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At least 145 records · Page 8Linked to original sources

PubMed2005

Automatic determination of synergies by radial basis function artificial neural networks for the control of a neural prosthesis.

This paper describes an automatic method for synthesizing the control for a neural prosthesis (NP) that could augment elbow flexion/extension and forearm pronation/supination in persons with hemiplegia. The basis for the control was a synergistic model of reaching and grasping that uses temporal and spatial synergies between the arm and body segments. The synergies were determined from the movement data measured in nondisabled persons during the performance of functional tasks. The work space was divided into six zones: distance (two attributes) and laterality (three attributes). Radial basis function artificial neural networks (RBF ANN) were used to determine synergies. Sets of RBF ANN characterized with good generalization were selected as control laws for elbow flexion/extension and forearm pronation/supination. The validation was performed for three categories: inter-subject, distance, and laterality generalization. For all of the defined spatial synergies, the correlation was high for inter-subject and distance, yet low for the laterality scenario. This suggests the necessity for implementing different maps for different directions, but the same maps for different distances. The natural movements of the upper arm then drive the lower arm (elbow flexion/extension and forearm pronation/supination) in a way that is very well suited for the administration of functional electrical therapy (FET) in persons with hemiplegia soon after the onset of impairment.

Activities of Daily Living↗

PubMed2005

Muscle synergies at the elbow in static and oscillating isometric torque tasks with dual degrees of freedom.

This study's aim was to identify the effect of oscillation of torques in isometric tasks under identical mechanical conditions on the muscle synergies used. It was hypothesized that bi-functional muscles would play a lesser role in torque oscillation, because they would also generate an undesired oscillation. Thus, changes in muscle synergies were expected as a consequence of oscillation in torque generation. The effect of the trajectory of torque generation was investigated in dual-degrees-of-freedom submaximal isometric oscillation torque tasks at the elbow. The torques were flexion-extension and supination-pronation. Oscillation torques were compared with static torque generations at four torque positions during oscillation. Muscle activity was determined with surface electromyography. Compared with the static torque tasks, the oscillation tasks showed an overall increased muscle activity. The oscillation tasks, however, showed similar activity patterns and muscle synergies compared to the static composite tasks. It was found that the motor system is well able to control different orthogonal combinations of slow torque oscillations and constant torques by employing a single oscillating muscle synergy.

Adolescent↗

PubMed2002

Synergy between mu opioid ligands: evidence for functional interactions among mu opioid receptor subtypes.

Pharmacological differences among mu opioid drugs have been observed in in vitro and in vivo preclinical models, as well as clinically, implying that all mu opioids may not be working through the same mechanism of action. Here we demonstrate analgesic synergy between L-methadone and several mu opioid ligands. Of the compounds examined, L-methadone selectively synergizes with morphine, morphine-6beta-glucuronide, codeine, and the active metabolite of heroin, 6-acetylmorphine. Morphine synergizes only with L-methadone. In analgesic assays, D-methadone was inactive alone and did not enhance morphine analgesia when the two were given together, confirming that L-methadone was not acting through N-methyl-D-aspartate mechanisms. Both L-methadone and morphine displayed only additive effects when paired with oxymorphone, oxycodone, fentanyl, alfentanyl, or meperidine. Although it displays synergy in analgesic assays, the L-methadone/morphine combination does not exhibit synergy in the gastrointestinal transit assay. This analgesic synergy of L-methadone with selective mu opioid drugs and the differences in opioid-mediated actions suggest that these drugs may be acting via different mechanisms. These findings provide further evidence for the complexity of the pharmacology of mu opioids.

Analgesics, Opioid↗

PubMed1982

Synergy of fosmidomycin (FR-31564) and other antimicrobial agents.

Fosmidomycin (FR-31564), a phosphonic acid derivative, was combined with cefazolin, cephalexin, ampicillin, carbenicillin, ticarcillin, gentamicin, and trimethoprim. Synergy between fosmidomycin and penicillins or cephalosporins was found for 37 to 52% of the Enterobacteriaceae tested. Synergy with trimethoprim was found against 55% of bacteria isolated, but only 17% of the strains showed synergy between formidomycin and gentamicin. Synergy between fosmidomycin and ticarcillin was shown for 35% of the Pseudomonas isolates. Cefazolin-, ampicillin-, and gentamicin-resistant isolates of various species were synergistically inhibited by fosmidomycin, as were ticarcillin- and gentamicin-resistant isolates. Antagonism was not encountered. This study illustrates another example of synergistic activity of compounds which attack different mechanisms in bacterial cells.

Anti-Bacterial Agents↗

PubMed2003

In vitro synergy of caspofungin and itraconazole against Aspergillus spp.: MIC versus minimal effective concentration end points.

Caspofungin and itraconazole were studied alone and in combination against 31 clinical isolates of Aspergillus spp. according to NCCLS M38-P guidelines. MICs and microscopic minimal effective concentrations (MECs) were recorded, and synergy was calculated by using both end points. Synergy or synergy to additivity was found in 30 of 31 isolates by using MIC end points. With MEC end points no synergy was found and indifference was detected in 26 of 31 strains.

Anti-Bacterial Agents↗

PubMed1976

In vivo synergy between 6 beta-amidinopenicillanic acid derivatives and other antibiotics.

Both an oral and a parenteral form of a 6beta-amidinopenicillanic acid derivative were found to have appreciable activity against gram-negative bacteria and poor activity against gram-positive bacteria in vivo. When administered orally or parenterally, definite synergy was demonstrated between the amidinopenicillins and ampicillin, amoxicillin, benzylpenicillin, cefazolin, or carbenicillin in infections with a number of gram-negative bacteria, including Klebsiella, Enterobacter, Escherichia, Proteus, Salmonella, and Haemophilus species in mice. Synergy was also observed between the parenteral amidinopenicillin and benzylpenicillin in the Staphylococcus aureus infection but not in infections with other gram-positive organisms. No synergy was demonstrated between the parenteral amidinopenicillin and erythromycin or oxytetracycline in infections with gram-positive or gram-negative organisms. Synergy between the parenteral amidinopenicillin and gentamicin was observed only in the case of Escherichia coli.

Animals↗

PubMed2005

Synergy in polymicrobial infections in a mouse model of type 2 diabetes.

Human diabetics frequently suffer delayed wound healing, increased susceptibility to localized and systemic infections, and limb amputations as a consequence of the disease. Lower-limb infections in diabetic patients are most often polymicrobial, involving mixtures of aerobic, facultative anaerobic, and anaerobic bacteria. The purpose of this study is to determine if these organisms contribute to synergy in polymicrobial infections by using diabetic mice as an in vivo model. The model was the obese diabetic mouse strain BKS.Cg-m +/+ Lepr(db)/J, a model of human type 2 diabetes. Young (5- to 6-week-old) prediabetic mice and aged (23- to 24-week-old) diabetic mice were compared. The mice were injected subcutaneously with mixed cultures containing Escherichia coli, Bacteroides fragilis, and Clostridium perfringens. Progression of the infection (usually abscess formation) was monitored by examining mice for bacterial populations and numbers of white blood cells at 1, 8, and 22 days postinfection. Synergy in the mixed infections was defined as a statistically significant increase in the number of bacteria at the site of injection when coinfected with a second bacterium, compared to when the bacterium was inoculated alone. E. coli provided strong synergy to B. fragilis but not to C. perfringens. C. perfringens and B. fragilis provided moderate synergy to each other but only in young mice. B. fragilis was anergistic (antagonistic) to E. coli in coinfections in young mice at 22 days postinfection. When age-matched nondiabetic mice (C57BLKS/J) were used as controls, the diabetic mice exhibited 5 to 35 times the number of CFU as did the nondiabetic mice, indicating that diabetes was a significant factor in the severity of the polymicrobial infections.

Abscess↗

PubMed2000

A common motif within the negative regulatory regions of multiple factors inhibits their transcriptional synergy.

DNA regulatory elements frequently harbor multiple recognition sites for several transcriptional activators. The response mounted from such compound response elements is often more pronounced than the simple sum of effects observed at single binding sites. The determinants of such transcriptional synergy and its control, however, are poorly understood. Through a genetic approach, we have uncovered a novel protein motif that limits the transcriptional synergy of multiple DNA-binding regulators. Disruption of these conserved synergy control motifs (SC motifs) selectively increases activity at compound, but not single, response elements. Although isolated SC motifs do not regulate transcription when tethered to DNA, their transfer to an activator lacking them is sufficient to impose limits on synergy. Mechanistic analysis of the two SC motifs found in the glucocorticoid receptor N-terminal region reveals that they function irrespective of the arrangement of the receptor binding sites or their distance from the transcription start site. Proper function, however, requires the receptor's ligand-binding domain and an engaged dimer interface. Notably, the motifs are not functional in yeast and do not alter the effect of p160 coactivators, suggesting that they require other nonconserved components to operate. Many activators across multiple classes harbor seemingly unrelated negative regulatory regions. The presence of SC motifs within them, however, suggests a common function and identifies SC motifs as critical elements of a general mechanism to modulate higher-order interactions among transcriptional regulators.

Amino Acid Sequence↗

PubMed2006

Sequential activation of muscle synergies during locomotion in the intact cat as revealed by cluster analysis and direct decomposition.

During goal-directed locomotion, descending signals from supraspinal structures act through spinal interneuron pathways to effect modifications of muscle activity that are appropriate to the task requirements. Recent studies using decomposition methods suggest that this control might be facilitated by activating synergies organized at the level of the spinal cord. However, it is difficult to directly relate these mathematically defined synergies to the patterns of electromyographic activity observed in the original recordings. To address this issue, we have used a novel cluster analysis to make a detailed study of the organization of the synergistic patterns of muscle activity observed in the fore- and hindlimb during treadmill locomotion. The results show that the activity of a large number of forelimb muscles (26 bursts of activity from 18 muscles) can be grouped into 11 clusters on the basis of synchronous co-activation. Nine (9/11) of these clusters defined muscle activity during the swing phase of locomotion; these clusters were distributed in a sequential manner and were related to discrete behavioral events. A comparison with the synergies identified by linear decomposition methods showed some striking similarities between the synergies identified by the different methods. In the hindlimb, a simpler organization was observed, and a sequential activation of muscles similar to that observed in the forelimb during swing was less clear. We suggest that this organization of synergistic muscles provides a means by which descending signals could provide the detailed control of different muscle groups that is necessary for the flexible control of multi-articular movements.

Animals↗

PubMed1985

Intralimb coordination of the paw-shake response: a novel mixed synergy.

Intralimb coordination of the paw-shake response (PSR) was studied in five normal and eleven spinal adult cats. Representative extensor and flexor muscles that function at the hip, knee, and ankle joints were recorded, and in six spinal cats the kinematics of these joints were determined from high-speed cinefilm. The PSR was characterized uniquely by mixed (flexor-extensor) synergies. Knee extensor (VL) and ankle flexor (TA) coactivity constituted one synergy, while the second synergy included hip extensors (GM, BF), knee flexors (BF, LG), and ankle extensor (LG). Joint displacements reflected the mixed synergy. Motions at the knee and ankle were out of phase, while motions at the hip were in phase with movements of the knee. Electromyographic burst durations and onset latencies were similar for normal and spinal cats, and in all cycles of a given PSR, the recruitment pattern was consistent for all muscles, except VL. High variability and missing bursts marked the activity of VL in some spinal cats. In PSRs with missing VL bursts, oscillations at the knee joint were not coordinated with cyclic actions at the hip and ankle. From the kinematic records three distinct phases of the PSR were identified: start-up consisted of the initial four to six cycles during which hip, knee, and ankle actions progressively became organized; steady-state included the middle three to five cycles that were characterized by consistent displacement at all three joints; and slow-down comprised the last three to four cycles during which the rate of oscillations slowed, and joint excursions decreased. During steady-state cycles, muscle contractions acted to reverse joint motions at the knee and ankle joints. Thus, knee and ankle extensor recruitment coincided with joint flexion, while joint flexors were recruited during joint extension. Muscle activity at the hip, however, was in phase with displacement. While neural input to muscle is consistent throughout the three phases of the PSR, segment motions can become progressively organized during start-up to achieve stable oscillations. Whether the PSR attains steady-state or not may hinge on the sensitive interplay that occurs between muscle activities and intersegmental mechanical interactions. That kinetic interplay is detailed in the following paper.

Animals↗

PubMed1978

Synergy studies with Pseudomonas aeruginosa resistant to gentamicin and/or carbenicillin.

The predictability of synergy with strains of Pseudomonas aeruginosa highly resistant to gentamicin in combination with carbenicillin has been controversial. 30 clinical isolates of P. aeruginosa resistant to gentamicin and/or carbenicillin were tested by checker-board technique. 14 were found to be highly resistant to gentamicin (minimal inhibitory concentration MIC greater than or equal to 128 microgram/ml) and/or carbenicillin (MIC greater than or equal to 512 microgram/ml). Of these 14, 4 isolates showed synergy. 10 of 16 isolates with moderate resistance demonstrated synergy. It is concluded that the level of resistance to gentamicin with P. aeruginosa cannot be used in predicting whether synergy will occur.

Carbenicillin↗

PubMed1991

Overview of synergy with reference to double beta-lactam combinations.

Combination antimicrobial therapy is used to expand the bacterial coverage over a single agent, to prevent the emergence of resistant organisms, to decrease toxicity by allowing lower doses of both agents, or for synergy. Synergy is one of the most common of these reasons, especially in serious infections. The introduction of new broad-spectrum beta-lactam antimicrobials has led to their combination in the treatment of seriously ill patients. Whereas a combination of an aminoglycoside and a beta-lactam antimicrobial is frequently synergistic, much less is known about synergy between combinations of beta-lactams. In vitro testing shows most combinations of two beta-lactams to be indifferent or additive in their effects; rarely does synergy occur. Antagonism can sometimes be seen, particularly with combinations involving cefoxitin or imipenem, especially if the treated organism is Enterobacter or Pseudomonas. Results of clinical trials comparing double beta-lactam (DBL) therapy with aminoglycoside/beta-lactam combinations show no difference in clinical response rates. Highly active DBL combinations may substitute for standard aminoglycoside-containing regimens in certain situations, even though they are not reliably synergistic. However, in the treatment of seriously ill patients such combinations may be less desirable.

Anti-Bacterial Agents↗

PubMed1999

Postural synergies associated with a stepping task.

BACKGROUND AND PURPOSE: Synergistic relationships among multiple muscle components are thought to exist to simplify control of posture and movement. The purpose of this study was to examine the extent to which children, young adults, and older adults exhibit consistent sequences of postural muscle activation when lifting the right foot onto a step from a standing position. SUBJECTS: Twenty subjects without known impairments of the neuromuscular system (10 male, 10 female) in each of 3 age groups--children (8-12 years), young adults (25-35 years), and older adults (65-73 years)--participated. METHODS: A pressure switch taped to the subject's right foot was used to determine movement onset and offset. Latencies of muscle activation were determined using surface electromyography. A preferred postural synergy was defined as the sequence of postural muscle activation observed during the majority of trials for each subject. RESULTS: Mean movement times did not differ among age groups. Although the left tibialis anterior (TA) muscle was the first of the postural muscles activated in 93% of the trials, subjects displayed considerable variability in the subsequent order of postural muscle activation. Across subjects, a total of 14 different preferred postural synergies were observed. Age groups did not differ in the number of different synergies. CONCLUSION AND DISCUSSION: Early TA activation may reflect biomechanical constraints of the stepping task, producing forward displacement of the center of mass over the changing base of support. The fact that subjects of all ages were quite variable in the specific sequences of muscles activated subsequent to the TA suggests that, for this type of task, therapists should not focus their interventions on facilitating execution of particular synergy patterns.

Adolescent↗

PubMed2003

Thymidine and hypoxanthine protection patterns of the folic acid-enhanced synergies for combinations of trimetrexate plus a polyglutamylatable inhibitor of purine or thymidylate synthesis against human ileocecal HCT-8 cells.

In order to examine the intracellular locus of the folic acid (PteGlu)-enhanced synergies of trimetrexate (TMQ) plus the thymidylate synthase (TS) inhibitor, raltitrexed (RTX), and TMQ plus the glycinamide ribonucleotide formyltransferase (GARFT) inhibitor, AG2034, comprehensive protection studies with thymidine (dThd) and hypoxanthine (HX) were conducted in a 96-well plate cell growth inhibition (sulforhodamine B) assay. Current modeling techniques were extended to characterize these protection patterns involving multiple-agent interaction. Wild-type human ileocecal HCT-8 cells and DW2, a subline deficient in folylpoly-gamma-glutamate synthetase (FPGS) were individually treated for 96 h with TMQ, AG2034 and a 1:1 mixture of TMQ:AG2034 or with TMQ, RTX, and a 1:1 mixture of TMQ:RTX in the presence of PteGlu (2.3 or 40 micro M) and the protection agents (10 micro M dThd and/or 100 micro M HX). Drug treatments were randomly assigned to wells. Both isobols and 3-dimensional concentration-effect surfaces were used to assess the nature and the intensity of drug interactions. The structural Hill model was fitted to data with weighted non-linear regression for most cases. A so-called 'double Hill' model was sometimes more appropriate when a plateau in the middle of the concentration-effect curve was found. In HCT-8 and DW2 cells at 2.3 and 40 micro M PteGlu, inhibition of DHFR by TMQ induced antithymidylate and antipurine effects; AG2034 and RTX selectively inhibited de novo purine or thymidine synthesis, respectively. dThd protection increased the PteGlu-enhancement of the TMQ + AG2034 synergy, whereas HX protection increased the PteGlu-enhancement of the TMQ + RTX synergy. The PteGlu-enhanced synergies of TMQ + AG2034 and TMQ + RTX occur primarily through inhibition of purine synthesis and inhibition of thymidylate synthesis, respectively. These results further substantiate the hypothesis that the nonpolyglutamylatable DHFR inhibitor, TMQ, acts as a modulator by decreasing the protection by PteGlu of cells against the polyglutamylatable AG2034 and RTX.

Adenocarcinoma↗

PubMed1980

[Gestalt synergy.].

The author describes a new psychotherapeutic approach called Gestalt Synergy. After presenting it's originality among others Body/Mind approaches, the author retraces the history of it's development through the personal history of the founder of Gestalt Synergy : Ilana Rubenfeld. Then follows an introduction of the Alexander Technique and the Feldenkrais Method which, with Gestalt, inspired Gestalt Synergy. The concepts and techniques of Gestalt Synergy are discussed and, the sequence of one session is illustrated. The author concludes on some personal changes noted from her use of this approach.

English Abstract↗

PubMed1991

Determination of the synergy of antibiotic combinations by an overlay inoculum susceptibility disc method.

A method involving an overlay inoculum agar and antibiotic susceptibility discs in the determination of synergy of gentamicin and disc antibiotics against clinical isolates of Pseudomonas aeruginosa has been described. Gentamicin combinations with carbenicillin showed synergism against all test isolates. Combinations containing fosfomycin had indifferent effects. Netilmicin, ceftriaxone and ampicillin, respectively, produced interisolate variations in the synergy of their combinations with gentamicin. In all cases synergy was determined on the basis of correlations between inhibition zone diameter (IZD) increments and fractional inhibitory concentration (FIC) indices. An IZD increment of 19% or more predominantly corresponded with synergy. Cases showing less than 19% increase in IZD produced additive effects, while cases showing no variations in IZD had indifferent effects.

Anti-Bacterial Agents↗

PubMed1979

Synergy between T cell-replacing factor and bacterial lipopolysaccharides (LPS) in the primary antibody response in vitro: a model for lipopolysaccharide adjuvant action.

Unfractionated spleen cells, B cells from normal mice, and nu/nu spleen cells respond to the addition of bacterial lipopolysaccharide (LPS) and T-cell-replacing factor (TRF) by production of plaque-forming cells (PFC) in excess of the number expected from the addition of LPS and TRF separately. This synergistic activity is dependent on the presence of the antigen, SRBC. Supernatants of both allogeneic spleen cell mixtures and spleen cells cultured with Con A are effective and synergize best at concentrations suboptimal for their ability to act as TRF alone. Culture supernatants of unstimulated normal or fractionated cell populations are ineffective. Synergy is not dependent on the presence of macrophages in the cultures. Purified LPS free from active contaminants, as well as commercially available LPS, show synergy with TRF. Synergy was seen when TRF was added at initiation of culture or 24 hr later. It is suggested that synergy is the equivalent of LPS adjuvant activity, that the role of T cells in LPS adjuvanticity is that of a conventional cooperating cell, and the LPS acts as an adjuvant by inducing B cells to become more sensitive to T cell helper factors.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Rapid determination of the synergy of clavulanic acid and beta lactams by measuring the intracellular ATP by bioluminescence].

Twenty clinical isolates of ampicillin- and carbenicillin-resistant or susceptible (two strains) Gram-negative rods, producing at least one beta-lactamase, were examined for susceptibility to a combination of ampicillin or carbenicillin with clavulanic acid (enzymatic inhibitor). Synergy was evaluated by the reduction of the beta-lactam agar dilution MIC and by the measurement of intracellular AYP using firefly bioluminescence. The potentiation effect of clavulanic acid was variable, depending on resistance levels, species and types of beta-lactamase (TEM, SHV-1, CARB, OXA, MAL and Cpase). The synergy was significant, with 10 mg/l of inhibitor for all the strains producing TEM-1, TEM-2 and Carb-2 except for one strain of Serratia marcescens (TEM-2). The synergy was weak for Levinea strains (Citrobacter diversus biotype b), biosynthesizing specific penicillinases as MAL-1. No potentiation effect was observed for strains producing a cephalosporinase, such as Escherichia coli and Pseudomonas aeruginosa. This effect appeared to be variable for strains producing the oxacillin-hydrolysing enzyme (OXA-1), such as E. coli and P. aeruginosa. A positive correlation was clearly demonstrated between the MIC values and the intracellular ATP concentration in bacteria within 2 h. The opportunity of using the firefly assay for the rapid determination of synergy between beta-lactam antibiotics and clavulanic acid is discussed.

Adenosine Triphosphate↗