Actions of N-arachidonyl-glycine in a rat neuropathic pain model.

While cannabinoid receptor agonists reduce the abnormal pain sensations associated with animal models of neuropathic pain states they also produce CB(1) receptor mediated side effects. Recently, a number of arachidonic acid-amino acid conjugates, including N-arachidonyl-glycine (NAGly), have been identified which are structurally related to the endocannabinoid arachidonyl ethanolamide (anandamide). In the present study we examined the effect of NAGly in a rat model of neuropathic pain.

Design of surface electrode array for measuring conduction velocity in the human genioglossus muscle.

A new appliance, incorporating linear arrays of pin electrodes for genioglossus (GG) surface electromyography measurement, is presented. This design enables the estimation of GG muscle fiber conduction velocity, which decreases with fatigue. The performance of the device was evaluated for ten healthy human subjects during fatiguing and force varying contractions.

muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits.

The tetrodotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that muO-conotoxin MrVIB from Conus marmoreus displays substantial selectivity for Na(v)1.

Non-random fluctuations in power output during self-paced exercise.

Objectives: To analyse the power output measured during a self-paced 20-km cycling time trial, during which power output was free to vary, in order to assess the level and characteristics of the variability in power output that occurred during the exercise bout.

Methods: Eleven well-trained cyclists performed a 20-km cycling time trial, during which power output was sampled every 200 m. Power spectrum analysis was performed on the power output data, and a fractal dimension was calculated for each trial using the Higuchi method.

Effects of oral preload, CCK or bombesin administration on short term food intake of melanocortin 4-receptor knockout (MC4RKO) mice.

We investigated whether either heterozygous (HET) or homozygous (knockout, KO) disruption of the melanocortin type 4 receptor (MC4R) gene alters post ingestive responsiveness of mice. Specifically, we tested the hypothesis that hyperphagia in MC4RKO mice might be due to a deficit in processes that sustain intermeal intervals (satiety) and/or processes that terminate ongoing episodes of eating (satiation). To test satiety, mice drank an oral preload and then we monitored intake of a subsequent liquid diet test meal.

Structure of an Hsp90-Cdc37-Cdk4 complex.

Activation of many protein kinases depends on their interaction with the Hsp90 molecular chaperone system. Recruitment of protein kinase clients to the Hsp90 chaperone system is mediated by the cochaperone adaptor protein Cdc37, which acts as a scaffold, simultaneously binding protein kinases and Hsp90. We have now expressed and purified an Hsp90-Cdc37-Cdk4 complex, defined its stoichiometry, and determined its 3D structure by single-particle electron microscopy.

Food motivated behavior of melanocortin-4 receptor knockout mice under a progressive ratio schedule.

Melanocortin-4 receptor knockout (MC4RKO) mice are hyperphagic and develop obesity under free feeding conditions. We reported previously that MC4RKO mice did not maintain hyperphagia and as a result lost weight when required to press a lever to obtain food on a fixed ratio procurement schedule. To assess the generality of this result, we tested MC4RKO mice and their heterozygous and wild type littermates using progressive ratio (PR) schedules that are believed to be sensitive indicators of motivation.

Automatic detection of gait events using kinematic data.

The timing of heel strike (HS) and toe off (TO), the events that mark the transitions between stance and swing phase of gait, is essential when analysing gait. Force plate recordings are routinely used to identify these events. Additional instrumentation, such as force sensitive resistors, can also been used.

A brain-behaviour initiative for South Africa: the time is right.

Background: Many have advocated for science and health research in developing world settings. However, there has been less focus on the value of basic and clinical neuroscience research in this context. The current paper focuses on the relevance of a brain-behaviour research initiative in South Africa.

The association of lead exposure and motor performance mediated by cerebral white matter change.

The goals were to determine if lead exposure is associated with cerebral white matter changes (WMC) and if so, does WMC mediate the relation between lead and psychomotor slowing as measured by Grooved Pegboard (GP). In the literature, age is the strongest predictor of WMC and therefore 61 lead smelter workers age 50 and under were included in the study population. Mean (range) age was 40 (23-50) years, years of education was 9 (0-13), duration of employment was 19 (1-26), current blood lead (PbB) was 29 (16-42) microg/dl, working lifetime weighted integrated blood lead (IBL) was 826 (65-1451) microg year/dl, working lifetime weighted average blood lead (TWA) was 42 (17-59) microg/dl, and bone lead (PbBn) was 39 (-12-90) microg Pb/g bone mineral.

Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex.

Hsp90 (heat shock protein of 90 kDa) is a ubiquitous molecular chaperone responsible for the assembly and regulation of many eukaryotic signalling systems and is an emerging target for rational chemotherapy of many cancers. Although the structures of isolated domains of Hsp90 have been determined, the arrangement and ATP-dependent dynamics of these in the full Hsp90 dimer have been elusive and contentious. Here we present the crystal structure of full-length yeast Hsp90 in complex with an ATP analogue and the co-chaperone p23/Sba1.

Retrograde signalling by endocannabinoids.

The cannabinoid neurotransmitter system comprises cannabinoid G protein-coupled membrane receptors (CB1 and CB2), endogenous cannabinoids (endocannabinoids), as well as mechanisms for their synthesis, membrane transport and metabolism. Within the brain the marijuana constituent delta9-tetrahydrocannabinol (THC) produces its pharmacological actions by acting on cannabinoid CB1 receptors. THC modulates neuronal excitability by inhibiting synaptic transmission via presynaptic CB1-mediated mechanisms.

Knee movement patterns of injured and uninjured adolescent basketball players when landing from a jump: a case-control study.

Background: A common knee injury mechanism sustained during basketball is landing badly from a jump. Landing is a complex task and requires good coordination, dynamic muscle control and flexibility. For adolescents whose coordination and motor control has not fully matured, landing badly from a jump can present a significant risk for injury.

Subjective report versus objective measurement of activities of daily living in Parkinson's disease.

We compared subjective self-reports with objective performance ratings of activities of daily living (ADLs) and instrumental ADLs (IADLs) in patients with Parkinson's disease (PD) and identified variables associated with discordance of ratings between these two methods. Seventy-six PD patients completed a modified Older Americans Resources and Services scale, assessing ADLs and IADLs. These results were compared with structured performance tests of walking, eating, dressing, money, and medicine management administered in the clinic.

Differences in lower limb transverse plane joint moments during gait when expressed in two alternative reference frames.

When comparing previous studies that have measured the three-dimensional moments acting about the lower limb joints (either external moments or opposing internal joint moments) during able-bodied adult gait, significant variation is apparent in the profiles of the reported transverse plane moments. This variation cannot be explained on the basis of adopted convention (i.e.

Seizure versus syncope.

One of the most common but difficult management problems in medicine is that of patients who present with a paroxysmal loss of consciousness. All too often the underlying diagnosis remains elusive. This has a cost both in terms of mortality and ongoing morbidity and in terms of the financial burden associated with hospitalisation and repeated investigations.

Stressed-out endogenous cannabinoids relieve pain.

A variety of physical and psychological stressors induce analgesia by activating descending systems that project from the brain to the spinal cord. This stress-induced analgesia (SIA) is mediated by distinct opioid- and non-opioid-dependent mechanisms. New evidence suggests that non-opioid SIA is mediated by two independent endocannabinoids within the midbrain.

Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models.

While cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central CB(1) receptor-mediated motor and psychotropic side effects. The actions of endocannabinoids, such as anandamide are terminated by removal from the extracellular space, then subsequent enzymatic degradation by fatty-acid amide hydrolase (FAAH). In the present study, we compared the effect of a selective FAAH inhibitor, URB597, to that of a pan-cannabinoid receptor agonist HU210 in rat models of chronic inflammatory and neuropathic pain.

Effect of lead exposure and ergonomic stressors on peripheral nerve function.

In this study we investigated the effect of recent and chronic lead exposure, and its interaction with ergonomic stressors, on peripheral nerve function. In a cross-sectional design, we used retrospective exposure data on 74 primary lead smelter workers. We measured blood and bone lead levels and, from historical records, calculated lead dose metrics reflecting cumulative lead exposure: working-lifetime integrated blood lead (IBL) and working-lifetime weighted-average blood lead (TWA).

Depression in adults with type 2 diabetes: the role of adherence, body mass index, and self-efficacy.

Considerable evidence links depression with the development and worsening of diabetes, but the factors contributing to this link have not been established. The authors examined the role of adherence, body mass index (BMI), and self-efficacy. Adult patients with Type 2 diabetes (N = 56) completed self-report measures of diet and exercise adherence, diet and exercise self-efficacy, and depression.