurs in at least two rat strains.     

No evidence for an involvement of alleles of polymorphisms in the serotonin1Dbeta and 7 receptor genes in obesity, underweight or anorexia nervosa.

The serotonergic (5-hydroxytryptamine, 5-HT) system has been implicated in body weight regulation and in the etiology of anorexia nervosa (AN). Here we describe the screening of the known Phe-124-Cys polymorphism in the 5-HT1Dbeta receptor gene and of the known Pro-279-Leu polymorphism in the 5-HT7 receptor gene. For association tests allele frequencies were compared between up to 393 extremely obese children and adolescents, 142 underweight students and 84 patients with AN. None of the association tests revealed nominal P-values below 0.3. We conclude that a major role of the investigated polymorphisms in body weight regulation or AN appears unlikely.