Visual guidance of the human foot during a step

When the intended foot placement changes during a step, either due to an obstacle appearing in our path or the sudden shift of a target, visual input can rapidly alter foot trajectory. However, previous studies suggest that when intended foot placement does not change, the path of the foot is fixed after it leaves the floor and vision has no further influence. Here we ask whether visual feedback can be used to improve the accuracy of foot placement during a normal, unperturbed step. To investigate this we measured foot trajectory when subjects made accurate steps, at fast and slow speeds, to stationary floor-mounted targets. Vision was randomly occluded in 50% of trials at the point of foot-off. This caused an increase in foot placement error, reflecting lower accuracy and higher variability. This effect was greatest for slow steps. Trajectory heading analysis revealed that visually guided corrections occurred as the foot neared the target (on average 64 mm away). They occurred closer to the target for the faster movements thus allowing less time and space to execute corrections. However, allowing for a fixed reaction time of 120 ms, movement errors were detected when the foot was approximately halfway to the target. These results suggest that visual information can be used to adjust foot trajectory during the swing phase of a step when stepping onto a stationary target, even for fast movements. Such fine control would be advantageous when environmental constraints place limitations on foot placement, for example when hiking over rough terrain.     

Long-acting beta 2-adrenoceptor agonists: a new perspective in the treatment of asthma.

New long-acting beta 2-adrenoceptor agonists, formoterol and salmeterol, may soon appear in several European countries for treatment of asthma. This review examines currently available information and compares the basic pharmacology and describes the clinical effects of these new drugs. The long duration of bronchodilation seen in clinical studies seems to be similar, whereas in isolated tissues there might be a difference in the binding characteristics to the beta 2-adrenoceptor. Long-acting beta 2-agonists could have an inhibitory effect on inflammatory events related to asthma, but the clinical relevance of these effects is not clear at present. Long-term studies up to one year with both new drugs have not shown any unexpected side-effects, and no tachyphylaxis to beta-adrenoceptor stimulation has been reported. Patients appear to strongly prefer the new drugs compared to the short-acting beta 2-agonists. The potential place for these drugs in the treatment of asthma is discussed and some pitfalls pointed out. It is likely that the long-acting beta 2-agonists will be beneficial to many asthmatic patients.     

Pharmacologic treatment of schizophrenia.

The literature on the pharmacologic treatment of schizophrenia and schizoaffective disorders is reviewed (116 references). All clinically active antipsychotic drugs share the ability to block postsynaptic dopamine receptors in the central nervous system. Their potencies vary, chlorpromazine and thioridazine being the least potent and fluphenazine and haloperidol the most potent. The adverse effects of the neuroleptics include acute dystonia, parkinsonian symptoms (extrapyramidal symptoms), akathisia, tardive dyskinesia, and tardive dystonia. When used at equipotent doses, all classic neuroleptics now available are equally effective in the treatment of schizophrenia. Choice of drug is based on adverse effects and patient response. The neuroleptics are effective in most acute exacerbations of schizophrenia and for the prevention or mitigation of relapse. Their effects are more pronounced on the positive symptoms of schizophrenia, such as hallucinations, delusions, disordered thinking, and paranoia, than on the negative symptoms, such as deficits in social interaction, emotional expression, and motivation. Strategies for acute and maintenance treatment and for the management of treatment-resistant patients are reviewed. The pharmacology and clinical use of the newer atypical neuroleptics, particularly clozapine, and their adverse effects are discussed.     

Charge immobilization of the voltage sensor in domain IV is independent of sodium current inactivation

Recovery from fast inactivation in voltage-dependent Na⁺ channels is associated with a slow component in the time course of gating charge during repolarization (i.e. charge immobilization), which results from the slow movement of the S4 segments in domains III and IV (S4-DIII and S4-DIV). Previous studies have shown that the non-specific removal of fast inactivation by the proteolytic enzyme pronase eliminated charge immobilization, while the specific removal of fast inactivation (by intracellular MTSET modification of a cysteine substituted for the phenylalanine in the IFM motif, ICM_MTSET, in the inactivation particle formed by the linker between domains III and IV) only reduced the amount of charge immobilization by nearly one-half. To investigate the molecular origin of the remaining slow component of charge immobilization we studied the human cardiac Na⁺ channel (hH1a) in which the outermost arginine in the S4-DIV, which contributes ∼20% to total gating charge ( Q _max), was mutated to a cysteine (R1C-DIV). Gating charge could be fully restored in R1C-DIV by exposure to extracellular MTSEA, a positively charged methanethiosulphonate reagent. The RIC-DIV mutation was combined with ICM_MTSET to remove fast inactivation, and the gating currents of R1C-DIV-ICM_MTSET were recorded before and after modification with MTSEA_o. Prior to MTSEA_o, the time course of the gating charge during repolarization ( off -charge) was best described by a single fast time constant. After MTSEA, the off -charge had both fast and slow components, with the slow component accounting for nearly 35% of Q _max. These results demonstrate that the slow movement of the S4-DIV during repolarization is not dependent upon the normal binding of the inactivation particle.     

The influence of lycopene on the proliferation of human breast cell line (MCF-7).

Lycopene, a non-provitaminic carotenoid, present in many fruit and vegetables, such as tomatoes and their processed products, has been associated with decreased risk of chronic diseases including cancer. The influence of lycopene on the proliferation of the breast tumour cell line (MCF-7) was tested using MTT and BrdU assays at different time intervals (from 24 to 72h) and dose-response (from 0.125 to 100muM). The induction of Gap Junction Intercellular Communication (GJIC) was evaluated by dye-transfer assay using Lucifer Yellow on monolayer cells treated with different lycopene concentrations (from 0.125 to 5muM) for 6 to 48h. The Minimal Inhibitory Concentration (MIC) of lycopene was of 5muM, after a 24h exposure. A prolonged exposure time (72h) induced a similar inhibitory effect. Lycopene stimulated the functionality of GJIC at concentrations of 1muM after 24h and this effect was dose-dependent. The induction of GJIC by lycopene was confirmed by an increased expression of connexin 43. Collectively, the above data confirm the inhibitor effects of lycopene on MCF-7 cell growth and suggest that lycopene is involved in the modulation of the gap junction intercellular communication in this cell line, as observed for other cancer cell lines.