Brain-derived neurotrophic factor (BDNF) modulates inhibitory, but not excitatory, transmission in the CA1 region of the hippocampus

Brain-derived neurotrophic factor (BDNF) modulates inhibitory, but not excitatory, transmission in the CA1 region of the hippocampus. J. Neurophysiol. 80: 3383-3386, 1998. Brain-derived neurotrophic factor (BDNF) has been reported to have rapid effects on synaptic transmission in the hippocampus. We report here that bath application of BDNF causes a small but significant decrease in stimulus-evoked inhibitory postsynaptic currents (IPSCs) on CA1 pyramidal cells, which is prevented by the tyrosine kinase inhibitor lavendustin A. BDNF causes a decrease in the 1/CV2 of the IPSC, and also reduces paired-pulse depression of the IPSC, suggesting a presynaptic site of action. In contrast, BDNF did not have a detectable effect on field excitatory postsynaptic potentials measured in stratum radiatum. We conclude that BDNF has a selective depressant action on inhibitory transmission in the hippocampus, due at least in part to a presynaptic mechanism.     

Physician judgments of chronic pain patients

Recent evidence has indicated that physician judgments of patients can be influenced by contextual factors. This study examined three contextual factors relevant to hypothetical patients with low back pain, using vignettes that were varied in a 2 x 2 x 2 factorial design: level of reported pain (high vs low), level of supporting medical evidence (high vs low), and the valence of the physician-patient interaction (positive vs negative). Perceived levels of pain, disability, emotional distress, and somatic preoccupation were rated by internists after reading a vignette. Ratings of pain and disability were lower for patients without supporting medical evidence; ratings of distress, somatic preoccupation, and disability were greater for patients who exhibited negative rather than positive affect; internist ratings of pain were lower than patient ratings among patients reporting high levels of pain, while ratings were inflated for patients with low levels of pain. The results suggest that characteristics of both the patient and the situation may influence medical judgments.     

Preservation of myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest with 2, 3-butanedione monoxime

One proposed contributory mechanism for depressed ventricular performance after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellular calcium homeostasis. Because 2,3-butanedione monoxime decreases intracellular calcium transients, this study tested the hypothesis that 2,3-butanedione monoxime supplementation of the hyperkalemic cardioplegic solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyte shortening were measured after 2 hours of incubation under normothermic conditions (37 degrees C, standard medium), hypothermic, hyperkalemic cardioplegic arrest (4 degrees C in Ringer's solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedione monoxime). Because beta-adrenergic agonists are commonly employed after cardioplegic arrest, myocyte contractile function was examined in the presence of the beta-agonist isoproterenol (25 nmol/L). Hypothermic, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplementation with 2,3 butanedione monoxime normalized myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Although beta-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperkalemic cardioplegic arrest, contractile function of myocytes exposed to beta-agonist after hypothermic, hyperkalemic cardioplegic arrest remained significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored beta-adrenergic responsiveness of myocytes after hypothermic, hyperkalemic cardioplegic arrest. Thus, supplementation of a hyperkalemic cardioplegic solution with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and beta-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-butanedione monoxime includes modulation of intracellular calcium transients or alterations in sensitivity to calcium. Supplementation with 2,3-butanedione monoxime may have clinical utility in improving myocardial contractile function after hypothermic, hyperkalemic cardioplegic arrest.     

Writer's cramp--a focal dystonia: etiology, diagnosis, and treatment

The complaint of hand cramps is common among patients who consult the neurologist or the hand surgeon. Classic writer's cramp is best characterized as a focal dystonia, and electromyographic studies reveal a characteristic pattern of cocontraction of the agonist and antagonist muscles of the forearm and hand. Although the outcome of treatment in the past has been unsatisfying, recent experience with new pharmacologic therapy, such as injections of botulinum toxin, has produced promising results. Further experience and improvement in this area will likely increase the therapeutic success in the treatment of writer's cramp and other focal dystonias.     

The prospective relationships between smoking and weight in a young, biracial cohort: the Coronary Artery Risk Development in Young Adults Study

This study examined the relationship between smoking status and weight change from baseline to Year 7 in a large biracial cohort, the Coronary Artery Risk Development in Young Adults study. Unadjusted for covariates, only male smokers weighed less than nonsmokers, with no effect among women. Adjusted for covariates, male and female smokers weighed less than nonsmokers at baseline, adjusted for age, total energy intake, alcohol intake, and physical fitness. Over the 7-year follow-up, all smoking status groups gained weight, including continuous smokers and initiators. Weight gain was greatest among those who quit smoking. Weight gain attributable to smoking cessation was 4.2 kg for Whites and 6.6 kg for Blacks. Smoking had a small weight-attenuating effect on Blacks. No such effects, however, were observed among Whites. These results suggest, at least in younger smokers, that smoking has minimal impact on body weight.     

The C-terminal domains of gammaS-crystallin pair about a distorted twofold axis

The 2-domain gammaS-crystallin, a highly conserved early evolutionaryoff-shoot of the gamma-crystallin family, is located in the water-richregion of eye lenses. The expressed C-terminal domain, gammaS-C, has beencrystallized and the 2.56 A X-ray structure determined. There are twodomains in the asymmetric unit which pair about a distorted twofold axis.One of the domains has an altered conformation in a highly conserved regionof the protein, the tyrosine corner. The distorted gammaS-C dimer ofdomains is compared with the highly symmetrical, equivalent recombinantdimer of C-terminal domains from gammaB- crystallin. Sequence changes closeto the interface, that distinguish gammaS from the other gamma-crystallins,are examined in order to evaluate their role in symmetrical domain pairing.     

Modulation of synaptic transmission by dopamine and norepinephrine in ventral but not dorsal striatum

Although the ventral striatum (nucleus accumbens; NAc) and dorsal striatum are associated with different behaviors, these structures are anatomically and physiologically similar. In particular, dopaminergic afferents from the midbrain appear to be essential for the normal functioning of both nuclei. Although a number of studies have examined the effects of dopamine on the physiology of NAc or striatal cells, results have varied, and few studies have compared directly the actions of dopamine on both of these nuclei. Here we use slice preparations of the NAc and dorsal striatum to compare how synaptic transmission in these nuclei is modulated by catecholamines. As previously reported, dopamine depressed excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) in the NAc. Surprisingly, however, neither EPSPs nor IPSPs in the dorsal striatum were affected by dopamine. Similarly, norepinephrine depressed excitatory synaptic transmission in the NAc by an alpha-adrenergic receptor-dependent mechanism but was without effect on excitatory transmission in the dorsal striatum. Inhibitory synaptic transmission was not affected by norepinephrine in either structure. These results suggest that the functional roles of dopamine and norepinephrine are not the same in the dorsal striatum and the NAc.