Myositis specific autoantibodies as a new diagnostic criterion for idiopathic inflammatory myopathies

Myositis specific autoantibodies (MSA) are the most specific diagnostic criteria for idiopathic inflammatory myopathies (IIM). There is no evidence of MSA presence in patients with other neuromuscular or connective tissue diseases. MSA are associated with homogeneous clinical syndromes: antisynthetases with antisynthetase syndrome, anti-SRP with severe, resistant to treatment myositis, anti-Mi-2 with classic, benign dermatomyositis. Therefore it is important to include the myositis specific antibodies into routine diagnostic scheme of IIM.     

Caspase inhibitors reduce neuronal injury after focal but not global cerebral ischemia in rats

BACKGROUND AND PURPOSE: Studies show that blocking the activation of caspases by the caspase inhibitors z-VAD.FMK and z-DEVD.FMK can reduce ischemic neuronal injury after cerebral ischemia. Because the severity of ischemia was mild in some studies, we tested the efficacy of these caspase inhibitors on moderately severe but transient forebrain and focal ischemic insults in the rat. METHODS: Various regimens of z-VAD, z-DEVD, and control DMSO were given to rats subjected to either 4-vessel occlusion ischemia (4-VO, 10-minute occlusion, 7-day survival) or distal middle cerebral artery occlusion (MCAo, 90-minute occlusion, 22.5-hour survival). In global ischemia, treatments were given immediately after ischemia (experiment 1) or as preischemic and postischemic treatments (experiment 2). Three focal ischemia experiments were done. Injection times were 60 minutes into ischemia (experiment 1) and 60 minutes into ischemia plus 30 and 120 minutes after ischemia (experiment 2). Experiment 3 was identical to experiment 2 except that a 30-minute preischemia treatment was instituted. Core normothermia was maintained in all experiments during ischemia. However, in the last focal and global experiments, core and brain temperatures, respectively, were also measured after ischemia with telemetry probes. Because hyperthermia accompanied z-DEVD treatment, an extra z-DEVD-treated group (MCAo) was included with temperature clamped at normothermia. RESULTS: Neither z-VAD nor z-DEVD significantly reduced CA1 injury after global ischemia. In focal ischemia, both drugs significantly reduced infarction, but only in the third experiment, and the prevention of hyperthermia that accompanied z-DEVD treatment did not alter this. CONCLUSIONS: These results suggest a detrimental role of caspases in moderately severe focal but not global cerebral ischemia.     

Dendritic L-type calcium currents in mouse spinal motoneurons: implications for bistability

The intrinsic properties of mammalian spinal motoneurons provide them with the capability to produce high rates of sustained firing in response to transient inputs (bistability). Even though it has been suggested that a persistent dendritic calcium current is responsible for the depolarizing drive underlying this firing property, such a current has not been demonstrated in these cells. In this study, calcium currents are recorded from functionally mature mouse spinal motoneurons using somatic whole-cell patch-clamp techniques. Under these conditions a component of the current demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late-onset, low amplitude persistent current whilst in response to depolarizing-repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments. Pharmacological studies demonstrated that both the late-onset and hysteretic currents demonstrated sensitivity to both dihydropyridines and the L-channel activator FPL-64176. Furthermore, the alpha1D subunits of L-type calcium channels were immunohistochemically demonstrated on motoneuronal dendrites. It is concluded that there are dendritically located L-type channels in mammalian motoneurons capable of mediating a persistent depolarizing drive to the soma and which probably mediate the bistable behaviour of these cells.     

Characterization of calcium currents in functionally mature mouse spinal motoneurons

Motoneurons integrate synaptic input and produce output in the form of trains of action potentials such that appropriate muscle contraction occurs. Motoneuronal calcium currents play an important role in the production of this repetitive firing. Because these currents change in the postnatal period, it is necessary to study them in animals in which the motor system is 'functionally mature', that is, animals that are able to weight-bear and walk. In this study, calcium currents were recorded using whole-cell patch-clamp techniques from large (> 20 microm) ventral horn cells in lumbar spinal cord slices prepared from mature mice. Ninety percent (nine out of 10) of the recorded cells processed for choline acetyltransferase were found to be cholinergic, confirming their identity as motoneurons. A small number of motoneurons were found to have currents with low-voltage-activated (T-type) characteristics. Pharmacological dissection of the high-voltage-activated current demonstrated omega-agatoxin-TK- (P/Q-type), omega-conotoxin GVIA- (N-type), and dihydropyridine- and FPL-64176-sensitive (L-type) components. A cadmium-sensitive component of the current that was insensitive to these chemicals (R-type) was also seen in these cells. These results indicate that the calcium current in lumbar spinal motoneurons from functionally mature mice is mediated by a number of different channel subtypes. The characterization of these calcium channels in mature mammalian motoneurons will allow for the future study of their modulation and their roles during behaviours such as locomotion.     

Genetic analysis of learning behavior-induced structural plasticity

It is well-documented that enriched environment and behavioral training can lead to improved learning and memory, as well as structural and morphological changes in the brain. It has been hypothesized that such experience-dependent behavioral improvement results from structural modifications that may represent some forms of possible memory substrates for these behavioral experiences. It was generally assumed until now that, like the activity-dependent structural plasticity observed in the developing brain, behavioral experience-induced structural plasticity would require the activation of the NMDA receptor, a molecular switch for learning and memory. Recent genetic and anatomical analyses reveal that behavioral experience-induced increases in spine and synapse density in the hippocampal CA1 region occur despite the deletion of the NMDA receptor in conditional knockout mice. Recent studies indicate that the molecular mechanism of behavioral experience-induced structural plasticity in the adult brain differs from that of the developing brain, and can be disassociated from the NMDA-mediated long-term potentiation (LTP) phenomenon. Deepening the understanding of the molecular mechanism of experience-induced structural plasticity should facilitate the study of the relationship between structural changes and memory formation. Using an integrated approach with genomic, genetic, and modern histological techniques should move us closer in this direction.     

Analysis of spine morphological plasticity in developing hippocampal pyramidal neurons

Dendritic spines are targets of most excitatory inputs in the central nervous system (CNS) and are morphologically heterogeneous. Ultrastructural studies have traditionally classified spines into four major categories (filopodia, stubby, thin, and mushroom) based on their distinct morphologies. The recent discovery of rapid morphological plasticity of spines has raised the possibility that those categories, rather than being intrinsically different populations of spines, represent instead temporal snapshots of a single dynamic phenomenon. We examined this question with two-photon time-lapse imaging of developing hippocampal pyramidal neurons, transfected with E-GFP in cultured slices. After blind scoring to morphologically classify spines into the four traditional groups, we analyzed the fate of populations of spines over a period of 2-4 h. We found considerable morphological conversions among all categories, although systematic trends were detected. While most stubbies and spines (defined for our analysis as the combination of thin and mushroom protrusions) retained their basic morphologies, most filopodia transformed into stubbies and spines, although they could also extend out of existing spines. Our results suggest that in developing hippocampal pyramidal neurons, traditional morphological distinctions are stable over short (<4 h) periods of time, but that at the same time, considerable mixing among these groups takes place.     

Health consequences of obesity.

The recent epidemic of childhood obesity(1) has raised concern because of the possible clinical and public health consequences.(2,)(3) However, there remains a widespread perception among health professionals that childhood obesity is a largely cosmetic problem, with minor clinical effects. No systematic review has yet focused on the diverse array of possible consequences of childhood obesity, though older non-systematic reviews are available.(4,)(5) In addition, no review to date has considered the vast body of evidence on the health impact of childhood obesity which has been published recently. The aim of the present review was therefore to provide a critically appraised, evidence based, summary of the consequences of childhood obesity in the short term (for the child) and longer term (in adulthood).     

Electrogustometry: strengths,weaknesses, and clinical evidence of stimulus boundaries

Electrogustometry is well established as a clinical tool for the estimation of taste detection thresholds. Nevertheless, the user is sometimes unaware of the impact of superficially minor procedural and psychophysical factors upon the reliability and comparability of threshold estimates. The inherent strengths and limitations of the procedure are outlined, and aspects of the control and specification of the stimulus that moderate threshold measures are discussed. In addition, threshold estimates from two individuals with severe unilateral taste loss are used to illustrate the level at which anodal dc current may elicit common, rather than taste, sensation. Where chorda tympani section is complete and historical (older than 7–14 days), very high stimulus levels, conservatively over 5 µA/mm² (100 µA linear current with a 5‐mm diameter electrode), are required to activate trigeminal responses.