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In vivo effects of tumor necrosis factor-alpha on capillary permeability and vascular tone in a skeletal muscle.

BACKGROUND: The present study aims at analysing short-term effects of TNF alpha on capillary permeability, on transcapillary fluid fluxes, and on vascular tone in a whole organ cat skeletal muscle in vivo preparation. METHODS: The denervated muscle was isolated from the body but with intact vascular supply. The experimental setup allowed continuous recording of vascular tone, of hydrostatic capillary pressure and tissue volume variations. The capillary filtration coefficient (CFC), which represents the net effect for transcapillary fluid exchange of capillary permeability and number of open capillaries, was calculated before and during intra-arterial TNF infusion. RESULTS: We found that TNF had a minor effect on vascular tone in terms of a small vasodilation, and that no effect on hydrostatic capillary pressure could be recorded. CFC increased by 64% during the TNF infusion and this increase must be attributed to an increase in capillary permeability rather than an increase in the number of capillaries available for fluid exchange since the TNF effect on vascular tone is small. This was also supported by TNF-induced transcapillary filtration. CONCLUSIONS: TNF is a potent drug for increasing capillary permeability causing transcapillary filtration in vivo. Its release, e.g. during sepsis, may therefore contribute to the capillary leakage often seen in this clinical situation.

Animals↗

Value of electromyography in differential diagnosis of laryngeal joint injuries after intubation.

Laryngeal joint injury or arytenoid dislocation is not an uncommon complication resulting from intubation trauma, and is best evaluated by laryngeal electromyography (EMG) combined with laryngoscopic examinations. Two cases of cricoarytenoid joint injuries after intubation are reported along with laryngeal EMG findings. Early diagnosis of arytenoid dislocation is important for appropriate surgical management and better prognosis. However, the reported cases, because of delayed referrals, showed prolonged cricoarytenoid joint injuries associated with thyroarytenoid muscle denervation or myopathy, and resultant vocal fold immobility. The results of laryngeal EMG in cricoarytenoid joint injuries can be classified into three different patterns: 1) normal recruitment, 2) myopathy, and 3) denervation or reinnervation of the thyroarytenoid muscles. It is particularly valuable to sample different portions of the thyroarytenoid muscles with EMG in order to evaluate different patterns or pathologic changes of the muscles and nerve paralysis.

Adult↗

Intestinal giardiasis, steatorrhoea and peripheral nerve dysfunction.

Two patients presented with similar peripheral neuropathic symptoms. Muscle denervation was shown by electromyography and muscle biopsy. Motor and sensory nerve conduction studies were normal. Both patients had intestinal giardiasis: 1 had asymptomatic steatorrhoea, and the other had diarrhoea and abdominal pain. Treatment with metronidazole abolished the gastrointestinal symptoms. After a delay of several months the neurological symptoms also gradually improved. No other cause of peripheral neuropathy was apparent on investigation, and the relationship between the intestinal giardiasis and the peripheral neuropathy is discussed.

Adult↗

Results of the modified Hartl gracilis plasty.

Follow-up results of patients who had a gracilis plasty for incontinence after rectal atresia showed that in 8 of 11 patients there was marked improvement. 6 children had good continence and 3 sufficient continence. Similar results have been reported by others and are encouraging. The high percentage of infected wounds did not seem to influence the results. The results in operations for incontinence with myelomeningoceles were different. Only 5 times was there sufficient continence and in only 2 patients was subjective improvement recorded. It must be pointed out that the function of the gracilis muscle was tested preoperatively by electromyographic examination. These unsatisfactory results can undoubtedly also be achieved with conservative therapy. Incontinence with myelomeningoceles is therefore no indication for a gracilis plasty. These varying results appear to indicate that success can only be obtained with a gracilis plasty if there are still functioning parts of the pelvic musculature present and if parts of the anorectum are able to mature. If this is true, then there is a direct connection between the results we obtained and those achieved by free muscle transplantation or transposition of a denervated muscle. No doubt, the gracilis plasty is not the only available method to achieve continence, but it will often improve the function of the sphincter in patients with incontinence following rectal atresia operations.

Adolescent↗

Coadministration of interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease.

Interleukin-6 (IL-6), a multipotential cytokine, initiates signal transduction pathways similar to those of ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF). These molecules share the signal transducing receptor component, gp130. IL-6 triggers homodimerization of gp130, whereas CNTF and LIF induce heterodimerization of gp130 and LIF receptor. Although CNTF or LIF treatment attenuates motor deficits in wobbler mouse motor neuron disease (MND), neuroprotective effects of IL-6 on this animal have not yet been clarified. Here we studied whether simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) can ameliorate symptomatic and neuropathological changes in wobbler mouse MND. After clinical diagnosis at postnatal age 3-4 weeks, wobbler mice received subcutaneous injection with human recombinant IL-6 (1.0 mg/kg), human sIL-6R (0.5 mg/kg), IL-6 + sIL-6R or vehicle, daily for 4 weeks in a blind fashion. Compared to vehicle, coadministration with IL-6 and sIL-6R potentiated grip strength, attenuated muscle contractures in the forelimbs, reduced denervation muscle atrophy and prevented degeneration of spinal motor neurons. Single administration with IL-6 or sIL-6R did not retard the symptomatic and neuropathological progression, although IL-6-treated mice did not raise anti-IL-6 antibodies. Treatment with IL-6 + sIL-6R, but not with IL-6 or sIL-6R alone delayed progression of wobbler mouse MND. Our results indicate that the neuroprotective mechanism for IL-6/sIL-6R on wobbler mouse MND differs from that of CNTF or LIF alone. We hypothesize that IL-6/sIL-6R complex may function on motor neurons through activation and homodimerization of gp130.

Animals↗

Recovery potential of muscle after partial denervation: a comparison between rats and humans.

The response to partial denervation is compared for the tibialis anterior muscle in the rat and the thenar muscle group in the human. Partial denervation in the human was a result of spinal cord injury, while partial denervation in the rat was induced by sectioning of the L4 ventral root. In some animals, a spinal cord transection at the T12-13 level was also performed to determine whether spinal cord injury affected the sprouting capability of motoneurons caudal to the injury site. Motor units were isolated by intramuscular microstimulation in the human and by ventral root splitting in a terminal experiment in the rat. Motor unit numbers were estimated by dividing the amplitude of the electromyogram (EMG) and the peak twitch force in response to maximum stimulation of the muscle nerve by the average unit EMG and twitch force, respectively. In both the rat and the human, surviving motor units enlarged as a function of the degree of partial denervation. Moreover, all surviving motor units appeared to enlarge proportionately. The limit to sprouting was tested systematically in the rat. On average, single motor units enlarged up to about five times their original size, resulting in the ability to compensate for up to 80% of motoneuron loss. The reason for this limit remains unclear, but histological data suggest that sprouting may be confined to the more distal regions of the motor axon, such that reinnervation of denervated muscle fibers is confined to the territory of the original motor unit.

Animals↗

Neurotrophic control of skeletal muscle phospholipids.

The phospholipid composition of rat gastrocnemius muscles was assessed one to nine days after sciatic nerve transection was performed either close to the muscle (5-8 mm from the point of entrance of the nerve into the muscle for short-stump nerve sections) or far from it (30-35 mm central to the nerve's point of entrance for long-stump nerve sections). In both instances, denervation did not cause striking changes in total phospholipid content but resulted in a selective loss of 1,2-diacyl-sn-glycero-3-phosphorylethanolamine (phosphatidyl ethanolamine, GPE). The quantity of GPE in denervated muscles was found to be significantly less than that it controls (p less than 0.01) within one day for short-stump preparations, as compared to three days for long-stump preparations. Also, direct comparison of short- and long-stump GPE values showed significant differences (p less than 0.01) at all times from the first to the fifth day following denervation, with no difference detected thereafter. These results imply that maintenance of skeletal muscle GPE involves a neurogenic influence which is independent of nerve-evoked muscle activity. This conclusion may help us understand neuromuscular diseases in which perturbation of phospholipid components has been implicated.

Animals↗

Satellite cells on isolated myofibers from normal and denervated adult rat muscle.

Satellite cells (SCs) in normal adult muscle are quiescent. They can enter the mitotic program when stimulated with growth factors such as basic FGF. Short-term denervation stimulates SC to enter the mitotic cycle in vivo, whereas long-term denervation depletes the SC pool. The molecular basis for the neural influence on SCs has not been established. We studied the phenotype and the proliferative capacity of SCs from muscle that had been denervated before being cultured in vitro. The expression of PCNA, myogenin, and muscle (M)-cadherin in SCs of normal and denervated muscle fibers was examined at the single-cell level by immunolabeling in a culture system of isolated rat muscle fibers with attached SCs. Immediately after plating (Day 0), neither PCNA nor myogenin was present on normal muscle fibers, but we detected an average of 0.5 M-cadherin(+) SCs per muscle fiber. The number of these M-cadherin(+) cells (which are negative for PCNA and myogenin) increased over the time course examined. A larger fraction of cells negative for M-cadherin underwent mitosis and expressed PCNA, followed by myogenin. The kinetics of SCs from muscle fibers denervated for 4 days before culturing were similar to those of normal controls. Denervation from 1 to 32 weeks before plating, however, suppressed PCNA and myogenin expression almost completely. The fraction of M-cadherin(+) (PCNA(-)/myogenin(-)) SCs was decreased after 1 week of denervation, increased above normal after denervation for 4 or 8 weeks, and decreased again after denervation for 16 or 32 weeks. We suggest that the M-cadherin(+) cells are nondividing SCs because they co-express neither PCNA or myogenin, whereas the cells positive for PCNA or myogenin (and negative for M-cadherin) have entered the mitotic cycle. SCs from denervated muscle were different from normal controls when denervated for 1 week or longer. The effect of denervation on the phenotypic modulation of SCs includes resistance to recruitment into the mitotic cycle under the conditions studied here and a robust extension of the nonproliferative compartment. These characteristics of SCs deprived of neural influence may account for the failure of denervated muscle to fully regenerate. (J Histochem Cytochem 47:1375-1383, 1999)

Animals↗

Denervation enhances spontaneous inflammatory myopathy in SJL mice.

We studied the effect of denervation on the spontaneous inflammatory myopathy that occurs in SJL mice. Cryosections from innervated and denervated calf muscles were assessed for severity of inflammation, relative proportions of mononuclear cell subsets, and major histocompatibility complex (MHC) class I expression. A significant increase in mononuclear cell infiltrates occurred in the denervated muscle. Denervation also changed the composition of mononuclear cell infiltrates towards a higher percentage of CD8(+) T cells (19% versus 11%). MHC class I expression was enhanced in denervated muscle compared with innervated muscle. Our findings indicate that inflammation in muscle may be enhanced by denervation.

Animals↗

The use of botulinum toxin type A in aesthetic mandibular contouring.

The lower third of Asian faces is wider than that of Caucasians and it is determined by the size and width of the mandibular bone and the thickness of muscles and subcutaneous fat tissues surrounding it. Efforts to create an aesthetically slim and smooth facial contour line in nonobese people have led the authors to focus on two approaches: surgical resection of the masseteric muscle and modeling ostectomy of the square-angled mandibular bone. Because these procedures present some problems, the authors adopted a nonsurgical concept that chemically denervates muscles and reduces the bulk of the muscle. The authors have conducted a total of 1021 clinical cases from March of 2001 through September of 2002, in which patients were treated with botulinum toxin type A (Dysport; Ipsen Ltd, Slough, United Kingdom) for remodeling the lower facial contour line; 383 of those cases were followed up for at least 3 months after the initial injection. A database was made by measuring the change in the thickness of the injected muscle with an ultrasonogram. Eleven patients underwent resection of the mandibular angle before injection. The preinjection ostectomy group was involved in the study as a result of their dissatisfaction with the surgical results; they had a rather thick masseter muscle and not a bone problem. Some had both bone problems and a thick masseter muscle. Three months after the botulinum toxin injection, the thickness of the muscle was reduced by 31 percent on average. The atrophic effect of injection was observed after 2 to 4 weeks for most patients. Seventy percent of the 383 patients tracked were greatly satisfied with the result, with another 23 percent generally satisfied. No long-term side effects were reported. Masseteric hypertrophy is frequent in Asians because of racial characteristics and dietary habits. Botulinum toxin type A has made a new epoch in facial contouring for Asians. Considering that Asians have a prominent malar and a prominent mandible angle, the reduction in the thickness of the masseter can provoke relative prominence of the malar and mandible angle. Therefore, precise indication and anatomy of the facial muscle should be thoroughly understood, which will decrease the incidence of side effects and problems. Botulinum toxin type A (Dysport) injection is simple in technique, has few side effects, and promises a rapid return to daily life. The authors conclude that the injection of botulinum toxin type A can replace surgical masseter resection.

Adult↗

[The plasticity of motor units in change of the activity pattern by electric stimulation--electrostimulation and its possible clinical applications].

Motoneuron and muscle fibers interact on the motor unit level, whereby discharge characteristics from the neuron imposed on the muscle seem to play a major role. Within the unit all muscle fibers are biochemically homogeneous and display a high degree of plasticity under different functional demands. To distinguish the existing different units rationals are listed that classify the units by physiological and histochemical parameters. Furthermore the review summarizes the available knowledge on the importance of activity patterns--as a biological principle--involved in the control of phenotypic expression of innervated and denervated muscle. The sequelae are shown of electrical stimulation on innervated and denervated animal muscles. In extent to these findings the consequences are discussed for stimulation procedures that can be imposed on normal and diseased human muscles as a therapeutic tool.

Electric Stimulation Therapy↗

Histochemistry and acetylcholine receptor distribution in normal and denervated monkey extraocular muscles.

In monkey extraocular muscles (EOM), a battery of histochemical reactions delineates three muscle fiber types, coarse, fine, and granular. Normal EOM are compared with EOM denervated by intracranial oculomotor nerve section. The experimentally denervated EOM fibers did not show the constellation of histologic responses typical of denervated limb muscle, making a diagnosis of a denervation process in EOM muscle very difficult. Although the denervated fine and granular fibers (but not the coarse fibers) develop diffuse extrajunctional acetylcholine receptors (AChR) following experimental denervation, this is not a reliable criterion of denervation because not all of those fibers developed it and they did not show it beyond a 12-week period following nerve section; moreover, myopathic mechanisms have previously been shown capable of provoking diffuse extrajunctional AChR in limb-muscle fibers.

Acetylcholine↗

Clenbuterol treatment stimulates cell proliferation in denervated chick gastrocnemius muscle.

Daily administration of clenbuterol, a beta adrenoceptor agonist (0.5 mg/kg body weight; for 7 days) to normal innervated and denervated adult chicks (Gallus domesticus) resulted in different growth related responses by gastrocnemius muscle. While normal innervated muscle undergoes hypertrophy, structural reorganization in denervated tissue is accomplished by the de novo emergence of new cells. A contrasting cell population with extremely narrow cross sectional dimensions is a characteristic feature of denervated muscle in presence of clenbuterol. Measurement of fiber dimensions, number of cells per unit area and examination of histochemical preparations support this.

Adrenergic beta-Agonists↗

Simultaneous reconstruction of the Achilles tendon and soft-tissue defect using only a latissimus dorsi muscle free flap.

The combined loss of the Achilles tendon and the overlying soft tissue in the young ambulant patient with expectations of a normal life is a challenging problem. These patients need not only soft tissue but also dynamic and functional reconstruction. Four cases of major defects of the Achilles tendon and overlying soft tissue after trauma are presented. In each case, the tendon and the overlying soft tissues were reconstructed using only a latissimus dorsi muscle free flap and overlying split-thickness skin graft. In conventional methods, evolved in the reconstruction of the Achilles tendon and soft tissue, the size of the defect was a limit. However, this technique can be used to reconstruct an extensive defect, including distal calf muscle to the plantar metatarsal area. In one case, the flap was harvested in a myocutaneous unit, and the skin portion was deepithelialized for the coverage and enough padding on the bony exposure area in reverse position. The purpose of the present study was to reevaluate the potential of denervated muscle flap for a force-bearing conduit as an alternative reconstructive method of the Achilles tendon. The denervated latissimus dorsi muscle in this study eventually experienced the process of atrophy and fibrosis but maintained its original length. Although there remained some atrophic muscle fibers, a fibrosis of the muscle fibers formed a tendon-like fibrous band, and so the action of the posterior calf muscle could be transmitted through the tendon-like fibrotic change of the denervated latissimus dorsi muscle. The advantages of this technique are that (1) it is a single procedure, (2) it is adaptable to a wide range of defect sizes, (3) it allows faster wound healing supported by well-vascularized tissues, (4) it produces satisfactory function of the ankle joint and a padding effect, and (5) it produces good contour of the posterior calf to the sole and an acceptable donor-site morbidity.

Achilles Tendon↗

The expression of the myogenic regulatory factors in denervated and normal muscles of different phenotypes.

The nerve is known to play a pivotal role in the diversification of muscle fibre types postnatally. Reducing neuronal activity in a slow muscle such as the soleus by denervation, switches on genes associated with a fast muscle phenotype. On the other hand, denervating a fast muscle such as the extensor digitorum longus (EDL) induces the conversion of fast fibres to a 'slower' contractile phenotype. The myogenic regulatory factors (MRFs) are proposed as the regulators of muscle phenotype as MyoD and myogenin have been shown to differentially accumulate in fast and slow muscle upon the induction of fibre type transformation. The denervation model has been used in the present study to induce changes in MRF expression in the muscles of the lower hindlimb which have distinct phenotypic characteristics. The level of MRF expression in pairs of denervated and innervated soleus, EDL, tibialis anterior (TA), plantaris and gastrocnemius muscles has been determined by Northern analysis and compared. The present study has shown that each muscle responds differently to denervation with respect to the increases in MRF expression. Fast muscles responded very quickly to denervation by increasing the level of MRF transcripts while slow muscles did not show significant increases in expression after 48 h denervation. The innervated EDL (fast) and soleus (slow) muscle differed with respect to the level of MRF-4 expressed, MRF-4 being expressed at higher levels in the slow muscle compared to the fast, suggesting that MRF-4 is important in the maintenance of a slow muscle phenotype. Moreover, MRF-4 and myogenin show the greatest fold increases in expression in the fast muscles examined. MyoD and Myf 5 show less dramatic increase in expression in response to denervation but exhibit the greatest fold increases in the fast muscles compared to slow.

Animals↗

Changes in level of certain serum constituents following sciatectomy in the common frog, Rana tigrina (Daud).

Effect of unilateral (one leg) and bilateral (two legs) sciatectomy was studied on certain serum constituents in the male frog over a period of 3 weeks. The level of creatine kinase, acid and alkaline phosphatases, urea, glucose and proteins increased initially following sciatectomy and decreased subsequently from day 14 onwards, the per cent change being more pronounced in case of bilaterally sciatectomized frogs. The present results indicate an increase in the rate of deamination of proteins in the liver, an impairment in the transportation processes across the cell membrane and an increase in cellular lysosomal activity on sciatectomy suggesting a change either in the amount or in the rate of various enzyme reactions. It is concluded that sciatectomy induces alterations in general metabolic activities and the functional state of the animal. Altered values of various serum constituents thus permit to speculate analysis of the factor that may be contributing to the atrophic processes and the wasting of the muscle fibres known to set in the denervated muscle.

Animals↗