Biomedical subjects

D M Walsh

Publications and source records attributed to D M Walsh.

At least 37 records · Page 2Linked to original sources

PubMed2000

Delayed onset muscle soreness: effect of an ischaemic block upon mechanical allodynia in humans.

The current study, for which ethical approval was obtained, was designed to assess the extent to which the tenderness or mechanical allodynia observed in delayed onset muscle soreness (DOMS) might be mediated by large diameter myelinated nerve fibres. Healthy human volunteers were recruited and randomly allocated to one of three groups: Normal-Control, Ischaemic-Control, and Test-DOMS (total n=21; n=7 in each group). In the Normal-Control group, subjects attended on a single occasion for assessment of mechanical pain threshold (MPT) at standardized sites over the biceps brachii using a pressure algometer for a period of 20 min. In both remaining groups, ischaemia was induced in subjects' non-dominant upper limbs by elevation of the limb, followed by application of a sphygmomanometer cuff at a pressure of 250 mmHg. Throughout the period of the block (20-40 min), sharp/blunt sensation was assessed at regular intervals. MPT was assessed upon inflation of the cuff and reassessed at 10 min intervals until deflation. In the two ischaemic block groups, current level of pain was also monitored using a computerized visual analogue scale (VAS) at the beginning and end of the procedure. Subjects in the Test-DOMS group attended 48 h prior to ischaemic block for induction of DOMS using a standardized regime of eccentric exercise, but thereafter were treated in exactly the same manner as the Ischaemic-Control group. Results showed a significant (P<0.05; ANOVA) increase in MPT in the Test-DOMS group by the 20 min point, corresponding to a 'normalization' of MPT; loss of the ability to distinguish between sharp/blunt sensation accompanied such changes. Parallel increases in reported pain were seen in both groups undergoing ischaemic block, indicating that the procedure did not alter nociception. While not definitive, these results suggest that altered processing of activity in large diameter (myelinated) afferents might underlie the mechanical allodynia observed in DOMS; thus, this is an area which warrants further investigation.

Adolescent↗

PubMed2000

A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils.

We report here that a monomeric de novo designed alpha-helix-turn-alpha-helix peptide, alpha t alpha, when incubated at 37 degrees C in an aqueous buffer at neutral pH, forms nonbranching, protease resistant fibrils that are 6-10 nm in diameter. These fibrils are rich in beta-sheet and bind the amyloidophilic dye Congo red. alpha t alpha fibrils thus display the morphologic, structural, and tinctorial properties of authentic amyloid fibrils. Surprisingly, unlike fibrils formed by peptides such as the amyloid beta-protein or the islet amyloid polypeptide, alpha t alpha fibrils were not toxic to cultured rat primary cortical neurons or PC12 cells. These results suggest that the potential to form fibrils under physiologic conditions is not limited to those proteins associated with amyloidoses and that fibril formation alone is not predictive of cytotoxic activity.

Amino Acid Sequence↗

PubMed2000

The effect of interferential therapy upon cutaneous blood flow in humans.

The aim of the current controlled and blinded study was to investigate the effect of various interferential current frequencies upon cutaneous blood flow in humans using laser Doppler flowmetry, in an attempt to define the physiological mechanisms involved. Following approval from the university's ethical committee, 50 healthy volunteers (25 male, 25 female; age 18-34 years) were randomly allocated into one of five experimental groups: (i) control; neither suction nor interferential current was applied, (ii) placebo; suction only was applied, (iii) IFT 1; 10-100 Hz beat frequency applied, (iv) IFT 2; 80-100 Hz beat frequency applied, and (v) IFT 3; 10-20 Hz beat frequency applied. In the IFT groups, interferential currents were applied through four suction electrodes positioned to target the quadriceps femoris muscle. The following parameters were used in all IFT groups: 125 micros pulse duration, 4 kHz carrier frequency and a 6/6 sweep. In IFT groups 1 and 2 only, the rotating vector system was made active. Ambient and skin temperatures were measured concomitantly. Repeated-measures ANOVA showed a significant difference between groups (P=0.0361) and over time (P=0.0001) for blood flow data; one-factor ANOVA showed a significant increase in blood flow in the IFT 3 group (10-20 Hz) when compared to all experimental groups at 12 min (P=0.0156). In addition, at 21 min, there were significant differences between the IFT 3 group and all other groups except control (P=0.0213). Statistical analysis of skin temperature data demonstrated significant differences over time (P=0.0001) and a significant interactive effect (P=0.0022), with no significant differences observed between groups. These findings provide some evidence of a putative vasodilatory effect caused by interferential current therapy when applied through suction electrodes at a modulated frequency of 10-20 Hz.

Adolescent↗

PubMed2000

The effect of high- and low-frequency transcutaneous electrical nerve stimulation upon cutaneous blood flow and skin temperature in healthy subjects.

The reported non-analgesic effects of transcutaneous electrical nerve stimulation (TENS) include alterations to the local circulation; however, research in this area has produced equivocal findings. In the present study, the effect of low- (4 Hz) and high-frequency (110 Hz) TENS on forearm skin blood perfusion was assessed using laser Doppler flowmetry. The effect on skin temperature was also assessed using a skin thermistor. Thirty healthy human volunteers were recruited and randomly assigned to a control or one of the two treatment groups. TENS was applied to the skin overlying the median nerve under double-blind conditions for 15 min. Blood flow and skin temperature readings were recorded pre-TENS, during TENS application and continued for 15 min post-TENS application. Analysis of results showed significant increases in blood perfusion during the treatment period in the low-frequency group when compared to the other two groups (P = 0.0106; ANOVA). No significant changes in skin temperature were observed. The results of this study demonstrate that low-frequency TENS produces a local increase in cutaneous blood flow.

Female↗

PubMed2000

Study of the effects of various transcutaneous electrical nerve stimulation (TENS) parameters upon the RIII nociceptive and H-reflexes in humans.

Despite over two decades of clinical use, the neurophysiological and anti-nociceptive effects of transcutaneous electrical nerve stimulation (TENS) have yet to be definitively described. The current study was designed to examine the effect of TENS on the RIII nociceptive reflex elicited in healthy human subjects; the H-reflex was measured concomitantly to monitor changes in alpha-motoneuron excitability. Following approval from the university's ethical committee, 50 healthy human volunteers (25 male and 25 female) participated in the study. The subjects ranged in age from 18 to 30 years (mean 22, SD 3). Subjects were randomly allocated equally to a control group or one of four TENS groups. In the TENS groups, stimulation was applied for a total of 15 min over the sural nerve in the left leg. Ipsilateral RIII and H-reflexes were recorded five times during the 45 min experimental period. In addition, subjects also rated pain associated with the RIII reflex using a computerized visual analogue scale (VAS). Statistical analysis using two-way repeated-measures ANOVA showed no differences between groups for H-reflex, RIII reflex nor VAS data. These results suggest that TENS does not significantly affect either of the two reflexes, at least using the parameters and application time in the current study.

Adolescent↗

PubMed2000

Managing delayed-onset muscle soreness: lack of effect of selected oral systemic analgesics.

OBJECTIVE: To investigate the efficacy of commonly available analgesics in the management of delayed-onset muscle soreness over an 11-day period. DESIGN: Double-blind, placebo-controlled randomized trial. SETTING: University laboratory. PARTICIPANTS: Sixty healthy volunteers (30 men, 30 women) with no current arm pain or pathology completed the experimental procedure. INTERVENTIONS: Subjects were randomly allocated to one of five experimental groups: control; placebo; aspirin (900 mg); codeine (60 mg); and paracetamol (1000 mg) (n = 12 in all groups). Delayed soreness was induced in the nondominant elbow flexors using a standardized exercise protocol of repeated eccentric contractions. MAIN OUTCOME MEASURES: Pain (visual analogue scale; McGill pain questionnaire [MPQ]), range of extension, flexion and resting angle (universal goniometer), and mechanical pain threshold (pressure algometer). Measurements were taken before and after drug administration each day, except for the MPQ, which was completed on the first and third days of the experiment. RESULTS: Analysis of results using repeated-measures analysis of variance and relevant post hoc tests provided no evidence of the effectiveness of any of the preparations. CONCLUSION: There is no beneficial effect from the medications, at least at the doses stated, in the management of delayed-onset muscle soreness.

Acetaminophen↗

PubMed2000

Effect of acupuncture upon experimentally induced ischemic pain: a sham-controlled single-blind study.

OBJECTIVE: To investigate the hypoalgesic effect of true and sham acupuncture upon experimentally induced ischemic pain. DESIGN: Human volunteers (n = 60) were required to attend two sessions for pain induction using a submaximal effort tourniquet technique; on the first occasion, baseline pain scores were recorded and on the second, 48 hours later, subjects were randomly allocated to one of five groups: Control, Treatment Groups 1 or 2, or Placebo Groups 1 or 2. SUBJECTS: Healthy human volunteers. INTERVENTION: In all the Treatment and Placebo Groups, subjects received some form of needle acupuncture 15 minutes before, and 5 minutes during, the pain induction procedure on the second day. Treatment Group 1 received acupuncture on acupuncture points situated distal to the tourniquet, whereas Treatment Group 2 received acupuncture on acupuncture points situated proximal to the tourniquet. In Placebo Groups 1 and 2, subjects received 'sham' acupuncture either on nonacupuncture points (Placebo Group 1) or on acupuncture points (Placebo Group 2) using (standardized) minimal levels of stimulation. A licensed acupuncturist who was not involved in data collection and analyses carried out all treatments. OUTCOME MEASURES: Pain was assessed using a computerized visual analog scale (VAS) and a McGill Pain Questionnaire (MPQ). RESULTS: Analysis of VAS scores using ANOVA revealed no significant differences between groups (e.g., VAS sum of differences data (mean +/- SEM): Treatment Group 1: 90+/-47, Treatment Group 2: 187+/-56, Placebo Group 1: 152+/-40, Placebo Group 2: 121+/-42, CONTROLS: 46+/-24, p>0.05). Analysis of MPQ percentage difference scores using one-way ANOVA revealed some isolated effects in the subjective descriptors and the Pain Rating Index, both for Treatment Group 2 and Placebo Group 2, proving them superior to any of the other groups. CONCLUSION: The results of the study provide no convincing evidence for a superior hypoalgesic effect of acupuncture compared with "sham" procedures on this model of experimental pain.

Acupuncture Therapy↗

PubMed2000

An improved method of preparing the amyloid beta-protein for fibrillogenesis and neurotoxicity experiments.

Synthetic amyloid beta-protein (A beta) is used widely to study fibril formation and the physiologic effects of low molecular weight and fibrillar forms of the peptide on cells in culture or in experimental animals. Not infrequently, conflicting results have arisen in these studies, in part due to variation in the starting conformation and assembly state of A beta. To avoid these problems, we sought a simple, reliable means of preparing A beta for experimental use. We found that solvation of synthetic peptide with sodium hydroxide (A beta x NaOH), followed by lyophilization, produced stocks with superior solubility and fibrillogenesis characteristics. Solubilization of the pretreated material with neutral buffers resulted in a pH transition from approximately 10.5 to neutral, avoiding the isoelectric point of A beta (pI approximately 5.5), at which A beta precipitation and aggregation propensity are maximal. Relative to trifluoroacetate (A beta x TFA) or hydrochloric acid (A beta x HCl) salts of A beta, yields of "low molecular weight A beta" (monomers and/or dimers) were improved significantly by NaOH pretreatment. Time-dependent changes in circular dichroism spectra and Congo red dye-binding showed that A beta x NaOH formed fibrils more readily than did the other A beta preparations and that these fibrils were equally neurotoxic. NaOH pretreatment thus offers advantages for the preparation of A beta for biophysical and physiologic studies.

Amino Acid Sequence↗

PubMed1999

Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is thought to be caused in part by the age-related accumulation of amyloid beta-protein (Abeta). The presence of neuritic plaques containing abundant Abeta-derived amyloid fibrils in AD brain tissue supports the concept that fibril accumulation per se underlies neuronal dysfunction in AD. Recent observations have begun to challenge this assumption by suggesting that earlier Abeta assemblies formed during the process of fibrillogenesis may also play a role in AD pathogenesis. Here, we present the novel finding that protofibrils (PF), metastable intermediates in amyloid fibril formation, can alter the electrical activity of neurons and cause neuronal loss. Both low molecular weight Abeta (LMW Abeta) and PF reproducibly induced toxicity in mixed brain cultures in a time- and concentration-dependent manner. No increase in fibril formation during the course of the experiments was observed by either Congo red binding or electron microscopy, suggesting that the neurotoxicity of LMW Abeta and PF cannot be explained by conversion to fibrils. Importantly, protofibrils, but not LMW Abeta, produced a rapid increase in EPSPs, action potentials, and membrane depolarizations. These data suggest that PF have inherent biological activity similar to that of mature fibrils. Our results raise the possibility that the preclinical and early clinical progression of AD is driven in part by the accumulation of specific Abeta assembly intermediates formed during the process of fibrillogenesis.

Amyloid beta-Peptides↗

PubMed1999

Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates.

Alzheimer's disease is characterized by extensive cerebral amyloid deposition. Amyloid deposits associated with damaged neuropil and blood vessels contain abundant fibrils formed by the amyloid beta-protein (Abeta). Fibrils, both in vitro and in vivo, are neurotoxic. For this reason, substantial effort has been expended to develop therapeutic approaches to control Abeta production and amyloidogenesis. Achievement of the latter goal is facilitated by a rigorous mechanistic understanding of the fibrillogenesis process. Recently, we discovered a novel intermediate in the pathway of Abeta fibril formation, the amyloid protofibril (Walsh, D. M., Lomakin, A., Benedek, G. B., Condron, M. M., and Teplow, D. B. (1997) J. Biol. Chem. 272, 22364-22372). We report here results of studies of the assembly, structure, and biological activity of these polymers. We find that protofibrils: 1) are in equilibrium with low molecular weight Abeta (monomeric or dimeric); 2) have a secondary structure characteristic of amyloid fibrils; 3) appear as beaded chains in rotary shadowed preparations examined electron microscopically; 4) give rise to mature amyloid-like fibrils; and 5) affect the normal metabolism of cultured neurons. The implications of these results for the development of therapies for Alzheimer's disease and for our understanding of fibril assembly are discussed.

Alzheimer Disease↗

PubMed1999

Lack of effect of combined low intensity laser therapy/phototherapy (CLILT) on delayed onset muscle soreness in humans.

BACKGROUND AND OBJECTIVES: This study, which was approved by the University's Ethical committee, was conducted to investigate the effectiveness of Combined Low Intensity Laser Therapy/Phototherapy (CLILT) in alleviating the signs and symptoms of Delayed Onset Muscle Soreness (DOMS) over an 11-day period. STUDY DESIGN/MATERIALS AND METHODS: Thirty-six subjects (18 M: 18 F) were randomly allocated, under strictly controlled double-blind conditions, to one of three experimental conditions: Control, Placebo, and CLILT (660-950 nm; 11 J/cm2; pulsed at 73 Hz). DOMS was induced in a standardised fashion in the non-dominant elbow flexors using repeated eccentric contractions until exhaustion was reached. Subjects returned on five consecutive days, and two days during the following week, for treatment according to group, and assessment of outcome variables including range of motion, pain, and tenderness. RESULTS: While analysis of results using repeated measures and one factor ANOVA with post-hoc tests showed significant changes in all variables over time (P < 0.05) as a result of the induction procedure, there were no significant differences observed between groups. CONCLUSIONS: CLILT failed to show any beneficial treatment effect on DOMS, at least at the parameters used here. These results therefore provide no evidence for the claimed biostimulating effects of such therapy.

Adult↗

PubMed1999

Comparative analgesic effects of H-wave therapy and transcutaneous electrical nerve stimulation on pain threshold in humans.

OBJECTIVE: To assess the comparative analgesic efficacy of H-wave therapy (HWT) and transcutaneous electrical nerve stimulation (TENS) using a mechanical model of pain threshold measurement. STUDY DESIGN: Forty-eight healthy human volunteers (24 women, 24 men) were recruited and randomly assigned into one of six experimental groups; control, HWT (placebo, 2Hz, or 60Hz), or TENS (placebo or 110Hz). For each subject, mechanical pain threshold (MPT) measurements were recorded at three standardized recording points marked on the dorsal web space of the dominant hand. Two MPT measurements were recorded at each point at the following time intervals: before treatment was initiated (baseline), after each of three consecutive 10-minute periods of stimulation (HWT or TENS), and at four intervals within 30 minutes after stimulation. In the control and placebo groups MPT measurements were recorded at similar time intervals. RESULTS: Difference scores, calculated from patients' baseline values, were analyzed by ANOVA for each of the three recording points. Although results showed a significant increase in MPT levels in all three stimulation groups when compared with their relative placebo (indicating a hypoalgesic effect), no differences were observed between the different modalities or HWT frequencies. Significant hypoalgesia continued for 5 minutes after stimulation. CONCLUSION: The findings showed that HWT and TENS provided localized hypoalgesia during stimulation and for up to 5 minutes after it. No frequency- or modality-specific effects were observed between the groups.

Adult↗

PubMed1999

Delayed onset muscle soreness: lack of effect of therapeutic ultrasound in humans.

OBJECTIVE: To investigate the effects of two dosages of pulsed ultrasound therapy (1 MHz, spatial averaged peak intensity 0.8 W/cm2, mark space ratio of 1:4) on acute-stage delayed onset muscle soreness (DOMS). DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING: Laboratory of a university physiotherapy department. PARTICIPANTS: Forty-eight healthy volunteers (24 men, 24 women) with no arm pathology or pain at the time of the study. INTERVENTIONS: Subjects were randomly allocated to one of four treatment groups: control, placebo (sham insonation), low-dosage pulsed ultrasound (mean dosage 172.8 J), or high-dosage pulsed ultrasound (mean dosage 345.6 J). DOMS was induced in the nondominant elbow flexors in a standardized fashion through repeated eccentric exercise until exhaustion. MAIN OUTCOME MEASURES: Elbow extension, flexion, and resting angles (universal goniometer), pain (visual analogue scale), mechanical pain threshold/tenderness (pressure algometer), and a McGill pain questionnaire. Measurements were taken before and after treatment each day except for the McGill pain questionnaire, which was completed at the end of the trial. RESULTS: Significant differences were seen between groups in relation to range of flexion (p = .0032), with the control group losing least range of flexion. There were no other significant differences between the groups. CONCLUSION: No convincing evidence was found to support the use of pulsed ultrasound therapy in the management of DOMS at the parameters discussed here.

Adult↗

PubMed1999

The effect of high- and low-frequency H-wave therapy upon skin blood perfusion: evidence of frequency-specific effects.

The current study was designed to assess the putative physiological effects of H-wave therapy (HWT, a mode of therapeutic electro-stimulation) on skin blood flow in humans and to determine the relevance of frequency to any such effects. Laser Doppler flowmetry was used to record changes in blood perfusion on the dominant forearm of healthy human volunteers (n=36), who were each assigned, under randomized double blind conditions, to one of three experimental groups: placebo or HWT at 2 or 60 Hz. HWT stimulation was applied for 20 min, during which time concomitant skin temperature was recorded using three surface skin thermistors. Statistical analysis of perfusion measurement and skin temperature changes pre-, during and for up to 18 min post-HWT stimulation showed a highly significant increase in skin blood flow in the 2 Hz group when compared to placebo and 60 Hz (P<or/ = 0.01). This was associated with a significant increase in skin temperature during the period of stimulation (P<or/ = 0.05). No such differences were observed in the 60 Hz group. These results provide evidence that low-frequency HWT may produce direct localized effects on cutaneous blood flow, a finding relevant for clinicians working in the field of tissue repair.

Adolescent↗

PubMed1998

Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation.

Excessive cerebral accumulation of the 42-residue amyloid beta-protein (Abeta) is an early and invariant step in the pathogenesis of Alzheimer's disease. Many studies have examined the cellular production of Abeta from its membrane-bound precursor, including the role of the presenilin proteins therein, but almost nothing is known about how Abeta is degraded and cleared following its secretion. We previously screened neuronal and nonneuronal cell lines for the production of proteases capable of degrading naturally secreted Abeta under biologically relevant conditions and concentrations. The major such protease identified was a metalloprotease released particularly by a microglial cell line, BV-2. We have now purified and characterized the protease and find that it is indistinguishable from insulin-degrading enzyme (IDE), a thiol metalloendopeptidase that degrades small peptides such as insulin, glucagon, and atrial natriuretic peptide. Degradation of both endogenous and synthetic Abeta at picomolar to nanomolar concentrations was completely inhibited by the competitive IDE substrate, insulin, and by two other IDE inhibitors. Immunodepletion of conditioned medium with an IDE antibody removed its Abeta-degrading activity. IDE was present in BV-2 cytosol, as expected, but was also released into the medium by intact, healthy cells. To confirm the extracellular occurrence of IDE in vivo, we identified intact IDE in human cerebrospinal fluid of both normal and Alzheimer subjects. In addition to its ability to degrade Abeta, IDE activity was unexpectedly found be associated with a time-dependent oligomerization of synthetic Abeta at physiological levels in the conditioned media of cultured cells; this process, which may be initiated by IDE-generated proteolytic fragments of Abeta, was prevented by three different IDE inhibitors. We conclude that a principal protease capable of down-regulating the levels of secreted Abeta extracellularly is IDE.

Alzheimer Disease↗

PubMed1998

The influence of the central region containing residues 19-25 on the aggregation properties and secondary structure of Alzheimer's beta-amyloid peptide.

Alzheimer's beta-amyloid peptide (Abeta) is a 39- to 43-amino-acid peptide that is the major component of neuritic plaques found in Alzheimer's disease (AD). The central region of Abeta plays a crucial role in many of its properties, including aggregation, neurotoxicity, proteolytic processing and interactions with other proteins, such as apolipoprotein E. Two mutations in this region, Ala21-->Gly and Glu22-->Gln, give rise to early onset forms of disease. We have studied several peptides based on the central region of Abeta in order to clarify the influence of specific amino acid residues on physicochemical behaviour. To avoid difficulties due to oxidation of Met35, the latter was replaced by the amino acid isostere, norleucine (Ahx), giving [Ahx35]Abeta-(25-35)-amide as a prototype structure. To this prototype, addition of pairs of amino acid residues from the sequence of Abeta, forming the corresponding 23-, 21- and 19-35 derivatives, resulted in peptides that aggregated to form fibrils of diameter 6-10 nm. The rate of aggregation was more rapid as peptide length increased. Circular dichroism spectra of aged solutions of peptides revealed that aggregation was accompanied by a transition from random structure to beta sheet for some, but not all, peptides. The mutation from Ala to Gly at position 21 increased the rate of aggregation and altered the tendency to adopt secondary structure in the direction away from alpha helix and towards beta sheet. In individuals with the Ala21-->Gly mutation, these results would suggest that truncated species with N-termini in the region containing residues 17-20 would be more amyloidogenic than the wild type homologues.

Alzheimer Disease↗

PubMed1998

Oligomerization of endogenous and synthetic amyloid beta-protein at nanomolar levels in cell culture and stabilization of monomer by Congo red.

Amyloid beta-proteins (A beta) are proteolytic fragments of the beta-amyloid precursor protein (beta APP) that are secreted by mammalian cells throughout life but also accumulate progressively as insoluble cerebral aggregates in Alzheimer's disease (AD). Because mounting evidence indicates that A beta aggregation and deposition are early, critical features of AD leading to neurotoxicity, many studies of A beta aggregation have been conducted using synthetic peptides under generally nonphysiological conditions and concentrations. We recently described the oligomerization of A beta peptides secreted by beta APP-expressing cells at low nanomolar (20-30 ng/mL) levels into sodium dodecyl sulfate- (SDS-) stable oligomers of 6-16 kDa. Here, we extensively characterize this in vitro system and show that the amyloid binding dye, Congo red, acts to markedly decrease oligomer/monomer ratios by stabilizing the 4 kDa A beta monomers (ID50 approximately equal to 3.4 microM). Addition of radioiodinated synthetic A beta 1-40 to the cultures or to their conditioned media at physiological concentrations (0.25-2.5 nM) reveals that it undergoes progressive aggregation into SDS-stable oligomers of 6-25 kDa during brief (approximately 4 h) incubation at 37 degrees C, and this is inhibitable by Congo red. The level of A beta oligomers can be quantitated in the Chinese hamster ovary (CHO) conditioned medium by size-exclusion chromatography as well as by SDS-polyacrylamide gel electrophoresis (PAGE), and comparison of these two methods suggests that aggregation of A beta into higher molecular weight polymers that are not detectable by SDS-PAGE occurs in the cultures. We conclude that both endogenous and synthetic A beta can assemble into stable oligomers at physiological concentrations in cell culture, providing a manipulable system for studying the mechanism of early A beta aggregation and identifying inhibitors thereof under biologically relevant conditions.

Amyloid beta-Peptides↗

PubMed1998

Transcutaneous electrical nerve stimulation: effect on peripheral nerve conduction, mechanical pain threshold, and tactile threshold in humans.

OBJECTIVES: To investigate the effect of different transcutaneous electrical nerve stimulation (TENS) parameters on nerve conduction in the human superficial radial nerve and on peripheral mechanical pain threshold (MPT) and tactile threshold (TT), and to further the current knowledge of the neurophysiologic effects of TENS. STUDY DESIGN: Fifty healthy human subjects were randomly allocated in equal numbers to a control group or one of four TENS groups to receive electrical stimulation consisting of four combinations of TENS pulse durations (50microsec and 200microsec) and frequencies (4Hz and 110Hz). In the TENS groups, TENS was applied under double-blind conditions for 15 minutes over the superficial radial nerve in the dominant forearm. Over a 1-hour period, compound action potentials, MPT readings, and TT readings were recorded bilaterally. RESULTS: Only one combination of TENS parameters (110Hz, 200microsec) effected consistent changes in all of the variables assessed, ie, TENS produced a significant increase in negative peak latency while simultaneously increasing both MPT and TT. CONCLUSION: The findings from this study suggest that at least part of TENS-mediated hypoalgesia is a consequence of a direct peripheral effect of TENS, although a "central" effect may not be excluded.

Adult↗