Targeting the post-synaptic proteome has therapeutic potential for psychosis in Alzheimer Disease.

Individuals with Alzheimer Disease who develop psychotic symptoms (AD + P) experience more rapid cognitive decline and have reduced indices of synaptic integrity relative to those without psychosis (AD-P). We sought to determine whether the postsynaptic density (PSD) proteome is altered in AD + P relative to AD-P, analyzing PSDs from dorsolateral prefrontal cortex of AD + P, AD-P, and a reference group of cognitively normal elderly subjects. The PSD proteome of AD + P showed a global shift towards lower levels of all proteins relative to AD-P, enriched for kinases, proteins regulating Rho GTPases, and other regulators of the actin cytoskeleton. We computationally identified potential novel therapies predicted to reverse the PSD protein signature of AD + P. Five days of administration of one of these drugs, the C-C Motif Chemokine Receptor 5 inhibitor, maraviroc, led to a net reversal of the PSD protein signature in adult mice, nominating it as a novel potential treatment for AD + P.

G protein ßγ subunits play a critical role in the actions of amphetamine.

Abnormal levels of dopamine (DA) are thought to contribute to several neurological and psychiatric disorders including drug addiction. Extracellular DA levels are regulated primarily via reuptake by the DA transporter (DAT). Amphetamine, a potent psychostimulant, increases extracellular DA by inducing efflux through DAT. Recently, we discovered that G protein ßγ subunits (Gßγ) interact with DAT, and that in vitro activation of Gßγ promotes DAT-mediated efflux. Here, we investigated the role of Gßγ in the actions of amphetamine in DA neurons in culture, ex vivo nucleus accumbens (NAc), and freely moving rats. Activation of Gßγ with the peptide myr-Ser-Ile-Arg-Lys-Ala-Leu-Asn-Ile-Leu-Gly-Tyr-Pro-Asp-Tyr-Asp (mSIRK) in the NAc potentiated amphetamine-induced hyperlocomotion, but not cocaine-induced hyperlocomotion, and systemic or intra-accumbal administration of the Gßγ inhibitor gallein attenuated amphetamine-induced, but not cocaine-induced hyperlocomotion. Infusion into the NAc of a TAT-fused peptide that targets the Gßγ-binding site on DAT (TAT-DATct1) also attenuated amphetamine-induced but not cocaine-induced hyperlocomotion. In DA neurons in culture, inhibition of Gßγ with gallein or blockade of the Gßγ-DAT interaction with the TAT-DATct1 peptide decreased amphetamine-induced DA efflux. Furthermore, activation of Gßγ with mSIRK potentiated and inhibition of Gßγ with gallein reduced amphetamine-induced increases of extracellular DA in the NAc in vitro and in freely moving rats. Finally, systemic or intra-accumbal inhibition of Gßγ with gallein blocked the development of amphetamine-induced, but not cocaine-induced place preference. Collectively, these results suggest that interaction between Gßγ and DAT plays a critical role in the actions of amphetamine and presents a novel target for modulating the actions of amphetamine in vivo.

Cervical spine injuries and their neurologic implications.

This article presents the neurologic implications of cervical spine injuries by reviewing (1) cervical spine anatomy, (2) initial patient evaluation, (3) the type of neurologic injuries that can occur, (4) the treatment of athletes with these injuries, and (5) criteria for returning to activity.

Cervical spine fractures in athletes.

This article presents (1) the on-field assessment of the athlete who has sustained a cervical injury, (2) the diagnostic modalities necessary to make an accurate diagnosis, (3) the specific fractures/dislocations seen in the cervical spine, and (4) the guidelines used to determine if the athlete may return to active competition.

A prospective, randomized, double-blind evaluation of trigger-point injection therapy for low-back pain.

The efficacy of trigger-point injection therapy in treatment of low-back strain was evaluated in a prospective, randomized, double-blind study. The patient population consisted of 63 individuals with low-back strain. Patients with this diagnosis had nonradiating low-back pain, normal neurologic examination, absence of tension signs, and lumbosacral roentgenograms interpreted as being within normal limits. They were treated conservatively for 4 weeks before entering the study. Injection therapy was of four different types: lidocaine, lidocaine combined with a steroid, acupuncture, and vapocoolant spray with acupressure. Results indicated that therapy without injected medication (63% improvement rate) was at least as effective as therapy with drug injection (42% improvement rate), at a P value of 0.09. Trigger-point therapy seems to be a useful adjunct in treatment of low-back strain. The injected substance apparently is not the critical factor, since direct mechanical stimulus to the trigger-point seems to give symptomatic relief equal to that of treatment with various types of injected medication.

Efficacy of cortisone injection in treatment of trigger fingers and thumbs.

One hundred eight trigger fingers and thumbs in 74 consecutive patients were treated by injections of triamcinalone and followed for an average of 3 1/2 years. Minimum follow-up was 1 year. Eighty four percent of trigger fingers and 92% of trigger thumbs were cured with a single injection, and a repeat injection for treatment of recurrent symptoms raised these figures to 91% and 97%, respectively. All injections were done by one physician. There were no complications. We conclude that intrasynovial injection of a steroid compound is the appropriate initial treatment for trigger fingers and thumbs.

Low back pain in the competitive tennis player.

The etiologies of low back pain and the biomechanics and pathology of the lumbar spine as they relate to tennis stroke mechanics have been reviewed, and a treatment protocol has been presented. A recent survey of the Men's Professional Tennis Tour is the only article found that discusses low back pain in tennis players; the orthopaedic and sports medicine literature is otherwise devoid of any relevant studies. Because this one survey indicates that 38 per cent of 143 tennis players missed at least one tournament because of low back problems, it seems obvious that an epidemiologic study on low back pain in racquet sports is vital to a more thorough understanding of the problem.

The effect of cryosurgery and polymethylmethacrylate in dogs with experimental bone defects comparable to tumor defects.

The effects of liquid nitrogen (LN) and polymethylmethacrylate (PMMA) on normal bone, bone graft incorporation, and reossification were evaluated by simulating a tumor in dogs with experimental bone cavity. Ten skeletally mature mongrel dogs (20 femora) were divided into three groups: Group I, controls; Group II, LN (with and without bone graft); and Group III, PMMA (with and without LN). Roentgenograms, whole-mount histology, and tetracycline fluorescence studies were performed on the distal femur. Correlation of these studies showed that (1) marked trabecular and bone necrosis, extending 7-12 mm around the circumference of the cavity, developed by three and seven weeks after LN but no bony necrosis occurred after PMMA; (2) the pattern of reossification following cryosurgery was delayed and abnormal, demonstrating increased calcification and metaplastic bone formation; (3) cryosurgery decreased the rate of bone graft incorporation; (4) the cryonecrotic rim following cryosurgery correlated with an abortive attempt at peripheral reossification; and (5) cryosurgery had no effect on the articular cartilage. Cryosurgery is effective in causing bone necrosis, whereas PMMA is not, and the pattern of reossification is delayed and altered by freezing. This study suggests that microvascular thrombosis with subsequent ischemic infarction of bone is a major cause of bone necrosis following cryosurgery.