Medical Library

Striatal neurons encoded temporal information in duration discrimination task.

To clarify the roles of the basal ganglia in time perception, single-unit activity was recorded from both sides of the striatum of a monkey performing a duration discrimination task. In the task, two visual cues were presented successively in different durations (0.2 approximately 1.6 s). Each cue presentation was followed by a 1-s delay period. The subject was instructed to choose a longer presented cue after the second delay period. There were two types of trials for sequence of cue duration, the long-short (LS) trials in which the first cue (C1) was longer than the second cue (C2) and the short-long (SL) trials in which the C1 was shorter than the C2. Striatal neurons phasically responded during the first delay (D1) and second delay (D2) periods. Responses during the D1 period changed depending on C1 duration. Activity of populations of D1-response neurons correlated with C1 duration positively or negatively. Responses during the D2 period differed between the LS and SL trials. Activity of population of D2-response neurons also changed depending on C2 duration. But the dependence on C2 duration was affected by the trial type, that is, whether the C2 was longer or shorter compared to the C1.These findings suggest that striatal neurons could encode cue durations with monotonically changing responses in the D1 period and discrimination results between the two cue durations in the D2 period.

Chiba A, Oshio KI, Inase M.

Department of Physiology, Kinki University School of Medicine, Ohno-Higashi 377-2, Osaka-Sayama, Osaka, 589-8511, Japan, kchiba@med.kindai.ac.jp.

Audio-vocal system regulation in children with autism spectrum disorders.

Do children with autism spectrum disorders (ASD) respond similarly to perturbations in auditory feedback as typically developing (TD) children? Presentation of pitch-shifted voice auditory feedback to vocalizing participants reveals a close coupling between the processing of auditory feedback and vocal motor control. This paradigm was used to test the hypothesis that abnormalities in the audio-vocal system would negatively impact ASD compensatory responses to perturbed auditory feedback. Voice fundamental frequency (F (0)) was measured while children produced an /a/ sound into a microphone. The voice signal was fed back to the subjects in real time through headphones. During production, the feedback was pitch shifted (-100 cents, 200 ms) at random intervals for 80 trials. Averaged voice F (0) responses to pitch-shifted stimuli were calculated and correlated with both mental and language abilities as tested via standardized tests. A subset of children with ASD produced larger responses to perturbed auditory feedback than TD children, while the other children with ASD produced significantly lower response magnitudes. Furthermore, robust relationships between language ability, response magnitude and time of peak magnitude were identified. Because auditory feedback helps to stabilize voice F (0) (a major acoustic cue of prosody) and individuals with ASD have problems with prosody, this study identified potential mechanisms of dysfunction in the audio-vocal system for voice pitch regulation in some children with ASD. Objectively quantifying this deficit may inform both the assessment of a subgroup of ASD children with prosody deficits, as well as remediation strategies that incorporate pitch training.

Russo N, Larson C, Kraus N.

The Roxelyn and Richard Pepper Department of Communication Sciences, Northwestern University, Frances Searle Bldg, 2240 Campus Drive, Evanston, IL, 60208, USA, n-russo@northwestern.edu.

Pedunculopontine nucleus microelectrode recordings in movement disorder patients.

The pedunculopontine nucleus (PPN) lies within the brainstem reticular formation and is involved in the motor control of gait and posture. Interest has focused recently on the PPN as a target for implantation of chronic deep brain stimulation (DBS) electrodes for Parkinson\’s disease (PD) and progressive supranuclear palsy (PSP) therapy. The aim of this study was to examine the neurophysiology of the human PPN region and to identify neurophysiological landmarks that may aid the proper placement of DBS electrodes in the nucleus for the treatment of PD and PSP. Neuronal firing and local field potentials were recorded simultaneously from two independently driven microelectrodes during stereotactic neurosurgery for implantation of a unilateral DBS electrode in the PPN in five PD patients and two PSP patients. Within the PPN region, the majority (57%) of the neurons fired randomly while about 21% of the neurons exhibited \’bursty\’ firing. In addition, 21% of the neurons had a long action potential duration and significantly lower firing rate suggesting they were cholinergic neurons. A change in firing rate produced by passive and/or active contralateral limb movement was observed in 38% of the neurons that were tested in the PPN region. Interestingly, oscillatory local field potential activity in the beta frequency range ( approximately 25 Hz) was also observed in the PPN region. These electrophysiological characteristics of the PPN region provide further support for the proposed role of this region in motor control. It remains to be seen to what extent the physiological characteristics of the neurons and the stimulation-evoked effects will permit reliable identification of PPN and determination of the optimal target for DBS therapy.

Weinberger M, Hamani C, Hutchison WD, Moro E, Lozano AM, Dostrovsky JO.

Department of Physiology, University of Toronto, Med Sci Bldg 3302, 1 King’s College Circle, M5S 1A8, Toronto, ON, Canada, moran.weinberger@utoronto.ca.

A microarray chip for label-free detection of narcotics.

A protein array chip for label-free optical detection of low molecular weight compounds has been developed. As a proof of principle, the chip is proven capable of rapidly (approximately 1 min) determining hits from aqueous cocktails composed of four common narcotics, cocaine, ecstasy, heroin, and amphetamine, using imaging surface plasmon resonance (SPR) as the detection principle. The chip is produced by injecting a mixture of antibodies and letting them self-sort and bind to narcotic analog coupled proteins already present in a predefined pattern on the supporting substrate. An indirect detection method, where antibodies are displaced from the surface upon recognition of their corresponding narcotics, is used to obtain the optical contrast and thus a detectable SPR and/or ellipsometric signal. Two types of readouts are possible from the present setup: intensity SPR images and SPR/ellipsometric sensorgrams. Positive hits were routinely obtained for analyte concentrations of 50 pg/muL and the limit of detection, without any parameter optimizations, seems to fall in the range 0.5 pg/muL (1.4 nM) for heroin, 2.5 pg/muL (8.2 nM) for cocaine, and 5 pg/muL for the other two narcotics (26 nM for ecstasy and 37 nM for amphetamine). With improved readout possibilities (sampling frequency), signal evaluation algorithms, and antibody-antigen design strategies, we believe this limit can be further improved. The chip is shown to work for many measurement cycles with excellent reproducibility. Moreover, with a more advanced fluidic system, excess injected antibodies could be collected and reused for many cycles, which could make the running costs of the system very low. The chip is in no way limited to detection of narcotics. Other low molecular weight compounds could easily be detected on the same chip. For example, trinitrotoluene detection has already been demonstrated using our chip. Possible areas of application for the system are therefore envisaged in airport and underground transport security, customs, drug interdiction, forensics, and as warning alerts on military equipment and personnel.

Klenkar G, Liedberg B.

Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.

Trends and opportunities in food pathogen detection.

Nugen SR, Baeumner AJ.

Department of Biological and Environmental Engineering, Cornell University, 318 Riley-Robb Hall, Ithaca, NY, 14853, USA.

Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core.

RATIONALE: Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine. OBJECTIVES: To extend previous findings of striatal hypersensitivity with behavioral observations and with cellular activity in the nucleus accumbens and prefrontal cortex in sensitized animals. MATERIALS AND METHODS: Rats treated acutely with 0, 1, 2.5, or 5 mg/kg i.p. amphetamine and sensitized rats challenged with 1 mg/kg i.p. amphetamine were scored for stereotypy, rearing, and grooming, and locomotor activity recorded. c-fos positive nuclei were quantified in the nucleus accumbens and prefrontal cortex after expression of sensitization with 1 mg/kg i.p. amphetamine. RESULTS: Intense stereotypy was seen in animals treated acutely with 5 mg/kg amphetamine, but not in the sensitized group treated with 1 mg/kg amphetamine. The c-fos response to amphetamine in the accumbens core was augmented in amphetamine-pretreated animals with a shift in the distribution of optical density, while no effect of sensitization was seen in the nucleus accumbens shell or prefrontal cortex. CONCLUSIONS: A lack of stereotypy in the sensitized group indicates a dissociation of behavioral responses to amphetamine and striatal immediate-early gene activation patterns. The increase in c-fos positive nuclei and shift in the distribution of optical density observed in the nucleus accumbens core suggests recruitment of a new population of neurons during expression of sensitization.

Nordquist RE, Vanderschuren LJ, Jonker AJ, Bergsma M, de Vries TJ, Pennartz CM, Voorn P.

Department of Anatomy and Neurosciences, Vrije Universiteit Medical Center, Amsterdam, The Netherlands, r.e.nordquist@uu.nl.

Phylogenetic diversity of nitrogen-fixing bacteria in mangrove sediments assessed by PCR-denaturing gradient gel electrophoresis.

Culture-independent PCR-denaturing gradient gel electrophoresis (DGGE) was employed to assess the composition of diazotroph species from the sediments of three mangrove ecosystem sites in Sanya, Hainan Island, China. A strategy of removing humic acids prior to DNA extraction was conducted, then total community DNA was extracted using the soil DNA kit successfully for nifH PCR amplification, which simplified the current procedure and resulted in good DGGE profiles. The results revealed a novel nitrogen-fixing bacterial profile and fundamental diazotrophic biodiversity in mangrove sediments, as reflected by the numerous bands present DGGE patterns. Canonical correspondence analysis (CCA) revealed that the sediments organic carbon concentration and available soil potassium accounted for a significant amount of the variability in the nitrogen-fixing bacterial community composition. The predominant DGGE bands were sequenced, yielding 31 different nifH sequences, which were used in phylogenetic reconstructions. Most sequences were from Proteobacteria, e.g. alpha, gamma, beta, delta-subdivisions, and characterized by sequences of members of genera Azotobacter, Desulfuromonas, Sphingomonas, Geobacter, Pseudomonas, Bradyrhizobium and Derxia. These results significantly expand our knowledge of the nitrogen-fixing bacterial diversity of the mangrove environment.

Zhang Y, Dong J, Yang Z, Zhang S, Wang Y.

South China Sea Institute of Oceanology, Chinese Academy of Sciences, 510301, Guangzhou, People’s Republic of China.

Influence of deposit stage and failed ESWT on the surgical results of arthroscopic treatment of calcifying tendonitis of the shoulder.

The purpose of the present study is the evaluation of a possible influence of the preoperative deposit stage, the postoperative deposit elimination and failed preoperative extracorporeal shockwave therapy on the surgical outcome of arthroscopic treatment of tendinosis calcarea. From 1997 to 2004, 65 patients underwent arthroscopic resection of calcific deposits of the shoulder after failed conservative treatment. Patients with rotator cuff tears, major cartilage damage, or previous surgery were excluded. Out of 50 patients 45 (17 men, 28 women) that could be contacted with a mean age of 49 +/- 8 years could be followed-up with a mean of 36 months (14-89) after surgery. A total of 24 patients (53.3%) underwent preoperative extracorporeal shock-wave therapy (ESWT). For the clinical evaluation the Constant and Murley Score, the Simple Shoulder Test, the Western Ontario Rotator Cuff Index (WORC) and visual analog scales for pain, function and satisfaction were used. For the radiological evaluation, the classifications according to Gaertner and Bosworth were used. Statistical analysis was done with the Wilcoxon test, the Mann-Whitney test and ANOVA. The Constant and Murley Score improved significantly from preoperative 63.5 +/- 11.4 to postoperative 93.9 +/- 9.9 points (P < .0001) at follow-up, the Simple Shoulder Test from 1.7 +/- 2 to 9.9 +/- 2.8 points (P < .0001), the WORC score from 1,591.2 +/- 337.4 to 345.4 +/- 392 points (P < .0001). The visual analog scales for pain, function and patient satisfaction also significantly improved (P < .0001). Preoperative radiological evaluation according to the Gaertner classification revealed 37 type I deposits, 6 type II and 2 type III deposits; postoperative no calcific deposits were seen in 37 patients, 6 type I and 2 type III deposits. According to the Bosworth classification 13 type I, 19 type II and 13 type III deposits were seen preoperatively. Postoperative X-rays showed 6 type I and 1 type II and III deposits. There was no significant correlation of the clinical results with the pre- or postoperative findings. The 24 patients who underwent ESWT before surgery did not show significantly better results than patients without ESWT. In conclusion, arthroscopic removal of calcific deposits of the shoulder shows good clinical results for pain reduction, shoulder function and patient satisfaction. The type of calcific deposit and the preoperative treatment of the shoulder with ESWT did not have any significant impact on the postoperative results.

Lorbach O, Kusma M, Pape D, Kohn D, Dienst M.

Department of Orthopaedic Surgery, Saarland University, Kirrberger Strasse, 66421, Homburg/Saar, Germany, olaf.lorbach@gmx.de.

What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium?

Microalbuminuria is an important risk factor for cardiovascular disease and progressive renal impairment. This holds true in the general population and particularly in those with diabetes, in whom it is common and marks out those likely to develop macrovascular disease and progressive renal impairment. Understanding the pathophysiological mechanisms through which microalbuminuria occurs holds the key to designing therapies to arrest its development and prevent these later manifestations.Microalbuminuria arises from the increased passage of albumin through the glomerular filtration barrier. This requires ultrastructural changes rather than alterations in glomerular pressure or filtration rate alone. Compromise of selective glomerular permeability can be confirmed in early diabetic nephropathy but does not correlate well with reported glomerular structural changes. The loss of systemic endothelial glycocalyx-a protein-rich surface layer on the endothelium-in diabetes suggests that damage to this layer represents this missing link. The epidemiology of microalbuminuria reveals a close association with systemic endothelial dysfunction and with vascular disease, also implicating glomerular endothelial dysfunction in microalbuminuria.Our understanding of the metabolic and hormonal sequelae of hyperglycaemia is increasing, and we consider these in the context of damage to the glomerular filtration barrier. Reactive oxygen species, inflammatory cytokines and growth factors are key players in this respect. Taken together with the above observations and the presence of generalised endothelial dysfunction, these considerations lead to the conclusion that glomerular endothelial dysfunction, and in particular damage to its glycocalyx, represents the most likely initiating step in diabetic microalbuminuria.

Satchell SC, Tooke JE.

Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK, s.c.satchell@bristol.ac.uk.

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles.

AIMS/HYPOTHESIS: Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones. METHODS: We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography. RESULTS: There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol. CONCLUSIONS/INTERPRETATION: Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol. Trials Registry no.: ISRCTN 76558770.

Swaminathan K, Davies J, George J, Rajendra NS, Morris AD, Struthers AD.

Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK, krishnan.swaminathan@nhs.net.