Prenatal exposure to MDMA alters noradrenergic neurodevelopment in the rat.

3,4-methylenedioxymethamphetamine (MDMA; ecstasy) binds with high affinity to the norepinephrine transporter (NET), making the noradrenergic system a potential target during fetal exposure. Recent data indicate that adult rats that had been prenatally exposed to MDMA display persistent deficits in working memory and attention; behaviors consistent with abnormal noradrenergic signaling in the forebrain. The present study was designed to investigate whether prenatal exposure to MDMA from embryonic days 14-20 affects the structure and/or function of the noradrenergic system of the rat on postnatal day 21. Offspring that were prenatally exposed to MDMA exhibited an increase in noradrenergic fiber density in the prelimbic region of the prefrontal cortex and the CA1 region of the hippocampus that was not accompanied by an increase in the number of noradrenergic neurons in the locus coeruleus. Direct tissue autoradiography using tritiated nisoxetine demonstrated that while NET binding was not altered in the prelimbic cortex, the dentate gyrus, or the locus coeruleus, it was increased in the CA1, CA2, and CA3 regions of the hippocampus. Basal levels of norepinephrine were increased in the prefrontal cortex and the nucleus accumbens of MDMA-exposed rats, as compared to saline-treated controls. These findings indicate that prenatal exposure to MDMA results in structural changes in the noradrenergic system as well as functional alterations in NE neurotransmission in structures that are critical in attentional processing.

Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4 weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.

Effects of short-term concentric vs. eccentric resistance training on single muscle fiber MHC distribution in humans.

The purpose of this investigation was to determine the effects of a concentric vs. eccentric resistance training program on single muscle fiber myosin heavy chain (MHC) adaptations in humans. Fifteen sedentary, healthy males were divided into three groups: concentric training (CTG) (n = 6, 24.2 +/- 1.7 y, 181 +/- 2 cm, 82.5 +/- 4.6 kg), eccentric training (ETG) (n = 6, 23.7 +/- 1.6 y, 178 +/- 3 cm, 90.4 +/- 6.1 kg), and control (CTL) (n = 3, 23 +/- 1.5 y, 181 +/- 2 cm, 97 +/- 13.2 kg). The subjects performed 4 sets of 8 unilateral repetitions starting at 80 % of concentric 1-RM, 3 days/week for a total of 4 weeks. Subjects were tested pre- and post-training for concentric 1-RM. Muscle biopsies were obtained from the vastus lateralis pre- and post-training for determination of single fiber MHC isoform distribution using SDS-PAGE/silver staining (100 fibers analyzed/subject pre- and post-training). Fibers expressing more than one MHC isoform (i.e., hybrid fibers) were analyzed for relative MHC isoform proportions via densitometry. The training program resulted in a 19 % 1-RM strength gain for CTG (p < 0.05) with no change in ETG or CTL. MHC-IIx fibers decreased by 7 % in CTG (p < 0.05) and ETG had an 11 % increase in total hybrids (MHC-I/IIa + MHC-IIa/IIx) (p < 0.05). No other differences were noted in MHC distribution among the three groups. Densitometry analysis of hybrid fibers showed no change in relative MHC isoform proportions pre- to post-training for any group. These data suggest that the MHC distribution did not change dramatically as a result of 4 weeks of concentric vs. eccentric resistance training despite the increase in whole muscle strength from concentric muscle actions.

Dynamic cardiomyoplasty: clinical follow-up results.

From 1985 to April 1990, 78 clinical dynamic cardiomyoplasty procedures were performed using the latissimus dorsi muscle stimulated with the Medtronic Cardiomyoplasty System. Indications for surgery were mostly ischemic and idiopathic dilated cardiomyopathies with patients in severe cardiac insufficiency (NYHA Class III and IV). Results of this multicenter study (11 centers) indicate that the dynamic cardiomyoplasty procedure can be transferred and reproduced in many centers with low perioperative mortality and that it improves the functional status of patients who survive the procedure. The survival rate suggests a long-term benefit (average implant time: 11.7 months). Although clinical functional improvement was reported, actual hemodynamic augmentations could not be clearly demonstrated under the protocol. Further studies of functional and hemodynamic parameters are necessary to determine if dynamic cardiomyoplasty is efficacious for a well-defined group of congestive heart failure patients. These points will be addressed in forthcoming studies.

Acute and long-term atrial and ventricular stimulation thresholds with a steroid-eluting electrode.

Thirty leads with a steroid-eluting electrode (Medtronic 4003 and 4503) have been implanted in 24 patients, 11 in the atrium and 19 in the ventricle. Six patients received the steroid lead in both atrium and ventricle. The stimulation thresholds were followed using Elema pulse generators with Vario function in 15 patients (11 atrial leads and 10 ventricular leads) during 11 +/- 3 months (mean +/- SD). At 0.5 ms pulse duration the mean atrial and ventricular thresholds were 0.55 Volt +/- 0.22 and 0.39 Volt +/- 0.22 respectively at implant, 0.94 Volt +/- 0.13 and 0.82 Volt +/- 0.16 after 12 months. During the entire follow-up period both atrial and ventricular mean thresholds never exceeded 1 V.

Modern atrial and ventricular leads for permanent cardiac pacing.

Three hundred and fifteen transvenous pacing leads of various modern designs have been assessed over a period of three years. Of these, 103 were implanted in the atrium and 212 in the ventricle. Screw-in leads in the right atrial appendage and short tined leads in the ventricle have resulted in the virtual elimination of lead displacement, and a very low incidence of other lead related problems. In two lead systems it has been found advantageous to have both leads constructed of urethane.