Immune function and HPA axis activity in free-ranging rhesus macaques

In mammals, the hypothalamic-pituitary-adrenal (HPA) axis and immune system play an important role in the maintenance of homeostasis. Dysregulation of either system resulting, for example, from psychosocial or reproductive stress increases susceptibility to disease and mortality risk, especially in aging individuals. In a study of free-ranging rhesus macaques, we examined how female age, reproductive state, social rank, and body condition influence (i) aspects of cytokine biology (plasma concentrations of interleukin-1 receptor antagonist (IL-1ra), IL-6 and IL-8), and (ii) HPA axis activity (plasma and fecal glucocorticoid levels). We also assessed individual differences in cytokine and hormone concentrations over time to determine their consistency and to investigate relations between these two indicators of physiological regulation and demand. Female monkeys showed marked increases in HPA axis activity during pregnancy and lactation, and increased circulating levels of IL-1ra with advancing age. Inter-individual differences in IL-1ra and IL-8 were consistent over successive years, suggesting that both are stable, trait-like characteristics. Furthermore, the concentrations of fecal glucocorticoid hormones in non-pregnant, non-lactating females were correlated with their plasma cortisol and IL-8 concentrations. Some individuals showed permanently elevated cytokine levels or HPA axis activity, or a combination of the two, suggesting chronic stress or disease. Our results enhance our understanding of within- and between-individual variation in cytokine levels and their relationship with glucocorticoid hormones in free-ranging primates. These findings can provide the basis for future research on stress and allostatic load in primates.     

Estimation of Grasping Force from Features of Intramuscular EMG Signals with Mirrored Bilateral Training

This study investigates the use of features extracted from intramuscular electromyography (EMG) for estimating grasping force in the ipsilateral and contralateral (mirrored) hand, during bilateral grasping tasks. This is relevant since force estimation using mirror tasks is a potentially useful pathway for the clinical training of unilateral amputees. Bilateral grasping force and intramuscular EMG (wire electrodes) of the right forearm were measured in 10 able-bodied subjects. The features extracted from the EMG signal were the root mean square, the global discharge rate, the standard sample entropy, and the constraint sample entropy (CSE). The association between the EMG features and force was modeled using a first-order polynomial model, a second-order exponential model, and an artificial neural network (ANN). The accuracies of estimation of ipsilateral and mirrored grasping force were not significantly different (e.g., R ² = 0.89 ± 0.02 for ipsilateral and 0.88 ± 0.017 for mirrored, when using CSE and the ANN). It was concluded that it is possible to use just one channel of intramuscular EMG for force estimation. This result suggests that intramuscular EMG signals may be suitable for proportional myoelectric control and that training of the association between intramuscular EMG features and force can be performed using mirror tasks, which is a needed condition for applications in unilateral amputees.     

State-of-the-art on basic and applied stem cell therapy; Stem Cell Research Italy-International Society for Cellular Therapy Europe, Joint Meeting, Montesilvano (PE)-Italy, June 10-12, 2011

Over 160 stem cell-based therapeutic products are undergoing development for the treatment of several diseases, ranging from cardiac and artery diseases to immune and neurodegenerative pathologies, including diabetes, spinal cord injury. Therefore, stem cell therapy plays a key role for developing new cell-based drugs for the future molecular and regenerative medicine. The second meeting organized by Stem Cell Research Italy (SCR Italy) and by the International Society for Cellular Therapy-Europe (ISCT) in Montesilvano/Città S. Angelo (Pescara)-Italy, on June 10th-12th, 2011, focused on the state-of-the-art of stem cell therapy and associated novel findings on stem cell research ( www.stemcellitaly.org ).     

Upper trapezius muscle mechanomyographic and electromyographic activity in humans during low force fatiguing and non-fatiguing contractions

The purposes of this study were firstly to compare and investigate localised fatigue in the upper trapezius muscle in various arm positions as assessed by mechanomyographic (MMG) and surface electromyographic (EMG) signals and secondly to study the effects of different normalisation methods on MMG and EMG signals during non-fatiguing and fatiguing low level isometric contractions. The MMG, EMG and rate of perceived exertion were recorded from 11 subjects in five arm positions (0° abduction and 0° flexion, 45° and 90° flexion, 45° and 90° abduction) with different bilateral arm loads during 3 s for non-fatiguing (0–0.5–1 kg hand-load) and 3 min for fatiguing contractions (1 kg hand-load). The root mean square (RMS), average rectified value (ARV), mean power frequency (MNF), and median power frequency (MDF) of the MMG and EMG signals were computed and normalised with respect to the initial values obtained in the current arm position or in the reference position (0° abduction and 0° flexion) corresponding to the normal postural activity of the trapezius muscle. For fatiguing contractions, differences in magnitude of the increase in the RMS or ARV and decrease in the MNF or MDF were observed for EMG and MMG. The MMG amplitude and spectral changes followed the subjective sensation of fatigue and were not correlated to their EMG counterparts, suggesting that they may reflect different phenomena. For non-fatiguing contractions, normalisation to the current arm position entailed the loss of dynamic amplitude changes suggesting that a single reference contraction in the middle part of the range of movement is enough for proper normalisation of EMG and MMG signals. For fatiguing contractions, normalisation of the EMG and MMG to some extent can lead to a misleading interpretation. Assessment of the upper trapezius muscle by means of MMG may be valuable in ergonomics. Electronic Publication     

High prevalence of the G101W germline mutation in the CDKN2A (P16ink4a) gene in 62 Italian malignant melanoma families

CDKN2A germline mutation frequency estimates are commonly based on families with several melanoma cases. When we started counseling in a research setting on gene susceptibility analysis in northern and central Italy, however, we mostly found small families with few cases. Here we briefly characterize those kindred, estimate CDKN2A/CDK4 mutation test yields, and provide indications on the possibility of implementing formal DNA testing for melanoma‐prone families in Italy. In September 1995 we started genetic counseling in a research setting at our Medical Genetics Center. Screening for CDKN2A/CDK4 mutations was performed on families with two melanoma patients, one of whom was younger than 50 years at onset, the other complying with one of the following: 1) being a first‐degree relative, 2) having an additional relative with pancreatic cancer, or 3) having multiple primary melanomas. Sixty‐two of 67 (80%) melanoma cases met our criteria. Four previously described CDKN2A mutations (G101W, R24P, V126D, and N71S) were found in 21 of the 62 families (34%) with a high prevalence of G101W (18/21). The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. In the 15 families with three melanoma cases the presence of a mutation was higher (67%, 10/15) and reached 100% in the 4 families with four or more melanoma cases. Our results suggest that CDKN2A/CDK4 counseling‐based mutational analysis may be reasonably efficient also for families with two melanoma cases, if one patient carries multiple melanomas or if pancreatic cancer is present in the family. © 2002 Wiley‐Liss, Inc.     

Conduction velocity of quiescent muscle fibers decreases during sustained contraction

We tested the hypothesis that conduction velocity of quiescent muscle fibers decreases during sustained contraction due to the activity of the active motor units in the muscle. Ten subjects trained for the identification of a target motor unit in the abductor pollicis brevis with feedback on surface EMG signals detected with a two-dimensional array of 61 electrodes. The subjects activated the target motor unit in two 10-s long contractions, before (contraction C1) and after (C3) a 3-min contraction (C2), all in ischemic condition. The target motor unit was not activated during C2. Eight of the 10 subjects (control group) performed a second experimental session identical to the first but with a resting period of 3 min instead of the contraction C2. Exerted force and target motor unit discharge rate were not different between the two subject groups and between C1 and C3 (mean +/- SD, over C1 and C3; C2 group: 15.8 +/- 10.4% maximal voluntary contractions and 13.1 +/- 1.9 pps; control group: 15.6 +/- 22.1% maximal voluntary contractions and 14.5 +/- 1.9 pps, respectively). Muscle fiber conduction velocity of the target motor unit decreased in C3 with respect to C1 in the C2 group (3.59 +/- 0.57 and 3.34 +/- 0.47 m/s for C1 and C3, respectively; P < 0.05) but not in the control group (3.47 +/- 0.68 and 3.46 +/- 0.73 m/s). In the C2 group, the percent decrease in conduction velocity of the target motor unit between C1 and C3 (6.4 +/- 7.1%) was not significantly different from the percent decrease in the average conduction velocity of the motor units active during C2 (9.6 +/- 5.4%). In conclusion, the contraction-induced modifications in electrophysiological membrane properties of muscle fibers are partly independent on fiber activation.     

Light signaling in scotopic conditions in the rabbit, mouse and rat retina: a physiological and anatomical study

In the dark, light signals are conventionally routed through the following circuit: rods synapse onto rod bipolar (RB) cells, which in turn contact AII amacrine cells. AII cells segregate the light signal into the on and off pathways by making electrical synapses with on cone bipolar (CB) cells and glycinergic inhibitory chemical synapses with off CB cells. These bipolar cells synapse onto their respective ganglion cells, which transfer on and off signals to the visual centers of the brain. Two alternative pathways have recently been postulated for the signal transfer in scotopic conditions: 1) electrical coupling between rods and cones, and 2) a circuit independent of cone photoreceptors, implying direct contacts between rods and off CB cells. Anatomical evidence supports the existence of both these circuits. To investigate the contribution of these alternative pathways to scotopic vision in the mammalian retina, we have performed patch-clamp recordings from ganglion cells in the dark-adapted retina of the rabbit, mouse, and rat. Approximately one-half of the ganglion cells in the rabbit retina received off signals through a circuit that was independent of RB cells. This was shown by their persistence in the presence of the glutamate agonist 2-amino-4-phosphonobutyric acid (APB), which blocks rod-->RB cell signaling. Consistent with this result, strychnine, a glycine receptor antagonist, was unable to abolish these off responses. In addition, we were able to show that some off cone bipolar dendrites terminate at rod spherules and make potential contacts. In the mouse retina, however, there seems to be a very low proportion of off signals carried by an APB-resistant pathway. No ganglion cells in the rat retina displayed APB- and strychnine-resistant responses. Our data support signaling through flat contacts between rods and off CB cells as the alternative route, but suggest that the significance of this pathway differs between species.