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Proportions of slow-twitch and fast-twitch extrafusal fibers in receptive fields of tendon organs in chicken leg muscles.

Golgi tendon organs are mechanoreceptors that monitor the contractile force produced by motor units. Receptors are most responsive to contractions of extrafusal muscle fibers that terminate closest to them and on them. Three anterior and four posterior chicken leg muscles were examined. Proportions of immunohistochemically identified slow-twitch extrafusal fibers and fast-twitch extrafusal fibers were calculated for 374 tendon organ receptive fields. Tendon organs were observed in muscle regions occupied either by slow-twitch fibers or fast-twitch fibers only, but most were found in regions that contained both slow-twitch and fast-twitch extrafusal fibers. The frequency with which each fiber type occurred near tendon organs approached the frequency with which it occurred in more inclusive regions. In receptive fields with mixed fiber populations, fast-twitch fibers were the predominant type, especially in the anterior leg muscles. Distribution patterns of extrafusal fiber types adjacent to and farther removed from tendon organs suggest that afferent discharges from tendon organs are by and large unbiased measures of the contractile activity of the extrafusal fiber population of the muscle portion in which the tendon organs are located. In mixed muscle regions, slow-twitch fibers and fast-twitch fibers attach on given tendon organs, enabling them to monitor forces produced by slow motor units and by fast motor units. Most tendon organs are situated in mixed extrafusal fiber fields with high fast-twitch fiber content, indicating that in chicken leg muscles sensory feedback from tendon organs is largely one from fast motor units.

Animals↗

Type and regional diversity in the distribution of myosin heavy chains in chicken intrafusal muscle fibers.

BACKGROUND: Chicken intrafusal fibers were classified on the basis of their myosin heavy chain (MHC) composition, which was compared to that of mammalian nuclear bag and nuclear chain types. METHODS: Immunoreactivities of intrafusal fibers from leg muscles of 8-week-old chickens were evaluated in serial cross-sections after incubation with monoclonal antibodies against slow-twitch, slow-tonic, or fast-twitch MHC and fast muscle C-protein. RESULTS: Four categories of slow intrafusal fiber could be distinguished on the basis of differential expression of slow-twitch and slow-tonic MHC. Segregation into types was most evident at the motor axon supplied pole, followed by the sensory region of the equator. Fiber types were least distinct at the juxtaequator where sensory and motor axons meet. Intrafusal fibers negative for slow myosins reacted with anti-fast myosins. Fast fibers were best viewed as a single group without subdivisions. Immunostaining for fast muscle C-protein paralleled in large part reactivities for neonatal/fast MHC, indicating that proteins other than MHC are useful fiber type markers. CONCLUSIONS: Despite regional changes along the length of intrafusal fibers and some variation within fiber types, the concept of separate MHC-based fiber types was valid as long as typing of fibers was restricted to the proximal polar region. Comparisons of MHC profiles revealed similarities between chicken fast intrafusal fibers and mammalian nuclear chain fibers and between some chicken slow intrafusal fibers and mammalian nuclear bag fibers.

Animals↗

Fiber transformation and replacement in low-frequency stimulated rabbit fast-twitch muscles.

The fast-to-slow conversion of rabbit skeletal muscles by chronic low-frequency (10 Hz, 12 h daily) stimulation involves (1) sequential fast-to-slow fiber-type transitions in the order of type IID-->type IIA-->type I, and (2) the replacement of deteriorating fast-twitch glycolytic fibers by new fibers derived from satellite cells and myotubes. These two processes were analyzed in 30- and 60-day stimulated extensor digitorum longus and tibialis anterior muscles. Fast-to-slow transforming fibers were identified by myofibrillar actomyosin histochemistry as type C fibers and immunohistochemically by their reaction with monoclonal antibodies specific to slow and fast myosin heavy chain isoforms. In situ hybridization of mRNA specific to the myosin heavy chain I isoform identified all fibers expressing slow myosin, i.e., type I and C fibers. The fraction of transforming fibers ranged between 35% and 50% in 30-day stimulated muscles. The percentage of type I fibers (20%) was threefold elevated in extensor digitorum longus muscle, but unaltered (3.5%) in tibialis anterior muscle, suggesting that fast-to-slow fiber conversion was more advanced in the former than in the latter. Fiber replacement was indicated by the finding that the fiber populations of both muscles contained 15% myotubes or small fibers with central nuclei. In situ hybridization revealed that myotubes and small regenerating fibers uniformly expressed myosin heavy chain I mRNA. Similarly, high percentages of slow-myosin-expressing myotubes and small fibers were found in 60-day stimulated muscles.

Adenosine Triphosphatases↗

Endothermic force generation in fast and slow mammalian (rabbit) muscle fibers.

Isometric tension responses to rapid temperature jumps (T-jumps) of 3-7 degrees C were examined in single skinned fibers isolated from rabbit psoas (fast) and soleus (slow) muscles. T-jumps were induced by an infrared laser pulse (wavelength 1.32 microns, pulse duration 0.2 ms) obtained from a Nd-YAG laser, which heated the fiber and bathing buffer solution in a 50-microliter trough. After a T-jump, the temperature near the fiber remained constant for approximately 0.5 s, and the temperature could be clamped for longer periods by means of Peltier units assembled on the back trough wall. A T-jump produced a step decrease in tension in both fast and slow muscle fibers in rigor, indicating thermal expansion. In maximally Ca-activated (pCa approximately 4) fibers, the increase of steady tension with heating (3-35 degrees C) was approximately sigmoidal, and a T-jump at any temperature induced a more complex tension transient than in rigor fibers. An initial (small amplitude) step decrease in tension followed by a rapid recovery (tau(1); see Davis and Harrington, 1993) was seen in some records from both fiber types, which presumably was an indirect consequence of thermal expansion. The net rise in tension after a T-jump was biexponential, and its time course was characteristically different in the two fibers. At approximately 12 degrees C the reciprocal time constants for the two exponential components (tau(2) and tau(3), respectively, were approximately 70.s(-1) and approximately 15.s(-1) in fast fibers and approximately 20.s(-1) and approximately 3.s(-1) in slow fibers. In both fibers, tau(2) ("endothermic force regeneration") became faster with an increase in temperature. Furthermore, tau(3) was temperature sensitive in slow fibers but not in fast fibers. The results are compared and contrasted with previous findings from T-jump experiments on fast fibers. It is observed that the fast/slow fiber difference in the rate of endothermic force generation (three- to fourfold) is considerably smaller than the reported differences in the "phosphate release steps" (> 30-fold).

Adenosine Triphosphatases↗

Analysis of fiber type transformation and histology in chronic electrically stimulated canine rectus abdominis muscle island-flap stomal sphincters.

Dynamic skeletal muscle flaps are designed to perform a specific functional task through contraction and relaxation of their muscle fibers. The most commonly used dynamic skeletal flaps today are for cardiomyoplasty and anal or urinary myoplasty. Low-frequency chronic stimulation of these flaps enables them to use their intrinsic energy stores in a more efficient manner through aerobic metabolic pathways for increased endurance and improved work capacity. The purpose of this study was to (1) determine whether fiber type transformation from fatigue-prone (type II) muscle fibers to fatigue-resistant (type I) muscle fibers could be demonstrated in the authors' chronic canine stomal sphincter model where the rectus abdominis muscle was used to create a functional stomal sphincter, (2) assess whether there is any correlation between the degree of muscle fiber type transformation and the continence times, and (3) examine the long-term effects of the training regimens on the skeletal muscle fibers through histologic and volumetric analysis. Eight dynamic island-flap sphincters were created from a part of the rectus abdominis muscle in mongrel dogs by preserving the deep inferior epigastric vascular pedicle and the most caudal investing intercostal nerve. The muscular sphincters were wrapped around a blind loop of distal ileum and trained with pacing electrodes. Two different training protocols were used. In group A (n = 4), a preexisting anal dynamic graciloplasty training protocol was used. A revised protocol was used in group B (n = 4). Muscle biopsy specimens were obtained before and after training from the rectus abdominis muscle sphincter. Fiber type transformation was assessed using a monoclonal antibody directed against the fatigue-prone type II fibers. Pretraining and posttraining skeletal muscle specimens were examined histologically. A significant fiber type conversion was achieved in both group A and group B animals, with each group achieving greater than 50 percent conversion from fatigue-prone (type II) muscle fibers to fatigue-resistant (type I) muscle fibers. The continence time was different for both groups. Biopsy specimens 1 cm from the electrodes revealed that fiber type transformation was uniform throughout this region of the sphincters. Skeletal muscle fibers within both groups demonstrated a reduction in their fiber diameter and volume. Fiber type transformation is possible in this unique canine island-flap rectus abdominis sphincter model. The relative design of the flap with preservation of the skeletal muscle resting length and neuronal and vascular supply are important characteristics when designing a functional dynamic flap for stomal continence.

Animals↗

Denervation produces different single fiber phenotypes in fast- and slow-twitch hindlimb muscles of the rat.

Using a single, mechanically skinned fiber approach, we tested the hypothesis that denervation (0 to 50 days) of skeletal muscles that do not overlap in fiber type composition [extensor digitorum longus (EDL) and soleus (SOL) muscles of Long-Evans hooded rats] leads to development of different fiber phenotypes. Denervation (50 day) was accompanied by 1) a marked increase in the proportion of hybrid IIB/D fibers (EDL) and I/IIA fibers (SOL) from 30% to >75% in both muscles, and a corresponding decrease in the proportion of pure fibers expressing only one myosin heavy chain (MHC) isoform; 2) complex muscle- and fiber-type specific changes in sarcoplasmic reticulum Ca(2+)-loading level at physiological pCa approximately 7.1, with EDL fibers displaying more consistent changes than SOL fibers; 3) decrease by approximately 50% in specific force of all fiber types; 4) decrease in sensitivity to Ca(2+), particularly for SOL fibers (by approximately 40%); 5) decrease in the maximum steepness of the force-pCa curves, particularly for the hybrid I/IIA SOL fibers (by approximately 35%); and 6) increased occurrence of biphasic behavior with respect to Sr(2+) activation in SOL fibers, indicating the presence of both slow and fast troponin C isoforms. No fiber types common to the two muscles were detected at any time points (day 7, 21, and 50) after denervation. The results provide strong evidence that not only neural factors, but also the intrinsic properties of a muscle fiber, influence the structural and functional properties of a particular muscle cell and explain important functional changes induced by denervation at both whole muscle and single cell levels.

Animals↗

Single muscle fiber adaptations with marathon training.

The purpose of this investigation was to characterize the effects of marathon training on single muscle fiber contractile function in a group of recreational runners. Muscle biopsies were obtained from the gastrocnemius muscle of seven individuals (22 +/- 1 yr, 177 +/- 3 cm, and 68 +/- 2 kg) before, after 13 wk of run training, and after 3 wk of taper. Slow-twitch myosin heavy chain [(MHC) I] and fast-twitch (MHC IIa) muscle fibers were analyzed for size, strength (P(o)), speed (V(o)), and power. The run training program led to the successful completion of a marathon (range 3 h 56 min to 5 h 35 min). Oxygen uptake during submaximal running and citrate synthase activity were improved (P < 0.05) with the training program. Muscle fiber size declined (P < 0.05) by approximately 20% in both fiber types after training. P(o) was maintained in both fiber types with training and increased (P < 0.05) by 18% in the MHC IIa fibers after taper. This resulted in >60% increase (P < 0.05) in force per cross-sectional area in both fiber types. Fiber V(o) increased (P < 0.05) by 28% in MHC I fibers with training and was unchanged in MHC IIa fibers. Peak power increased (P < 0.05) in MHC I and IIa fibers after training with a further increase (P < 0.05) in MHC IIa fiber power after taper. These data show that marathon training decreased slow-twitch and fast-twitch muscle fiber size but that it maintained or improved the functional profile of these fibers. A taper period before the marathon further improved the functional profile of the muscle, which was targeted to the fast-twitch muscle fibers.

Adaptation, Physiological↗

Fiber type composition of abdominal muscles in Japanese macaques (Macaca fuscata).

The muscle fiber composition and cross-sectional area of muscle fiber types were investigated histochemically in the abdominal muscles (rectus abdominis muscle, obliquus externus abdominis muscle, obliquus internus abdominis muscle and transversus abdominis muscle) of three Japanese macaques (Macaca fuscata). Muscle fibers were classified into three fiber types (Type I, II A and II B) by myosin ATPase activity and succinate dehydrogenase activity. Each abdominal muscle in Japanese macaques contained high proportion of Type II B fibers and there were no large differences in the fiber type composition between the abdominal muscles. The range of mean fiber type percent was 26-32% Type I, 21-22% Type II A, and 46-52% Type II B fibers. Thus, based on the histochemical fiber type composition, the separate abdominal muscles appear to have a similar functional capacity. The cross-sectional area was larger for Type II than for Type I fibers, and the areas were similar in Type II A and Type II B fibers in each muscle. The rectus abdominis showed larger fibers of each type compared to the lateral abdominal muscles. The high proportion of Type II B fibers and large fiber size for Type II B fibers suggest that the abdominal muscles of Japanese macaques have properties similar to the propulsive and locomotory muscles in the limbs.

Abdominal Muscles↗

Histochemical evidence of altered development of cholinergic fibers in the rat dentate gyrus following lesions. II. Effects of partial entorhinal and simultaneous multiple lesions.

It has been concluded previously that the septohippocampal fibers which project to the rat dentate gyrus extend or branch in the denervated area of the molecular layer following a complete ipsilateral entorhinal lesion. The septohippocampal fibers thus appear to replace some of the perforant fibers which degenerate as a result of the lesion. The reactive fibers eventually become localized to a much smaller and more superficial area after lesions of immature rats than after lesions made in adulthood. To determine whether this difference in the response results from a selective reaction to loss of the lateral perforant path in the immature rat, various portions of the entorhinal cortex were removed at the age of 11 days, and the cholinergic septohippocampal fibers were visualized by acetylcholinesterase histochemistry. An alternative possibility, that the difference between immature and adult rats is attributable to an interaction with other reactive afferents, was tested by removing other sources of input (the contralateral entorhinal cortex, contralateral hippocampal formation or both) along with the ipsilateral entorhinal cortex at the age of 11 days and then demonstrating the septohippocampal fibers histochemically. Lesions of the lateral part of the ipsilateral entorhinal cortex (source of the lateral perforant path) at 11 days of age evoked a septohippocampal reaction along the outer edge of the molecular layer, where the lateral perforant path fibers normally terminate. This result matched that produced by a complete entorhinal lesion. Lesions of the medial entorhinal cortex evoked no obvious reaction. In contrast, the septohippocampal fibers in adult rats proliferated in the denervated area of the molecular layer after lesions of either part of the entorhinal cortex. Combining lesions of other sources of innervation to the dentate gyrus with an ipsilateral entorhinal lesion at 11 days of age did not alter the response of septohippocampal fibers, as determined histochemically. Neither did the septohippocampal fibers react to removal of commissural afferents alone. The response at any age was unaffected by prior or subsequent removal of the contralateral entorhinal cortex. These results indicate that in immature rats the septohippocampal fibers respond only to loss of the lateral perforant path, but these same fibers can later react to loss of any part of the perforant path. They are regarded as support for the hypothesis that the reactive septohippocampal fibers preferentially interact with dendritic growth cones. Our results do not support explanations based on a hypothetical attraction between septohippocampal and crossed perforant path fibers (which react in the same area) or on competition with commissural fibers (which reinnervate an adjacent area). We suggest further that proximity to the degenerating elements does not in itself determine the pattern of reinnervation after lesions of the central nervous system.

Acetylcholinesterase↗

Early climbing fiber interactions with Purkinje cells in the postnatal mouse cerebellum.

The time and place of initial contacts between afferent axons and their target cells are not known for most regions of the mammalian CNS. To address this issue, we have selectively visualized afferent climbing fiber axons together with their synaptic targets, Purkinje cells, in postnatal mouse cerebellum. Climbing fibers were orthogradely labeled by injection of rhodamine isothiocyanate into their brainstem source, the inferior olivary nucleus. Purkinje cells were localized with an antibody to a calcium-binding protein, calbindin D-28k (CaBP), in the same section or in adjacent sections. A novel view of the olivocerebellar projection and the morphology of climbing fiber arbors prior to the well-known "nest" stage has emerged from this analysis. At birth, climbing fibers project into the zone of Purkinje cells, before these cells have aligned into a monolayer. During this phase, climbing fibers have simple morphologies consisting of relatively unbranched terminal arbors and small tapered growing tips. Purkinje cells are arranged 3-6 cells deep and have tufted dendrites and relatively smooth somata. By postnatal days 3-4, climbing fibers branch over several adjacent Purkinje cell perikarya, which are still organized in a band several cells thick. From postnatal days 5-7, when climbing fibers subsequently make focused nests on individual cells, Purkinje somata are smoother and form a more distinct monolayer. Up to this time, however, climbing fibers continue to associate with Purkinje perikarya, even though Purkinje cell dendrites have emerged and branched extensively. By postnatal days 8-10, climbing fiber terminals climb onto the trunk of the relatively mature Purkinje dendritic tree. At birth, mossy fibers originating from the pontine nuclei resemble immature climbing fibers in that they also have a simple unbranched morphology and growing tips, but project only so far as the internal granule cell layer. Occasional individual fibers reach into the Purkinje zone both at postnatal day 0 and postnatal day 4, confirming that the fibers formerly described as "combination fibers" (Mason and Gregory, S4. J. Neurosci, 4:1715-1735) can be mossy in origin. These data demonstrate that climbing fibers project among Purkinje cells earlier than suspected, before these afferents begin to arborize and form pericellular nests. Our observations are not in accord with the view derived from autoradiographic tracing studies that as in other cortical areas, climbing afferents wait in the vicinity of Purkinje cells in the early neonatal period, then advance onto these cells in synchrony with Purkinje cell alignment into a monolayer and dendritic maturation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Dynamic changes in the density of radial glial fibers of the developing murine cerebral wall: a quantitative immunohistological analysis.

The density of radial glial fibers in the developing murine cerebral wall decreases dramatically during the terminal week of gestation. The present analysis characterizes these variations of fiber density quantitatively. Radial glial fibers were stained with monoclonal antibody RC2. Fibers were counted in a standard area of 2,000 microns2, passing orthogonally to the fiber long axis. At E14, fiber density is maximum and relatively uniform throughout the full width of the cerebral wall. Subsequently, the overall glial fiber density decreases and fiber density gradients emerge in the transmural span of fibers. These radial fiber density gradients are marked by sharp declines at the level of the ventricular-subventricular zone and in the zone of transition between intermediate zone (IZ) and cortical plate. In the interval E14-P0, the decrease in densities of fibers crossing the IZ is commensurate with the predicted diluting effects of tissue expansion with growth. By contrast, the decrease in fiber densities in ascent across the cortical plate beyond E14 through E17 exceeds that predicted by growth. The observations suggest that a substantial population of radial glial fibers do not span the full ventricular zone to the cerebral surface. A major contingent appears to extend only as far as the external sagittal stratum/subplate through E16. Subsequently, at a time when supragranular cortical layers are being assembled, the full set of fibers appears to extend more uniformly through the cortical strata. The late surge of fibers would be appropriate to the intercalation of groupings of neurons of the supragranular layers.

Animals↗

Dissolution of short and long rockwool and glasswool fibers by macrophages in flowthrough cell culture.

Dissolution of MMVF (man-made vitreous fibers) by macrophages has previously been studied utilizing cell cultures in wells. A new, more dynamic method has been developed to explore the effects of macrophages on MMVF dissolution. In this method, the culture medium flows through a membrane on which the macrophages and fibers are placed. The dissolution of short and long rockwool and glasswool fibers was investigated in the present study by macrophages by assessing the dissolution of Si (silicon), Fe (iron), and Al (aluminium) from the fibers. Dissolution of these elements usually increased as a function of time. Generally, the dissolution of elements from the fibers in the flowthrough culture exceeded that observed with the culture in wells system. The dissolution of glasswool fibers was greater in medium than in cell culture, whereas the opposite was true for rockwool fibers. Dissolution of Si was greater from glasswool than from rockwool fibers, while the opposite was true for Fe and Al. Macrophages that had phagocytized fibers in flowthrough culture contained Si, and there were also precipitations with Si in the samples. The fibers in the flowthrough culture also exhibited surface changes such as breakings, pittings, etching, and peeling. The short rockwool fibers tended to fracture more than short glasswool fibers, while long glasswool fibers were more extensively broken than short glasswool fibers. The results with this new, dynamic, flowthrough culture method with macrophages demonstrate that this method provides valuable information on the abilities of macrophages to dissolve MMVF leading to subsequent morphological changes of fibers.

Aluminum↗

Expression of polysialylated NCAM but not L1 or N-cadherin by regenerating adult mouse optic fibers in vitro.

This study asks if there might be irreversible maturational changes in adult neurons that limit their capacity to regenerate. Retina from adult and embryonic mouse were placed in culture on laminin substrates so that regenerating adult optic fibers could be compared to growing embryonic fibers. Several cell adhesion molecules (CAMs) known to mediate the growth of embryonic neurites on astrocytes were assayed by immunocytochemistry: L1, N-cadherin, and NCAM. Thy 1.2, a potential CAM with inhibitory activity, was also examined. As in vivo, embryonic fibers were found to express both L1 and N-cadherin. In contrast, regenerating adult fibers had no detectable amounts of either of these CAMs. N-Cadherin is normally down regulated during development so its absence in adult fibers suggests it can not be reexpressed during regeneration. L1 is normally found in the proximal regions of adult optic fibers so its absence indicates it is not expressed or transported in regenerating fibers. Adult regenerating fibers expressed high levels of Thy 1.2, which was undetectable in embryonic optic fibers. Thy 1.2 is normally found in mature fibers, indicating this phenotypic feature is preserved during regeneration. Both adult and embryonic fibers showed strong reactivity for NCAM, which in vivo is normally found in embryonic and at lower levels in adult fibers. Surprisingly, both embryonic and regenerating adult fibers expressed high levels of polysialic acid, which is normally absent in adult fibers. NCAM may be one of few CAMs available to adult optic fibers for regeneration on astrocytes.

Animals↗

Oxygen diffusion coefficient in isolated chicken red and white skeletal muscle fibers in ontogenesis.

Oxygen diffusion from medium to cultured isolated muscle fibers from red gastrocnemius muscle (deep part) (RGM) and white pectoralis muscle (WPM) of embryonic and postnatal chickens (about 6 months) was explored. The intracellular effective O(2) diffusion coefficient (D(i)) in muscle fiber was calculated from a model of a cylindrical fiber with a uniform distribution of an oxygen sink based on these experimentally measured parameters: critical tension of O(2) (PO(2)) on the surface of a fiber, specific rate of O(2) consumption by a weight unit of muscle fibers (;VO(2)), and average diameter of muscle fibers. The results document the rapid hypertrophic growth of RGM fibers when compared to WPM fibers in the second half of the embryonic period and the higher values of;VO(2) and critical PO(2) during the ontogenetic period under study. The oxygen D(i) in RGM fibers of embryos and 1-day chickens was two to three times higher than observed for WPM fibers. For senior chickens, the oxygen D(i) value in RGM and WPM fibers does not differ. The D(i) of O(2) in both RGM and WPM fibers increased from 1.4-2.7 x 10(-8) to 90-95 x 10(-8) cm(2)/s with an ontogenetic increase in fiber diameter from 7. 5 to 67.0 microm. At all stages the oxygen D(i) values in RGM and WPM fibers are significantly lower than the O(2) diffusion coefficient in water: for 11-day embryos they are 889 and 1714 times lower and for adult individuals 25 and 27 times lower, respectively. Why oxygen D(i) values in RGM and WPM fibers are so low and why they are gradually increasing during the course of hypertrophic ontogenetic growth are still unclear.

Animals↗

Biopersistence of synthetic vitreous fibers and amosite asbestos in the rat lung following inhalation.

Fiber biopersistence as a major mechanism of fiber-induced pathogenicity was investigated. The lung biopersistence of 5 synthetic vitreous fibers (SVFs) and amosite asbestos was evaluated using the rat inhalation model. In contrast to several previous studies, this study examined fibers that dissolve relatively slowly in vitro at pH 7.4. Fisher rats were exposed for 5 days by nose-only inhalation to refractory ceramic fiber (RCF1a), rock (stone) wool (MMVF21), 2 relatively durable special application fiber glasses (MMVF32 or MMVF33), HT stonewool (MMVF34), amosite asbestos, or filtered air. Lung burdens were analyzed during 1 year post-exposure. Fiber aerosols contained 150-230 fibers/cc longer than 20 micrometer (>20 micrometer). On post-exposure Day 1, long-fiber lung burdens for the 6 test fibers were similar (12-16 x 10(5) fibers/lung >20 micrometer). After 1 year, the percentage of fibers >20 micrometer remaining in the lung was 0.04-10% for SVFs but 27% for amosite. Lung clearance weighted half-times (WT1/2) for fibers >20 micrometer were 6 days for MMVF34, 50-80 days for the other 4 SVFs, and >400 days for amosite. This study and 3 previous studies demonstrate a broad range of biopersistences for 19 different SVFs and 2 asbestos types. Ten of these fibers also have been (or are being) tested in chronic inhalation studies; in these studies, the very biopersistent fibers were carcinogenic (amosite, crocidolite, RCF1, MMVF32, and MMVF33), while the more rapidly clearing fibers were not (MMVF10, 11, 21, 22, and 34). These studies demonstrate the importance of biopersistence as an indicator of the potential pathogenicity of a wide range of fiber types.

Aerosols↗

Contrasting effects of water-soluble and water-insoluble dietary fibers on bile acid conjugation and taurine metabolism in the rat.

The effect of the type of dietary fiber on the bile acid and taurine metabolism was examined in rats. Diets containing 10% of various water-soluble fibers (citrus pectin, konjak mannan, guar gum) as compared to a fiber-free diet increased biliary excretion of total bile acids. In contrast, water-insoluble dietary fibers (cellulose, corn bran, chitin; 10% in the diets) as well as cholestyramine (5% in the diet) considerably decreased bile acid excretion. Water-soluble dietary fiber-mediated increases in bile acid excretion were totally attributable to increases in glycine-conjugates. Thus, these fibers greatly increased the bile acid glycine-to-taurine ratio (G/T). Excretion of glycine conjugates decreased more than that of taurine conjugates in rats fed various water-insoluble dietary fibers. As a result, G/T in rats fed water-insoluble fibers was significantly lowered as compared to G/T in animals fed a fiber-free diet. Cholestyramine did not affect the G/T ratio of bile acids. Fecal bile acid excretion and the activities of hepatic cholesterol 7 alpha-hydroxylase (EC 1.14.13.17) in rats fed various water-soluble dietary fibers approximately doubled as compared to the respective values for rats fed a fiber-free diet. Whereas cholestyramine greatly increased these parameters, water-insoluble fibers did not significantly affect them. Various water-soluble fibers decreased hepatic concentration and urinary excretion of taurine as well as the activity of hepatic cysteine dioxygenase (EC 1.13.11.20). In contrast, water-insoluble fibers considerably increased hepatic taurine concentrations and enzyme activities. The parameters for taurine metabolism were unaffected by cholestyramine. It was suggested that the types of dietary fiber affected hepatic taurine synthesis and thus modified bile acid glycine/taurine ratios.

Animals↗

Anodally focused polarization of peripheral nerve allows discrimination of myelinated and unmyelinated fiber input to brainstem nuclei.

We investigated the ability of a novel direct current (DC) polarization technique to block selectively the conduction in peripheral myelinated nerve fibers and allowing propagation in only unmyelinated fibers. In anesthetized adult rats, distal branches of the sciatic nerve (caudal cutaneous sural and tibial nerves) were exposed for electrical stimulation of A- and C-fibers. Two specially fabricated trough electrodes of different size and surface area were placed onto the sciatic nerve. Through these proximal electrodes a controlled ramped DC was timed to coincide with the arrival of A- and C-fiber action potentials, evoked electrically at the distal nerves or naturally from the foot or ankle, with the intent of blocking propagation in A-fibers while allowing C-fiber throughput. Neuronal recordings were made both peripherally (proximal sciatic nerve fascicles or L5 dorsal roots) and centrally (single cells in the nucleus gracilis or nucleus reticularis gigantocellularis). The DC polarization was shown to block conduction in myelinated A-fibers effectively, while allowing conduction in the unmyelinated C-fibers, without activation of fibers via the DC polarization itself. This was dependent upon the following factors: electrode polarity, onset rate of polarization, peak amplitude of polarization, distance between polarizing electrodes, size difference between polarizing electrodes, and gross nerve size. These experiments demonstrate that anodally focused DC polarization, applied utilizing two trough electrodes of different sizes, is capable of effectively, reversibly, and reproducibly blocking conduction in myelinated A-fibers evoked either electrically or naturally, while still allowing conduction to occur in the unmyelinated C-fiber population. In the context of experimental usage, we have demonstrated blocking of low-threshold A-fiber, but not C-fiber, mediated inputs to the caudal brainstem. This technique should find wide application in studies involving the processing of information conveyed centrally by the unmyelinated C-fiber afferent population, including discriminating afferent responses to peripheral stimuli, the role of C-fiber input in reflex activity, and the plasticity following injury or other manipulations.

Action Potentials↗

Distribution and coexistence of peptides in nerve fibers of the external muscle of the human gastrointestinal tract.

The nerve fibers that supply the external muscle of the human gastrointestinal tract were examined for their immunoreactivity to the neuropeptides enkephalin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide, for tyrosine hydroxylase (a catecholamine-synthesizing enzyme), and for coexistence between immunoreactivities in nerve fibers. Studies on coexistence revealed that the majority of reactive nerve fibers could be placed in one of two classes: (a) those fibers with reactivity to enkephalin or substance P, or both, and (b) fibers containing one or both of the peptides neuropeptide Y and vasoactive intestinal peptide. Many fibers immunoreactive for vasoactive intestinal peptide or neuropeptide Y, or both, were found throughout the external smooth muscle of the gastrointestinal tract, but neuropeptide Y-reactive fibers were less common in the small and large intestines than in the stomach and esophagus. Fibers immunoreactive for enkephalin or substance P, or both, were sparse in the esophagus, increased in numbers to reach maximal frequency in the pylorus, and maintained a similar frequency in the small and large intestines. Fibers with somatostatin or tyrosine hydroxylase immunoreactivity were rare. In general, sphincter regions were similar to nonsphincter regions in peptide-immunoreactive fiber numbers and types, except that the internal anal sphincter had no enkephalin-immunoreactive fibers and very few substance P-reactive fibers. Moderate numbers of fibers reactive for neuropeptide Y and vasoactive intestinal peptide were found in the internal anal sphincter. It is suggested that enkephalin and substance P are in excitatory fibers and that vasoactive intestinal peptide and neuropeptide Y are in fibers inhibitory to the external muscle.

Adult↗