Fatigue during stretch-shortening cycle exercises: changes in mechanical performance of human skeletal muscle

Stretch-shortening cycle (SSC), which is a normal contraction behavior of muscle, was used as a model to investigate muscular fatigue. Nine male volunteers were subjected to 100 repeated and exhaustive SSC contractions of the forearm extensors using a special sledge apparatus incorporating a force plate system. The fatigue contractions were performed on submaximal levels but the before-after comparison also included maximal drop-jump condition on the sledge as well as falls on to the floor. The results indicated that in the 100 submaximal SSCs the fatigue was characterized by increases in the contact times for both the eccentric and concentric phases of SSC, but the influence was more pronounced on the concentric part. The force-time curves during contact on the platform were influenced by fatigue so that the initial force peak became higher and the subsequent initial drop of force more pronounced. During submaximal and maximal drops, the angular velocities changed in the two phases of SSC. With progressing fatigue, the eccentric maximal angular velocity increased and the corresponding concentric velocities decreased. These changes were accompanied by slight changes in the elbow joint mechanism with respect to the contact, release, and maximal flexion angles. The results suggest that repeated SSC induces fatigue and the fatigue effects on the mechanical behavior of the muscle are very much similar to those induced by either isometric or concentric fatigue contractions. However, the transfer of the energy between eccentric and concentric phases was drastically reduced and this implies that SSCs can be used effectively to examine the fatiguability of the system regulating muscle stiffness during exercise.     

Platelets as targets of snake venom metalloproteinases

For centuries snake venoms have been known to interfere with haemostasis and this is now known basically due either to toxins activating/inhibiting clotting factors, having effects on blood vessels or interfering with platelet function. In this short review, the interaction of one major group of toxins, the snake venom metalloproteinases, with platelets is considered. This is relevant for understanding the mechanism of haemorrhage induced by these toxins.     

Assessment of vector microfilarial uptake as a comparatively non-invasive technique for monitoring onchocerciasis treatment campaigns in the Americas

Summary Since 1992, efforts have been made to combat onchocerciasis in Guatemala through mass distribution of ivermectin. The impact of the campaign is assessed by taking skin-snips from sentinel groups within selected communities. This method gives an estimate of the prevalence and intensity of infection, and thus the efficacy of the treatment. In some communities people are becoming reluctant to volunteer for skin-snipping, and so there is a need for an alternative technique that will give quantitative results. In most hyperendemic communities in Guatemala, biting blackflies are so ubiquitous that few people object to allowing 10 to 20 flies to engorge upon them. We examined data on the quantitative uptake of microfilariae by Simulium ochraceum before and after ivermectin distribution to see whether results similar to skin-snip data could be obtained. Counts of microfilariae ingested by S. ochraceum are compared to the numbers found in skin-snips from the same volunteers. In a group of 31 untreated infected persons, a skin-snip survey detected 64.5% positive, while feeding flies (vector microfilarial uptake, VmfU) detected 96.8%. Post-treatment, in a sample of 58 of whom 52 (89.7%) had a history of infection, both skin-snips and VmfU detected 54.2%. Vector blood meals contained more microfilariae than a mg of skin before treatment, but both recorded about equal numbers after treatment. When the data set was subdivided to compare samples taken at 2–3, 6–8 and 14–17 months post-treatment, the effect of ivermectin was still apparent at 6–8 months, but had virtually disappeared by 14 months post-treatment. A surprising observation was that the flies ingested fewer microfilariae from treated persons than was expected from the skin densities as estimated by skin-snip. This effect lasted for over 8 months, and could indicate that ivermectin has a greater effect on transmission than previously suspected. We conclude that VmfU could be used as an alternative to skin-snipping, and discuss the ethical implications.     

Antibodies to the polymeric immunoglobulin receptor with different binding and trafficking patterns

The polymeric immunoglobulin receptor (pIgR) has been proposed as a therapeutic target, but its potential depends on the efficiency of uptake and trafficking of the receptor ligand. Mouse monoclonal antibodies (Mabs) directed against pIgR, selected for strong binding to secretory component (SC) and secretory IgA (sIgA), were tested in a transcytosis assay in 16HBEo--cells (human bronchial epithelial cell line) transfected with human pIgR. Intracellular trafficking was followed by confocal microscopy. Mabs fell into two classes. For two Mabs, transcytosis from basolateral to apical surface is rapid, unidirectional, and little Mab is retained in the cell. For three Mabs, basolateral to apical transcytosis occurs to a significantly lesser extent, reverse transcytosis is permitted, and some of the Mab is retained in the perinuclear region even after 24 h. When tested for their ability to recognize and immunoprecipitate pIgR with systematic truncations and deletions of the five immunoglobulin (Ig)-like domains, all Mabs bound to the fifth Ig-like domain, but three of them also bound to the C-terminal region of pIgR near the plasma membrane. Different binding sites probably account for the different trafficking of these Mabs and may predict differential therapeutic utility.     

Mechanical efficiency of pure positive and pure negative work with special reference to the work intensity

The mechanical efficiencies of pure positive (eta) and pure negative (eta-) work were investigated on a special "sledge ergometer" with 25 and 36 subjects, respectively. The work intensities varied in positive work between 40% and 90% and in negative work from 30% to 120% of the maximum concentric exercise. In 54 exercises of positive work, eta was 17.1% +/- 2.2%, and its value correlated negatively with the work intensity (r = 0.367, P less than 0.01) and with the average knee angular velocity, omega+ (r = 0.359, P less than 0.01). In 103 eccentric exercises, eta- was on the average 80.2% +/- 31.8%, correlating positively with the work intensity (r = 0.396, P less than 0.01). Both inter- and intrasubject variations were large (32%-163%). The integrated electrical activity (IEMG) of the leg extensor muscles increased with an increase of work intensity both in the positive and in the negative work situations. Less efficient MU recruitment in higher positive work rates is suggested to be the reason for the decrease in eta, whereas better stiffness regulation via increased preactivation is speculated to cause high values of eta- in higher work intensities in eccentric exercise.     

Blockade of NMDA receptors located at the dorsomedial prefrontal cortex impairs spatial working memory in rats

We investigated the effects of NMDA and muscarinic acetylcholine receptor blockade in the rostral part of dorsomedial (dmPFC) and dorsolateral prefrontal cortex (dlPFC) on spatial working memory (SWM) (delayed non-matching to position task (DNMTP)). The NMDA antagonist, CPP (0.01, 0.03, 0.1 and 0.3 microg/hemisphere) and the muscarinic antagonist, scopolamine (10 microg/hemisphere) were locally infused into the brain of male Wistar rats. In the mPFC CPP 0.1 microg disrupted SWM delay-dependently and CPP 0.3 microg caused a delay-independent performance deficit. Scopolamine disrupted non-cognitive performance, but did not affect SWM accuracy. In the dlPFC, scopolamine or lower doses of CPP did not affect SWM accuracy, but CPP 0.3 microg disrupted non-cognitive performance. We concluded that the NMDA receptors in the dmPFC regulate SWM processes, whereas the muscarinic receptors in the dmPFC mediate non-cognitive performance in the DNMTP task.     

Additional Diagnostic Yield of Adding Serology to PCR in Diagnosing Viral Acute Respiratory Infections in Kenyan Patients 5 Years of Age and Older

The role of serology in the setting of PCR-based diagnosis of acute respiratory infections (ARIs) is unclear. We found that acute- and convalescent-phase paired-sample serologic testing increased the diagnostic yield of naso/oropharyngeal swabs for influenza virus, respiratory syncytial virus (RSV), human metapneumovirus, adenovirus, and parainfluenza viruses beyond PCR by 0.4% to 10.7%. Although still limited for clinical use, serology, along with PCR, can maximize etiologic diagnosis in epidemiologic studies.     

Risk factors for active trachoma and Chlamydia trachomatis infection in rural Ethiopia after mass treatment with azithromycin

Objectives To investigate risk factors for ocular Chlamydia trachomatis infection and active trachoma, comparing communities receiving or not receiving an intervention programme of community‐wide azithromycin treatment and health education. Methods In a 3‐year post‐intervention follow‐up survey, 1722 children aged 3–9 years, from randomly selected households in 37 communities, were examined for signs of active trachoma and had samples taken to test for ocular C. trachomatis by polymerase chain reaction. Multivariate random effects logistic regression analyses considered interventions at community level, adjusting for other independent risk factors as appropriate. Results Younger age, ocular discharge and flies on eyes were risk factors for active trachoma in communities with and without antibiotic treatment. After azithromycin treatment, odds of active trachoma were lower in children aged 6–9 years than in children aged 3–5 years (OR 0.48, 95% CI: 0.36–0.66) and higher for children with ocular discharge (OR 4.5, 95% CI: 2.6–7.7) or flies on their eyes (OR 2.5, 95% CI: 1.6–3.7). Odds of C. trachomatis infection were lower in children aged 6–9 years than in younger children (OR 0.47, 95% CI: 0.23–0.96); and in children who received 2 or 3 doses rather than 1 (OR 0.26, 95% CI: 0.08–0.88). Conclusions In communities that received or did not receive the mass antibiotic treatment, the same risk factors for C. trachomatis and active trachoma were identified. Education and environmental improvements need to supplement antibiotic campaigns in order to positively impact on these remaining child level risk factors.     

Adaptive reconfiguration of the human NK‐cell compartment in response to cytomegalovirus: A different perspective of the host‐pathogen interaction

As discussed in this review, human cytomegalovirus (HCMV) infection in healthy individuals is associated with a variable and persistent increase of NK cells expressing the CD94/NKG2C activating receptor. The expansion of NKG2C⁺ NK cells reported in other infectious diseases is systematically associated with HCMV co‐infection. The functionally mature NKG2C^bright NK‐cell subset expanding in HCMV⁺ individuals displays inhibitory Ig‐like receptors (KIR and LILRB1) specific for self HLA class I, and low levels of NKp46 and NKp30 activating receptors. Such reconfiguration of the NK‐cell compartment appears particularly marked in immunocompromised patients and in children with symptomatic congenital infection, thus suggesting that its magnitude may be inversely related with the efficiency of the T‐cell‐mediated response. This effect of HCMV infection is reminiscent of the pattern of response of murine Ly49H⁺ NK cells against murine CMV (MCMV), and it has been hypothesized that a cognate interaction of the CD94/NKG2C receptor with HCMV‐infected cells may drive the expansion of the corresponding NK‐cell subset. Yet, the precise role of NKG2C⁺ cells in the control of HCMV infection, the molecular mechanisms underlying the NK‐cell compartment redistribution, as well as its putative influence in the response to other pathogens and tumors remain open issues.