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Fourier transform infrared/Raman differentiation and characterization of cis- and trans-2,5-dimethoxy-4,beta-dimethyl-beta-nitrostyrenes: precursors to the street drug STP.

Fourier transform Raman and infrared spectra of pure cis(Z)- and trans(E)-2,5-dimethoxy-4,beta-dimethyl-beta-nitrostyrene (precursors of the psychotomimetic street drug STP or DOM) were recorded in the solid state. The spectra show characteristic features of the ethylene moiety and of the aryl and nitro substituents which permit ready differentiation and identification of these isomers. A very strong Raman line at 1670 cm-1 from the cis isomer for the C=C stretching mode, in comparison with a strong Raman line at 1641 cm-1 for the trans isomer, affords primary differentiation of these substances. A second characteristic, of both the Raman and infrared (IR) spectra, is that the frequency of the strong symmetric nitro (NO2) stretching band is about 40 cm-1 higher in the cis (1346 cm-1) than the trans isomer (1301 cm-1). All major IR and Raman bands are reported and given vibrational assignments.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Unwelcome guests with master keys: how HIV enters cells and how it can be stopped.

HIV entry to host cells begins with binding of the viral envelope protein to CD4 molecules on the host cell surface. This binding initiates conformational changes in the envelope protein that result in binding to a coreceptor (CCR5 or CXCR4), exposure of a previously hidden domain in the viral protein, insertion of a viral fusion peptide into the host-cell membrane and fusing the viral and cell membranes. Each of these steps provides an opportunity for intervention to prevent viral entry, and a number of agents targeting these steps are in development. Studies of coreceptor inhibitors and fusion inhibitors have indicated the presence of host and viral factors that can result in variability of antiretroviral effect. Improved understanding of these factors will help to guide clinical use of these new agents. This article summarizes a presentation by Robert W. Doms, MD, PhD, at the International AIDS Society-USA course in Chicago in May 2004.

Anti-HIV Agents↗

Histopathology and growth rate of interval breast carcinoma. Characterization of different subgroups.

BACKGROUND: Interval breast cancers are defined as carcinomas occurring within 2 years after a negative screening Distinction has to made between cancers existent at the time of screening but missed for some reason, and fast-growing incident cancers. This is important because the natural history and the implications for the treatment of the patient might differ. METHODS: Radiologic and histopathologic characteristics were assembled for 104 interval cancers diagnosed within the DOM project, the Utrecht program for the early detection of breast cancer. At a mammographic review for 27 cases, signs of malignant or benign tumor were found (missed cases). For 77 cases no radiologic signs were present on review. Twenty of these cases had a mitotic rate of > 3 and a high tumor growth rate (mean doubling time: 51 days). This combination seemed implausible, therefore, it was thought hypothesized that these tumors were most likely present, although radiologically invisible (masked), at the time of screening. The remaining cases (n = 57) were classified as true interval cancers and further divided into 14 fast-growing cases (mitotic rate > or = 3/high-power field [HPF]) and 43 cases with an intermediate growth rate (mitotic rate < 3/HPF). RESULTS: Factors associated with the masking of tumors were the histologic tumor type, absence of microscopic calcifications, and presence of dense breast tissue. Fast-growing tumors were characterized by a young patient age, absence of microscopic calcifications, and a high percentage of regional lymph node positive tumors. The 5-year survival probability was 100% for missed cases, 70% for masked cases, 80% for cases with an intermediate growth rate, and 54% for fast-growing cases. CONCLUSIONS: It is possible to separate interval breast cancers in true interval cases and cases (most likely) existent at the time of screening. Part of this last group is invisible by mammography (masked).

Adult↗

Optimal allele-sharing statistics for genetic mapping using affected relatives.

The choice of allele-sharing statistics can have a great impact on the power of robust affected relative methods. Similarly, when allele-sharing statistics from several pedigrees are combined, the weight applied to each pedigree's statistic can affect power. Here we describe the direct connection between the affected relative methods and traditional parametric linkage analysis, and we use this connection to give explicit formulae for the optimal sharing statistics and weights, applicable to all pedigree types. One surprising consequence is that under any single gene model, the value of the optimal allele-sharing statistic does not depend on whether observed sharing is between more closely or more distantly related affected relatives. This result also holds for any multigene model with loci unlinked, additivity between loci, and all loci having small effect. For specific classes of two-allele models, we give the most powerful statistics and optimal weights for arbitrary pedigrees. When the effect size is small, these also extend to multigene models with additivity between loci. We propose a useful new statistic, S(rob dom), which performs well for dominant and additive models with varying phenocopy rates and varying predisposing allele frequency. We find that the statistic S(_#alleles), performs well for recessive models with varying phenocopy rates and varying redisposing allele frequency. We also find that for models with large deviation from null sharing, the correspondence between allele-sharing statistics and the models for which they are optimal may also depend on which method is used to test for linkage.

Alleles↗

Biochemical composition, metabolism, and amino acid transport in planula-larvae of the soft coral Heteroxenia fuscescens.

We determined the monthly percentage of biochemical components in planulae of the soft coral Heteroxenia fuscescens, for a 3-year period, and evaluated the findings in relation to seasonal fluctuations in water temperature. We determined the biochemical profile and metabolic rate of aging planulae and examined the possible absorption of dissolved organic material (DOM) from the water by the planulae. Our study is the first to present a long-term biochemical profile of planulae. They contained an average of 2.2% ash, 51.5% lipid, 33.6% protein, and 1.3% carbohydrate. Calculation of the average energetic content of a planula revealed a value of 1. 63 J planula(-1). Significant seasonal differences in planulae weight were noted between the summer and the other seasons. A significant decrease (41%) from the initial weight, 0.029 mg, took place in the planulae dry weight within 15 days. Significant decreases over time were also found in lipid (50%) and carbohydrate (83%) concentration but not in protein (20%). Metabolic rates of a planula was 0.06 microl O(2) planula(-1) hr(-1). The study shows for the first time that a soft coral planulae can take up dissolved free amino acids from seawater. Even though each of the amino acids was initially present at equimolar concentrations, there was a much faster uptake for the neutral, nonpolar amino acids, than for polar and basic ones. The potential contribution to the metabolic demand of planulae, from the uptake of amino acids, is estimated to be 11%. It is suggested that this uptake does not appear to be due to energetic considerations, but may have a more significant impact on their nitrogen budget.

Amino Acids↗

Obesity and subcutaneous fat patterning in relation to breast cancer in postmenopausal women participating in the Diagnostic Investigation of Mammary Cancer Project.

Associations of body fat and body fat distribution with breast cancer were studied in 16,355 postmenopausal women with a natural menopause, aged 49 to 68 years, participating in a breast cancer screening project (the Diagnostic Investigation of Mammary Cancer [DOM] project in Utrecht, The Netherlands). One hundred nineteen women had breast cancer detected at first screening. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness. No relationship between fat distribution and breast cancer was found. After adjustment for age, women in the highest quartile of Quetelet's index (QI) (weight/height2) had an odds ratio of 1.65 (95% confidence interval [CI], 0.97 to 2.81) compared with women in the the lowest quartile (test for trend, P less than 0.05). For subscapular skinfold and triceps skinfold, the odds ratios were 2.23 (95% CI, 1.28 to 3.91) and 2.01 (95% CI, 1.21 to 3.32), respectively, comparing the highest with the lowest quartile. The authors conclude that in postmenopausal women, overall obesity is associated with increased risk of breast cancer, whereas fat distribution, as measured by contrasting groups of subscapular and triceps skinfold thicknesses, is not related to breast cancer.

Adipose Tissue↗

A Fourier analysis approach for capillary polarimetry.

A new method of fringe interrogation based on Fourier analysis was implemented and tested for a capillary polarimetry detector. It has significant advantages over the previously employed depth of modulation (DOM) approach, including speed and alignment insensitivity. The new and old methods were compared using a set of interference fringes typically used to facilitate nanoliter volume polarimetric determinations. Polarimetric response was calculated with both methods over the range from 0 degrees to 180 degrees. The results were found to be in good agreement with Malus Law and indicate that an fast Fourier transform (fft) could be used for real-time capillary scale polarimetry in a probe volume of 40 nL.

Electrophoresis, Capillary↗

Hoxb3 vagal neural crest-specific enhancer element for controlling enteric nervous system development.

The neural and glial cells of the intrinsic ganglia of the enteric nervous system (ENS) are derived from the hindbrain neural crest at the vagal level. The Hoxb3 gene is expressed in the vagal neural crest and in the enteric ganglia of the developing gut during embryogenesis. We have identified a cis-acting enhancer element b3IIIa in the Hoxb3 gene locus. In this study, by transgenic mice analysis, we examined the tissue specificity of the b3IIIa enhancer element using the lacZ reporter gene, with emphasis on the vagal neural crest cells and their derivatives in the developing gut. We found that the b3IIIa-lacZ transgene marks only the vagal region and not the trunk or sacral region. Using cellular markers, we showed that the b3IIIa-lacZ transgene was expressed in a subset of enteric neuroblasts during early development of the gut, and the expression was maintained in differentiated neurons of the myenteric plexus at later stages. The specificity of the b3IIIa enhancer in directing gene expression in the developing ENS was further supported by genetic analysis using the Dom mutant, a spontaneous mouse model of Hirschsprung's disease characterized by the absence of enteric ganglia in the distal gut. The colonization of lacZ-expressing cells in the large intestine was incomplete in all the Dom/b3IIIa-lacZ hybrid mutants we examined. To our knowledge, this is the only vagal neural crest-specific genetic regulatory element identified to date. This element could be used for a variety of genetic manipulations and in establishing transgenic mouse models for studying the development of the ENS.

Animals↗

Polymorphisms in the genes involved in the arachidonic acid-pathway, fish consumption and the risk of colorectal cancer.

The objective of this study on colorectal cancer was to investigate the associations between SNPs in the genes involved in the arachidonic acid (AA)-pathway, their haplotypes and colorectal cancer. Moreover, interactions between SNPs and fish consumption were considered. In this study, a total of 508 cases and 772 controls were included, originating from 2 prospective cohorts, the Monitoring Project on Cardiovascular Disease Risk Factors (PPHV) and Diagnostisch Onderzoek Mammacarcinoom (DOM). Genotypes of 23 SNPs in 7 candidate genes were determined and the modifying effect of fish consumption was considered. A protective effect of the minor allele of SNP V102V in PTGS2 was observed (odds ratio (OR), 0.37; 95% confidence intervals (CI), 0.16-0.87). The haplotype representing this allele showed a weaker inverse association, indicating that 2 alleles are necessary to obtain this protective effect. Fish consumption data was available for 209 cases and 418 controls. Increased fish consumption was inversely associated with cancer, although not significant (OR, 0.83; 95% CI, 0.57-1.20). Despite the substantial reductions in cancer risk for some genotypes in combination with high fish intake, no significant interactions between any SNP studied and fish consumption were observed. We have previously described an association between colorectal adenomas and SNP V102V in PTGS2 and have now confirmed this association for colorectal adenocarcinomas. Fish consumption of once a week or more might protect against colorectal cancer, but no significant interactions with SNPs in the genes involved in the AA-pathway could be detected within the study.

Adult↗

Inherited sex reversal in mice: identification of a new primary sex-determining gene.

We present evidence that the inbred mouse strain C57BL/6J (B6) differs from Mus domesticus (DOM) at a locus involved in gonad determination and development as well as at the testis-determining locus on the Y chromosome (Tdy). This newly identified gene is named testis-determining, autosomal-1 (tda-1). Although the inheritance of tda-1 suggests it is located on an autosome, its location on the X and Y chromosome in their pairing-recombination region is not excluded. When mice are homozygous for the C57BL/6J-derived tda-1 allele (tda-1B6) and carry the Y chromosome from M. domesticus, they develop as true hermaphrodites or, more rarely, as females. In contrast, when they are homozygous Tda-1DOM/Tda-1DOM or heterozygous Tda-1/DOMtda-1B6 and carry a B6-derived or M. domesticus-derived Y chromosome they develop as normal males. A simple genetic model is presented that integrates proposed steps in gonad determination and the results from genetic experiments reported here. In addition, arguments are presented for the existence of an ovary-determining gene.

Animals↗

Using a simple high-performance liquid chromatography separation and fraction collection methodology to achieve compound-specific isotopic analysis for dissolved organic compounds.

A new application for the quantitative and isotopic analyses of dissolved inorganic and dissolved organic carbon compounds has been developed. Dissolved organic matter (DOM) in natural water samples can be separated on a high-performance liquid chromatography (HPLC) column and collected as fractions. Each discrete fraction can then be analyzed using the technique of St-Jean (Rapid Commun. Mass Spectrom. 2003; 17: 419-428) with a total inorganic carbon/total organic carbon (TIC/TOC) analyzer interfaced with a continuous-flow isotope ratio mass spectrometer. Experimental data using short-chain fatty acid standards (formic, acetic, and propionic acids) show that fraction recoveries of 100% are possible and that sample integrity is maintained. 13C-isotopic analyses of products prior to and subsequent to extraction and collection show no isotopic effects associated with the methodology, and errors are well within the accepted analytical uncertainty of the IRMS. Comparison of data from pure standards and organic-rich natural waters shows that quantitative analyses still need to be done with standards that more closely imitate the matrices of the samples, in order to acquire an appropriate calibration curve. Injections of organic-rich matrices on the HPLC column did not affect fraction recovery, nor did they create high background of partially retained organic compounds slowly released from the HPLC column, and hence 13C-isotopic results are relatively unaffected. The specific limitation on this methodology is the required use of carbon-free carrier solvents due to potential memory effects associated with the TIC/TOC analyzer. Further developments of this application could make routine compound-specific isotopic analyses (CSIA) for a wider range of organic materials possible.

Carbon Isotopes↗

Quality and quantity of DNA isolated from frozen urine in population-based research.

In several population-based studies in the past urine samples were collected and stored for future research. We set out to determine the reliability of using such samples for genotyping DNA markers in epidemiologic research. A source of DNA extracted from exfoliated nucleated cells in urine is provided by the DOM cohort, in which specimens were collected 15-25 years ago. We have examined the quality of the DNA in 48 of these samples by measuring the amount of DNA isolated and its ability to provide an adequate PCR template for amplicons of different lengths. MTHFR polymorphism was analyzed in 644 specimens to determine the inter- and intraobserver reproducibility. Although the DNA amount was variable, 26 to 89% of the samples, depending both on the length of the PCR amplicon and on PCR conditions, yielded a visible PCR product. The intra- and interobserver agreements were comparable (kappa 0.86 and 0.88, respectively). Our results demonstrate that frozen urine samples can be used for DNA typing studies in women after prolonged periods of storage, but with sometimes unpredictable results. Ultimately, the genotype success rate was 89.3%. Urine collection can be considered as a useful method of obtaining DNA in large cohort studies and other circumstances when blood samples cannot be obtained or have not been stored.

DNA↗

Characterisation of the major intrinsic protein (MIP) from bovine lens fibre membranes by electron microscopy and hydrodynamics.

The major intrinsic protein (MIP) from bovine lens fibre membranes has been purified from unstripped membranes using a single ion-exchange chromatography step (MonoS) in the non-ionic detergent octyl-beta-D-glucopyranoside (OG). SDS-PAGE has confirmed the purity of the preparation and thin-layer chromatographic analysis has shown that the protein is virtually lipid-free. To establish a stable and monodisperse protein sample, we exchanged OG with decyl-beta-D-maltopyranoside (DeM), another non-ionic detergent, by gel-filtration column chromatography. We conclude that the resulting protein/detergent complex is composed of four copies of MIP (a tetramer) and a detergent micelle. This conclusion is based on: (1) measurement of the weight-average molecular mass (Mw,app) of the protein moiety in the protein/detergent complex by sedimentation equilibrium; (2) measurement of the apparent molecular mass of the complexes formed by MIP in OG, in DeM, in dodecyl-beta-D-maltopyranoside (DoM) and in sodium dodecylsulphate (SDS) by gel filtration; (3) measurement of the apparent molecular mass of pure detergent micelles; (4) measurement of the predicted change in the molecular mass of the MIP/DeM complex after partial enzymatic proteolysis; and (5) measurement of the size and shape of the MIP/detergent complex by electron microscopy and single-particle analysis. Therefore, the tetragonal arrangement of MIP observed in both plasma membranes and junctional membranes in lens fibre cells is maintained in solution with non-ionic detergents.

Amino Acid Sequence↗

Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse neuromuscular junction.

Linalool is a monoterpene compound reported to be a major component of essential oils in various aromatic species. Several linalool-producing species are used in traditional medical systems. Among these is Aeolanthus suaveolens G. Dom (Labiatae) which is used as an anticonvulsant in the Brazilian Amazon. Psychopharmacological in vivo evaluation of linalool showed that this compound has dose-dependent marked sedative effects at the central nervous system (CNS), including hypnotic, anticonvulsant and hypothermic properties. It has been suggested that these neurochemical effects might be ascribed to the local anaesthetic activity of linalool. The present study reports an inhibitory effect of linalool on the acetylcholine (ACh) release and on the channel open time in the mouse neuromuscular junction. These findings could provide a rational basis to confirm the traditional medical use of linalool-producing plant species. Indeed, our data demonstrate some interactions in the modulation of the ACh release at the mouse neuromuscular junction, which are well correlated with the suggested molecular mechanisms. Linalool induced a reduction of the ACh-evoked release. The possibility that this effect could be ascribed to some interaction with pre-synaptic function is noteworthy. Moreover, the inhibitory effect induced on the kinetics of the miniature end-plate current decay demonstrates a local anaesthetic action, either on the voltage or on the receptor-activated channels.

Acetylcholine↗

Multidrug-resistance transporters.

P-glycoprotein was initially isolated due to its role in multidrug resistance to cancer chemotherapeutics. Recent work, however, makes it increasingly apparent that this transporter is also involved in the pharmacokinetics of many drugs. P-gp is strategically expressed in the luminal epithelial cells of organs often associated with drug absorption and disposition, for example, hepatocyte canalicular membrane, renal proximal tubules, and the intestinal mucosa. P-gp is also expressed in the endothelial cells comprising the blood-brain barrier. This localization clearly suggests the potential for this protein to serve as a protective mechanism against entry of toxic xenobiotics and also suggests that P-gp is well situated to participate in the removal of therapeutic agents. Numerous investigations with drugs such as digoxin, etoposide, cyclosporine, vinblastine, Taxol, loperamide, dom-peridone, and ondansteron demonstrate that P-gp has an important role in determining the pharmacokinetics of substrate drugs. Pharmacological modulation of P-gp function to increase drug bioavailability, both on a organismal and a cellular level, is one approach currently being explored to enhance therapeutic effectiveness. This approach is not without potential collateral consequences given the wide tissue distribution of P-gp. While animals deficient in P-gp are viable and without obvious abnormalities, the pharmacokinetics and toxic consequences of several compounds are significantly altered in these animals. Thus blockade of the protective P-gp barrier in humans may have adverse effects on substrate drugs. In particular, this situation may arise when several compounds which may be substrates compete for P-gp-mediated transport. Additional multidrug transporters, notably MRP and family members, have been identified and may also determine the fate of pharmaceuticals. Further understanding the physiological role of each of the multidrug transporters is critical for determining their role in pharmacokinetics and for evaluating the consequences of modification of their activities. Such information is also important in the development of novel drugs which may be substrates for these transporters.

ATP Binding Cassette Transporter, Subfamily B↗

Organic and inorganic components in estuarine colloids: implications for sorption and transport of pollutants.

In colloids isolated from Chesapeake Bay and its subestuaries the concentrations of Al, Fe, and a number of trace elements were determined to vary with the clay mineral fraction that was most abundant in freshwater samples collected during the winter. The elements As, Ba, Sb, and Zn, however, increased with increasing organic content, indicating a covariance with the organic component. Organic analyses for amino acids (proteins), carbohydrates, and lipids indicate that these biopolymers comprised 4 to 22%, 20 to 60%, and less than 1%, respectively, of the colloidal organic carbon in these samples. The results are significant because amino acids and carbohydrates contain oxygen, nitrogen, and sulfur functional groups capable of reacting with trace metals and organic pollutants. The sorption properties of several neutral hydrophobic organic compounds, including PAHs and herbicides, and several aromatic amines were investigated using the estuarine colloidal material. The effects of several environmental variables on these sorption properties were determined. The results indicate that colloids have the capacity to sorb and transport relatively insoluble pollutants that otherwise might remain immobile in the environment. Colloidal organic matter in natural water systems (lakes, rivers, estuaries and the oceans, as well as groundwater) may serve as substrates for the sorption or binding of organic contaminants. Although most of the data has been developed using neutral hydrophobic organic compounds, data also exist for selected polar compound groups such as aromatic amines. The chemical behavior of these compound groups in interaction with DOM appears to have some similarity to their chemical interaction with sediments and soils. Partitioning constants are linear, except for polar compounds, and appear to be closely correlated to fundamental compound properties such as solubilities and octanol-water partition coefficients. Even though a variety of methods were used to collect the colloids for study and to determine partition coefficients, no single method appears to be superior. Ultrafiltration techniques appear to be optimal for collecting the colloids, since this method subjects the materials to less extreme chemical conditions than the preparation of humic extracts, whereas equilibrium techniques such as dialysis and head space analysis appear to yield the best results for partitioning constants. However, each of these techniques has limitations with respect to the classes of compounds that can be studied successfully.

Colloids↗

Difference in projections to the lateral and medial facial nucleus: anatomically separate pathways for rhythmical vibrissa movement in rats.

The present paper demonstrates that the lateral and medial subdivisions of the rat facial motor nucleus (NVII) receive differing mesencephalic and metencephalic projections. In order to study brain projections to facial nucleus, horseradish peroxidase (HRP) was injected iontophoretically into the entire facial nucleus or the following subdivisions: lateral, dorsolateral, medial, intermediate, and ventral. In the mesencephalic region, the retrorubral nucleus was found to project to the contralateral medial subdivision of NVII, while the red nucleus was found to project to the contralateral lateral subdivision of NVII. Other mesencephalic projections to the facial nucleus arose from the deep mesencephalic nucleus, oculomotor nucleus, central gray including interstitial nucleus of Cajal and nucleus Darkschewitsch, superior colliculus and substantia nigra (reticular). In the mesencephalic region, the Kölliker-Fuse nucleus, parabrachial nucleus, and the ventral nucleus of the lateral lemniscus projected mainly to the ipsilateral lateral subdivision of NVII. In addition, the trapezoid, pontine reticular, vestibular, and motor trigeminal nuclei were observed to have predominantly ipsilateral connections to the facial nucleus. In contrast, projections from the myelencephalic region were to both the lateral and medial subdivision of NVII. The medullary reticular nucleus, ambiguus nucleus, spinal trigeminal nucleus and parvocellular reticular nucleus projected to both lateral and medial subdivisions of NVII with an ipsilateral predominance. The gigantocellular and paragigantocellular reticular nuclei, raphe magnus, external cuneate nucleus and the nucleus of the solitary tract also projected to the facial motor nucleus. Surprisingly, no direct projections to the NVII were observed from diencephalic and telencephalic regions. Our findings that the lateral subdivision of NVII which innervates vibrissa-pad-muscles (Dom et al. 1973; Martin and Lodge 1977; Watson et al. 1982) receives different metencephalic and mesencephalic projections than medial subdivision which controls pinna movement (Henkel and Edwards 1978), suggest that the functional difference between these subdivisions is mediated by the anatomically separate pathways. We confirmed our anatomical findings by eliciting exclusively vibrissa responses by electrical stimulation of the nuclei which project to the lateral subdivision of NVII.

Afferent Pathways↗

Changes in human skeletal muscle contractile function following stimulated eccentric exercise.

Indices of human skeletal muscle contractile function were examined in nine subjects for up to 9 days following a single bout of stimulated eccentric exercise. Eccentric muscle actions of the knee extensor muscles were evoked by percutaneous electrical myostimulation (PES). Delayed onset muscle soreness (DOMS), elevated serum creatine kinase activity, chronic force loss, and a decline in the 20:100 Hz force ratio were observed in the days postexercise. The exercised knee extensor muscles demonstrated an impaired ability to respond to PES. This was evident by an increased time delay between the start of 100 Hz PES and the onset of contraction immediately postexercise [22.3 (SD 15.9)%, P < 0.01] and 3 days postexercise [14.9 (SD 18.1)%, P < 0.05]. Muscle relaxation rates appeared unaffected by the eccentric exercise protocol, where the muscles showed no differences in the time between the end of PES and the onset of relaxation (P > 0.05). During the days following the exercise, no significant differences were observed in the time between the start of contraction and attainment of 70% of the mean tetanic force following a single 1-s pulse of PES. Similarly, no significant differences were observed in the time between the start of relaxation and attainment of 70% of the total relaxation during the same time. The increased delay in excitation-contraction coupling observed immediately postexercise and 3 days after the exercise, may reflect a damage-induced delay in action potential propagation. Muscle relaxation rates postexercise remained unchanged, which would seem to indicate normal functioning of the sarcoplasmic reticulum, suggesting this was not the site of failure in excitation-contraction coupling.

Adult↗