Electroconvulsive seizures modulate levels of thyrotropin releasing hormone and related peptides in rat hypothalamus, cingulate and lateral cerebellum

We have studied the neuroanatomic extent of electroconvulsive (ECS)-responsive prepro-TRH and TRH-related gene expression and its possible interaction with forced swimming. Young adult male Wistar rats were treated in a 2x2 Latin square protocol of swimming, no swimming, three daily ECS or sham ECS. Sixteen different brain regions were dissected and immunoreactivity measured for TRH (pGlu-His-Pro-NH(2)); TRH-Gly, a TRH precursor; Ps4, a prepro-TRH-derived TRH-enhancing decapeptide, and EEP (pGlu-Glu-Pro-NH(2)). ECS, in addition to elevating TRH-immunoreactivity (TRH-IR), TRH-Gly-IR, Ps4-IR and EEP-IR levels in the limbic regions, as we have previously reported, also significantly increased Ps4-IR levels in hypothalamus, posterior cingulate and lateral cerebellum, and increased TRH-Gly-IR levels in hypothalamus. Interestingly, the combination of ECS and swimming significantly reduced the levels of TRH-Gly-IR in the anterior cingulate compared to the sham ECS-no swim group. The combined use of high-pressure liquid chromatography and the EEP radioimmunoassay (RIA) revealed that pGlu-Tyr-Pro-NH(2) and/or pGlu-Phe-Pro-NH(2) occur in amygdala, anterior cingulate, frontal cortex, entorhinal cortex, lateral cerebellum and striatum and make a substantial contribution to the EEP-IR and TRH-IR. We conclude that ECS can alter the expression and secretion of TRH-related peptides in the hypothalamus, cingulate and lateral cerebellum. Such effects have not previously been reported in these limbic and extra-limbic regions which are increasingly implicated in the autonomic, behavioral and volitional changes which accompany severe depression and its treatment.     

Role of TRH receptors as possible mediators of analeptic actions of TRH-like peptides

A large family of TRH-like peptides in the limbic region of rat brain including pGlu-Glu-Pro-NH(2) (EEP), pGlu-Val-Pro-NH(2) (Val(2)-TRH), Leu(2)-TRH, Phe(2)-TRH and Tyr(2)-TRH has recently been discovered. TRH (pGlu-His-Pro-NH(2)) has antidepressant, neuroprotective, analeptic, anticonvulsant, antiamnesic and euphoric properties, and other TRH-like peptides such as EEP exert several of these effects. A new TRH receptor (TRHR2) has been reported which is highly expressed in regions of rat brain that regulate attention and learning, arousal, sleep and processing of sensory information. The TRHR1 predominates in limbic structures involved in regulation of mood and in pituitary. This study examined the possibility that some of the newly discovered TRH-like peptides bind with high affinity to TRHR2, and that this receptor acts as the transducer for some of the CNS effects of this new class of neuropeptides. EEP, Val(2)-TRH and Leu(2)-TRH were analeptics, like TRH, but Phe(2)-TRH and Tyr(2)-TRH were not. The affinity and efficacy of TRH-like peptides for TRHR1 and TRHR2 were measured in HEK293 cells stably expressing these receptors. The IC(50) values of TRH-like peptides for displacement of [3H]TRH from TRHR2 were TRH<(Leu(2)-, Phe(2)-TRH)<(Gln(2)-, Ser(2)-TRH)<(Val(2)-, Tyr(2)-, Arg(2)-, Thr(2)-, and Glu(2)-TRH). The IC(50) for Leu(2)-TRH was about 100 times that for TRH. When tested at the calculated IC(50) values, TRH-like peptides stimulated calcium responses in cells expressing TRHR1 and TRHR2, indicating that the peptides act as weak agonists at both receptors. These results indicate that TRHR1 and TRHR2 do not mediate the behavioral effects of TRH-like peptides.     

Splenic infarct during infectious mononucleosis

We present a case of splenic infarct during infectious mononucleosis in a 17-y-old boy. The patient's condition improved without the need for surgery.     

Reduction in fear of falling through intense tai chi exercise training in older, transitionally frail adults

OBJECTIVES: To determine whether an intense tai chi exercise program could reduce fear of falling better than a wellness education (WE) program in older adults who had fallen previously and meet criteria for transitioning to frailty. DESIGN: Cluster-randomized, controlled trial of 48 weeks' duration. SETTING: Ten matched pairs of congregate living facilities in the greater Atlanta area. PARTICIPANTS: Sample of 291 women and 20 men, aged 70 to 97. MEASUREMENTS: Activity-related fear of falling using the Activities-Specific Balance Confidence Scale (ABC) and the Fall Efficacy Scale at baseline and every 4 months for 1 year. Demographics, time to first fall and all subsequent falls, functional measures, Centers for Epidemiologic Studies Depression Scale, medication use, level of physical activity, comorbidities, and adherence to interventions. RESULTS: Mean ABC was similar in both cohort groups at the time of randomization but became significantly higher (decreased fear) in the tai chi cohort at 8 months (57.9 vs 49.0, P<.001) and at study end (59.2 vs 47.9, P<.001). After adjusting for covariates, the mean ABC after 12 months of intervention was significantly greater in the tai chi group than in the WE group, with the differences increasing with time (mean difference at 12 months=9.5 points, 95% confidence interval=4.8-14.2, P<.001). CONCLUSION: Tai chi led to a significantly greater reduction in fear of falling than a WE program in transitionally frail older adults. The mean percentage change in ABC scores widened between tai chi and WE participants over the trial period. Tai chi should be considered in any program designed to reduce falling and fear of falling in transitionally frail older adults.     

The interface between stroke and infectious disease: Infectious diseases leading to stroke and infections complicating stroke

It is well established that several infectious diseases can directly lead to ischemic or hemorrhagic stroke during their course. It appears possible that common viral and bacterial infections can increase the susceptibility to stroke by promoting atherosclerosis, inflammation, and local thrombosis. Stroke commonly leads to disruption of protective mechanisms against infection and induces a cascade of anti-inflammatory and immunosuppressive reactions, which greatly increases the risk of infection. The social and economic costs of post-stroke infections and their impact on stroke morbidity and outcome are dramatic. Understanding the pathophysiologic links between stroke and infection is therefore of paramount importance, and effective preventive strategies to reduce the risk of infection are needed. This article summarizes current clinical and experimental data regarding the interactions between stroke and infection and outlines possible targets for therapeutic intervention.