Quantitative analysis of immunolabeling for serotonin and for glutamate transporters after administration of imipramine and citalopram

Serotonin (5-hydroxytryptamine, 5-HT) is an amine neurotransmitter derived from tryptophan and is important in brain systems regulating mood, emotional behavior, and sleep. Selective serotonin reuptake inhibitor (SSRI) drugs are used to treat disorders such as depression, stress, eating disorders, autism, and schizophrenia. It is thought that these drugs act to prolong the action of 5-HT by blocking reuptake. This may lead to decreased 5-HT content in the nerve fibers themselves; however, this has not previously been directly demonstrated. We have studied the effects of administration of two drugs, imipramine and citalopram, on levels of 5-HT in nerve fibers in the murine brain. Quantitative analysis of the areal density of 5-HT fibers throughout the brain was performed using ImageJ software. While a high density of fibers was observed in mid- and hind-brain regions and areas such as thalamus and hypothalamus, densities were far lower in areas such as cortex, where SSRIs might be thought to exert their actions. As anticipated, imipramine and citalopram produced a decline in 5-HT levels in nerve fibers, but the result was not uniform. Areas such as inferior colliculus showed significant reduction whereas little, if any, change was observed in the adjacent superior colliculus. The reason for, and significance of, this regionality is unclear. It has been proposed that serotonin effects in the brain might be linked to changes in glutamatergic transmission. Extracellular glutamate levels are regulated primarily by glial glutamate transporters. Qualitative evaluation of glutamate transporter immunolabeling in cortex of control and drug-treated mice revealed no discernable difference in intensity of glutamate transporter immunoreactivity. These data suggest that changes in intracellular and extracellular levels of serotonin do not cause concomitant changes in astroglial glutamate transporter expression, and thus cannot represent a mechanism for the delayed efficacy of antidepressants when administered clinically. © 2005 Elsevier B.V. All rights reserved.

Age-related differences in rapid muscle activation after rate of force development training of the elbow flexors

In young adults, improvements in the rate of force development as a result of resistance training are accompanied by increases in neural drive in the very initial phase of muscle activation. The purpose of this experiment was to determine if older adults also exhibit similar adaptations in response to rate of force development (RFD) training. Eight young (21-35 years) and eight older (60-79 years) adults were assessed during the production of maximum rapid contractions, before and after four weeks of progressive resistance training for the elbow flexors. Young and older adults exhibited significant increases (P< 0.01) in peak RFD, of 25.6% and 28.6% respectively. For both groups the increase in RFD was accompanied by an increase in the root mean square (RMS) amplitude and in the rate of rise (RER) in the electromyogram (EMG) throughout the initial 100 ms of activation. For older adults, however, this training response was only apparent in the brachialis and brachioradialis muscles. This response was not observed in surface EMG recorded from the biceps brachii muscle during either RFD testing or throughout training, nor was it observed in the pronator teres muscle. The minimal adaptations observed for older adults in the bifunctional muscles biceps brachii and pronator teres are considered to indicate a compromise of the neural adaptations older adults might experience in response to resistance training.

Reduced between-hospital variation in short term survival after acute myocardial infarction: the result of improved cardiac care?

Objectives: To re-examine interhospital variation in 30 day survival after acute myocardial infarction ( AMI) 10 years on to see whether the appointment of new cardiologists and their involvement in emergency care has improved outcome after AMI. Design: Retrospective cohort study. Setting: Acute hospitals in Scotland. Participants: 61 484 patients with a first AMI over two time periods: 1988 - 1991; and 1998 - 2001. Main outcome measures: 30 day survival. Results: Between 1988 and 1991, median 30 day survival was 79.2% ( interhospital range 72.1 - 85.1%). The difference between highest and lowest was 13.0 percentage points ( age and sex adjusted, 12.1 percentage points). Between 1998 and 2001, median survival rose to 81.6% ( and range decreased to 78.0 - 85.6%) with a difference of 7.6 ( adjusted 8.8) percentage points. Admission hospital was an independent predictor of outcome at 30 days during the two time periods ( p< 0.001). Over the period 1988 - 1991, the odds ratio for death ranged, between hospitals, from 0.71 ( 95% confidence interval ( CI) 0.58 to 0.88) to 1.50 ( 95% CI 1.19 to 1.89) and for the period 1998 - 2001 from 0.82 ( 95% CI 0.60 to 1.13) to 1.46 ( 95% CI 1.07 to 1.99). The adjusted risk of death was significantly higher than average in nine of 26 hospitals between 1988 and 1991 but in only two hospitals between 1998 and 2001. Conclusions: The average 30 day case fatality rate after admission with an AMI has fallen substantially over the past 10 years in Scotland. Between-hospital variation is also considerably less notable because of better survival in the previously poorly performing hospitals. This suggests that the greater involvement of cardiologists in the management of AMI has paid dividends.

Controlled trial of hyperbaric oxygen treatment for alkali corneal burn in the rabbit

Purpose: To evaluate the efficacy of hyperbaric oxygen therapy in the treatment of alkali-induced corneal burns in an animal model. Methods: Twenty-four rabbits were randomized into a control group (n = 12) and hyperbaric oxygen treatment group (n = 12). After induction of anaesthesia, the alkali burn model was established by application of 1 N sodium hydroxide to one eye of each rabbit. The hyperbaric oxygen treatment group was treated each day for 21 days with hyperbaric oxygen at 2.4 Atmospheres Absolute (ATA) for 1 h. The eyes of the animals were examined daily for 2 weeks and then weekly until the end of the trial. The principal endpoint was that of perforation of the cornea at which time the animals were killed with a lethal dose of either intravenous or intraperitoneal barbiturate and the eyes immediately enucleated and fixed in 10% neutral buffered formalin. All animals in which complete healing took placed were also killed, the eyes removed, fixed and examined histologically. Photographs were taken of the rabbit's eyes at weekly intervals and the area of vascularization and epithelial defects in the hyperbaric and control groups were compared. Results: Equal numbers (seven) of the control and hyperbaric oxygen treated groups had perforated corneas and there was no statistical difference in the mean time to perforation (control 30.1 days; treated 30 days). There was also no statistical difference between the two groups with respect to epithelial defect size. Conclusion: Treatment with hyperbaric oxygen for 1 h daily for 21 days had no beneficial effect on alkali-induced corneal burns.