Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injury.

Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission.

Transcriptional activation of the utrophin promoter B by a constitutively active Ets-transcription factor.

Duchenne muscular dystrophy is an X-linked genetic disease caused by the absence of functional dystrophin. Pharmacological upregulation of utrophin, the autosomal homologue of dystrophin, offers a potential therapeutic approach to treat Duchenne patients. Full-length utrophin mRNA is transcribed from two alternative promoters, called A and B. In contrast to the utrophin promoter A, little is known about the factors regulating the activity of the utrophin promoter B. Computer analysis of this second promoter revealed the presence of several conserved binding motives for Ets-transcription factors. Using electrotransfer of cDNA into mouse muscles, we demonstrate that a genetically modified beta-subunit of the Ets-transcription factor GA-binding protein potently activates a utrophin promoter B reporter construct in innervated muscle fibers in vivo. These results make the GA-binding protein and the signaling cascade regulating its activity in muscle cells, potential targets for the pharmacological modulation of utrophin expression in Duchenne patients.

Evaluation of the rabbit as a model for Chagas disease - II: histopathologic studies of the heart, digestive tract and skeletal muscle

In order to investigate the value of the rabbit as an experimental model for Chagas' disease, seventy one animals were inoculated with different Trypanosoma cruzi strains and routes. The rabbits were submitted to necropsy in acute (earlier than three months of infection), recent chronic (three to six months) and late chronic (later than six months) phases. Myocarditis, generally focal and endomysial, occurred in 94.1%, 66.7% and 70.8% of the infected rabbits respectively in the acute, recent chronic and late chronic phases. The myocardial inflammatory exudate was composed by mononuclear cells, and also polymorphonuclear cells in the acute phase. In most cases of the late chronic phase, the myocarditis was similar to that described in the indeterminate form of human chagasic patients. Initial fibrosis occurred in the three phases but was more severe and frequent in the early chronic. Advanced fibrosis occurred only in the late chronic phase. Tissue parasites occurred only in the acute phase. The digestive tract and skeletal muscles showed mild and occasional lesions. Our data indicate that experimentally infected chagasic rabbits repeat some lesions similar to that of humans chagasic patients, specially that of the indeterminate form. So, it may be a useful, however not an ideal, model.

Expression of substance P and preprotachykinin mRNA by primary sensory neurons in culture: regulation by factors present in peripheral and central target tissues.

Primary sensory neurons display various neuronal phenotypes which may be influenced by factors present in central or peripheral targets. In the case of DRG cells expressing substance P (SP), the influence of peripheral or central targets was tested on the neuronal expression of this neuropeptide. DRG cells were cultured from chick embryo at E6 or E10 (before or after establishment of functional connections with targets). Preprotachykinin mRNA was visualized in DRG cell cultures by either Northern blot or in situ hybridization using an antisense labeled riboprobe, while the neuropeptide SP was detected by immunostaining with a monoclonal antibody. In DRG cell cultures from E10, only 60% of neurons expressed SP. In contrast, DRG cell cultures performed at E6 showed a significant hybridization signal and SP-like immunoreactivity in virtually all the neurons (98%). The addition of extracts from muscle, skin, brain or spinal cord to DRG cells cultured at E6 reduced by 20% the percentage of neurons which express preprotachykinin mRNA and SP-like immunoreactivity. Our results indicate that factors issued from targets inhibit SP-expression by a subset of primary sensory neurons and act on the transcriptional control of preprotachykinin gene.

Histopathological study of experimental and natural infections by Trypanosoma cruzi in Didelphis marsupialis

Didelphis marsupialis, the most important sylvatic reservoir of Trypanosoma cruzi, can also maintain in their anal scent glands the multiplicative forms only described in the intestinal tract of triatomine bugs. A study of 21 experimentally and 10 naturally infected opossums with T. cruzi was undertaken in order to establish the histopathological pattern under different conditions. Our results showed that the inflammation was predominantly lymphomacrophagic and more severe in the naturally infected animals but never as intense as those described in Chagas' disease or in other animal models. The parasitism in both groups was always mild with very scarce amastigote nests in the tissues. In the experimentally infected animals, the inflammation was directly related to the presence of amastigotes nests. Four 24 days-old animals, still in embryonic stage, showed multiple amastigotes nests and moderate inflammatory reactions, but even so they survived longer and presented less severe lesions than experimentally infected adult mice. Parasites were found in smooth, cardiac and/or predominantly striated muscles, as well as in nerve cells. Differing from the experimentally infected opossums parasitism in the naturally infected animals predominated in the heart, esophagus and stomach. Parasitism of the scent glands did not affect the histopathological pattern observed in extraglandular tissues.

Physiological differences between cycling and running: lessons from triathletes

The purpose of this review was to provide a synopsis of the literature concerning the physiological differences between cycling and running. By comparing physiological variables such as maximal oxygen consumption (V O(2max)), anaerobic threshold (AT), heart rate, economy or delta efficiency measured in cycling and running in triathletes, runners or cyclists, this review aims to identify the effects of exercise modality on the underlying mechanisms (ventilatory responses, blood flow, muscle oxidative capacity, peripheral innervation and neuromuscular fatigue) of adaptation. The majority of studies indicate that runners achieve a higher V O(2max) on treadmill whereas cyclists can achieve a V O(2max) value in cycle ergometry similar to that in treadmill running. Hence, V O(2max) is specific to the exercise modality. In addition, the muscles adapt specifically to a given exercise task over a period of time, resulting in an improvement in submaximal physiological variables such as the ventilatory threshold, in some cases without a change in V O(2max). However, this effect is probably larger in cycling than in running. At the same time, skill influencing motor unit recruitment patterns is an important influence on the anaerobic threshold in cycling. Furthermore, it is likely that there is more physiological training transfer from running to cycling than vice versa. In triathletes, there is generally no difference in V O(2max) measured in cycle ergometry and treadmill running. The data concerning the anaerobic threshold in cycling and running in triathletes are conflicting. This is likely to be due to a combination of actual training load and prior training history in each discipline. The mechanisms surrounding the differences in the AT together with V O(2max) in cycling and running are not largely understood but are probably due to the relative adaptation of cardiac output influencing V O(2max) and also the recruitment of muscle mass in combination with the oxidative capacity of this mass influencing the AT. Several other physiological differences between cycling and running are addressed: heart rate is different between the two activities both for maximal and submaximal intensities. The delta efficiency is higher in running. Ventilation is more impaired in cycling than in running. It has also been shown that pedalling cadence affects the metabolic responses during cycling but also during a subsequent running bout. However, the optimal cadence is still debated. Central fatigue and decrease in maximal strength are more important after prolonged exercise in running than in cycling.

Patient-ventilator asynchrony during noninvasive ventilation: a bench and clinical study.

BACKGROUND: Different kinds of ventilators are available to perform noninvasive ventilation (NIV) in ICUs. Which type allows the best patient-ventilator synchrony is unknown. The objective was to compare patient-ventilator synchrony during NIV between ICU, transport-both with and without the NIV algorithm engaged-and dedicated NIV ventilators. METHODS: First, a bench model simulating spontaneous breathing efforts was used to assess the respective impact of inspiratory and expiratory leaks on cycling and triggering functions in 19 ventilators. Second, a clinical study evaluated the incidence of patient-ventilator asynchronies in 15 patients during three randomized, consecutive, 20-min periods of NIV using an ICU ventilator with and without its NIV algorithm engaged and a dedicated NIV ventilator. Patient-ventilator asynchrony was assessed using flow, airway pressure, and respiratory muscles surface electromyogram recordings. RESULTS: On the bench, frequent auto-triggering and delayed cycling occurred in the presence of leaks using ICU and transport ventilators. NIV algorithms unevenly minimized these asynchronies, whereas no asynchrony was observed with the dedicated NIV ventilators in all except one. These results were reproduced during the clinical study: The asynchrony index was significantly lower with a dedicated NIV ventilator than with ICU ventilators without or with their NIV algorithm engaged (0.5% [0.4%-1.2%] vs 3.7% [1.4%-10.3%] and 2.0% [1.5%-6.6%], P < .01), especially because of less auto-triggering. CONCLUSIONS: Dedicated NIV ventilators allow better patient-ventilator synchrony than ICU and transport ventilators, even with their NIV algorithm. However, the NIV algorithm improves, at least slightly and with a wide variation among ventilators, triggering and/or cycling off synchronization.

Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon.

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time  = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (-13±17% and -10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (-24±13% and -26±19%, P<0.01) with alteration of the central activation ratio (-24±24% and -28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: -18±18% and PF: -20±15%, P<0.01) and peak twitch (KE: -33±12%, P<0.001 and PF: -19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·(1)), lactate dehydrogenase (1145±511 UI·L(-1)), C-Reactive Protein (13.1±7.5 mg·L(-1)) and myoglobin (449.3±338.2 µg·L(-1)) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half.

Comparison between Two Methods for Diagnosis of Trichinellosis: Trichinoscopy and Artificial Digestion

Two direct methods for the diagnosis of trichinellosis were compared: trichinoscopy and artificial digestion. Muscles from 17 wistar rats, orally infected with 500 Trichinella spiralis encysted larvae were examined. From each of the following muscles: diaphragm, tongue, masseters, intercostals, triceps brachialis and cuadriceps femoralis, 648,440 larvae from 1 g samples were recovered. The linear correlation between trichinoscopy and artificial digestion was very high and significant (r=0.94, p< 0.0001), showing that both methods for the detection of muscular larvae did not differ significantly. In both methods, significant differences were found in the distribution of larvae per gramme of muscle

Anatomic shoulder arthroplasty: consequences of humeral head malposition

Purpose Third generation anatomic total shoulder prostheses offer a wide range of adaptability (size, thickness, retroversion and offset of the humeral head, cervico-diaphyseal angle) in order to reproduce anatomy and biomechanics of the shoulder as normal as possible. The large variability of the implants may also induce malposition. Our goal was to analyse the consequences of a humeral head malposition, which is one of the most frequent placement errors. Material and Methods A 3D finite element model of the glenohumeral joint, including the rotator cuff muscles and the deltoid, was used with the Aequalis anatomic prosthesis. Active abduction was simulated. Three humeral head placements were compared : anatomic positioning (A), 5 mm inferior positioning (B), 5 mm superior positioning (C). The effect of humeral head malposition was evaluated through the following quantities : the range of motion free of impingements, the glenohumeral contact pattern, and the stress within the polyethylene and the cement. Results Inferior positioning (B) of the humeral head produced a superior impingement before 90° of abduction, an inferior eccentric contact point on the glenoid, and 165% increase of cement stress. Superior positioning (C) of the humeral head produced a postero-superior eccentric contact point on the glenoid, 300% increase of glenohumeral contact pressure, 450% increase of polyethylene stress, and 207% increase of cement stress. Conclusion Malposition of the humeral head of anatomic prostheses induces biomechanical consequences that may preclude the glenoid survival. Particular attention must be paid to reproduce the humeral anatomy as normal as possible.

Familial aplasia of the trapezius muscle: clinical and MRI findings.

A 5-year-old boy was referred to our neurology clinic for suspected myopathy. His parents reported normal upper extremity strength and no limitation in daily activities; however, he was unable to raise his arms above his head. On examination, both shoulders were down-slanting and anteriorly displaced, leading to a webbed neck appearance. Muscle MRI demonstrated isolated bilateral aplasia of the trapezius muscles. His father was found to have a unilateral partial trapezius hypoplasia with no functional consequences. Conclusion:  Congenital aplasia of the trapezius muscle is a rare condition; bilateral aplasia of the muscle, having been reported in only five cases, is most often associated with aplasia of the pectoralis major. This is the first report to our knowledge to demonstrate bilateral isolated trapezius aplasia by MRI.

Patient satisfaction after biofeedback for constipation and pelvic floor dyssynergia.

Patients referred for chronic constipation frequently report symptoms of straining, feeling of incomplete evacuation, or the need to facilitate defecation digitally (dyschezia). When such patients show manometric evidence of inappropriate contraction or failure to relax the pelvic floor muscles during attempts to defecate, they are diagnosed as having pelvic floor dyssynergia (Rome I). To evaluate long-term satisfaction of patients with pelvic floor dyssynergia after biofeedback. Forty-one consecutive patients referred for chronic constipation at an outpatient gastrointestinal unit and diagnosed as having pelvic floor dyssynergia who completed a full course of biofeedback. Data have been collected using a standardised questionnaire. A questionnaire survey of patients' satisfaction rate and requirement of aperients was undertaken. Mean age and symptom duration were respectively 41 and 20 years. Half of patients reported fewer than 3 bowel motions per week. Patients were treated with a mean of 5 biofeedback sessions. At the end of the therapy pelvic floor dyssynergia was alleviated in 85% of patients and 49% were able to stop all aperients. Satisfaction was maintained at follow-up telephone interviews undertaken after a mean period of 2 years, as biofeedback was helpful for 79% of patients and 47% still abstained from intake of aperients. Satisfaction after biofeedback is high for patients referred for chronic constipation and diagnosed with pelvic floor dyssynergia. Biofeedback improves symptoms related to dyschezia and reduces use of aperients.

Etude du réveil printanier chez les fourmis des bois (groupe Formica rufa) dans le Jura vaudois (Suisse)

Les auteurs ont étudié les différentes étapes du réveil printanier chez deux espèces du groupe Formica rufa dans le Jura vaudois. Les variables considérées ont été la température externe et les températures à l'intérieur de la fourmilière à des profondeurs variables. Le processus du réveil printanier est fortement dépendant des conditions météorologiques. Il dure en moyenne 6 semaines (mi-avril- fin mai). L'apparition des reines à la surface a permis de mettre en évidence les points suivants: - 3 à 30% des reines ne sont pas fécondées (moyenne 16 %) - 90% environ des reines récoltées en surface possèdent des ovocytes matures, qu'elles soient fécondées ou non ainsi que des muscles alaires intacts. Les auteurs formulent l'hypothèse que seules les reines âgées de moins d'une année viennent à la surface.

Patient-ventilator asynchrony during non-invasive ventilation for acute respiratory failure: a multicenter study.

OBJECTIVE : To determine the prevalence of patient-ventilator asynchrony in patients receiving non-invasive ventilation (NIV) for acute respiratory failure. DESIGN : Prospective multicenter observation study. SETTING : Intensive care units in three university hospitals. METHODS: Patients consecutively admitted to ICU were included. NIV, performed with an ICU ventilator, was set by the clinician. Airway pressure, flow, and surface diaphragmatic electromyography were recorded continuously for 30 min. Asynchrony events and the asynchrony index (AI) were determined from visual inspection of the recordings and clinical observation. RESULTS: A total of 60 patients were included, 55% of whom were hypercapnic. Auto-triggering was present in 8 (13%) patients, double triggering in 9 (15%), ineffective breaths in 8 (13%), premature cycling 7 (12%) and late cycling in 14 (23%). An AI > 10%, indicating severe asynchrony, was present in 26 patients (43%), whose median (25-75 IQR) AI was 26 (15-54%). A significant correlation was found between the magnitude of leaks and the number of ineffective breaths and severity of delayed cycling. Multivariate analysis indicated that the level of pressure support and the magnitude of leaks were weakly, albeit significantly, associated with an AI > 10%. Patient comfort scale was higher in pts with an AI < 10%. CONCLUSION: Patient-ventilator asynchrony is common in patients receiving NIV for acute respiratory failure. Our results suggest that leaks play a major role in generating patient-ventilator asynchrony and discomfort, and point the way to further research to determine if ventilator functions designed to cope with leaks can reduce asynchrony in the clinical setting.

Respiratory muscle training enhances maximal minute ventilation and forced vital capacity in adolescent athletes.

Introduction. Respiratory difficulties in athletes are common, especially in adolescents, even in the absence of exercise-induced bronchoconstriction. Immaturity of the respiratory muscles coupling at high respiratory rates could be a potential mechanism. Whether respiratory muscle training (RMT) can positively influence it is yet unknown. Goal. We investigate the effects of RMT on ventilation and performance parameters in adolescent athletes and hypothesize that RMT will enhance respiratory capacity. Methods. 12 healthy subjects (8 male, 4 female, 17±0.5 years) from a sports/study high school class, competitively involved in various sports (minimum of 10 hours per week) underwent respiratory function testing, maximal minute ventilation (MMV) measurements and a maximal treadmill incremental test with VO2max and ventilatory thresholds (VT1 and VT2) determination. They then underwent one month of RMT (4 times/week) using a eucapnic hyperventilation device, with an incremental training program. The same tests were repeated after RMT. Results. Subjects completed 14.8 sessions of RMT, with an increase in total ventilation per session of 211±29% during training. Borg scale evaluation of the RMT session was unchanged or reduced in all subjects, despite an increase in total respiratory work. No changes (p>0.05) were observed pre/post RMT in VO2max (53.4±7.5 vs 51.6±7.7 ml/kg/min), VT2 (14.4±1.4 vs 14.0±1.1 km/h) or Speed max at end of test (16.1±1.7 vs 15.8±1.7 km/h). MVV increased by 9.2% (176.7±36.9 vs 192.9±32.6 l/min, p<0.001) and FVC by 3.3% (6.70±0.75 vs 4.85±0.76 litres, p<0.05). Subjective evaluation of respiratory sensations during exercise and daily living were also improved. Conclusions. RMT improves MMV and FVC in adolescent athletes, along with important subjective respiratory benefits, although no changes are seen in treadmill maximal performance tests and VO2max measurements. RMT can be easily performed in adolescent without side effects, with a potential for improvement in training capacity and overall well-being.