Malignant astrocytoma with binucleated granular cells in a Sprague-Dawley rat.

A 2-year-old Sprague-Dawley rat with hindlimb paralysis was diagnosed with a cerebral malignant astrocytoma. The distinctive feature of this astrocytoma was the presence of scattered binucleated cells that contained hypereosinophilic, 1-2 micro m in diameter, cytoplasmic granules. The neoplastic astrocytes stained positively for vimentin (VIM), lysozyme, and phosphotungstic acid hematoxylin (PTAH). Within the binucleated cells, granules stained with PTAH and periodic acid-Schiff (PAS) before and after diastase digestion. Ultrastructurally, neoplastic astrocytes were characterized by cytoplasmic aggregates of electron-dense intermediate filaments consistent with VIM and desmin. The cytoplasm of binucleated cells contained numerous phagolysosomes enlarged by myelin figures and glycoprotein or glycolipid. Intermediate filaments were not present. This is the first description, in the rat, of a neoplasm with features resembling the human granular cell astrocytoma. Our findings suggest that an astrocytic origin should be considered for the binucleated cells in this neoplasm.

Myostatin expression in age and denervation-induced skeletal muscle atrophy.

Myostatin is hypothesized to regulate skeletal muscle mass and to be a potential target for therapeutic intervention in sarcopenia. To clarify whether myostatin is invariably associated with sarcopenia, this study examined the levels of expression of myostatin mRNA and protein in Sprague Dawley rats during aging- and denervation-induced sarcopenia. The level of myostatin mRNA in the gastrocnemius decreased progressively with age being 9, 34 and 56% lower at 6, 12 and 27 months, respectively, compared with mRNA levels at 1.5 months. In contrast, two low molecular mass isoforms of myostatin protein identified by Western blotting increased progressively with age. With denervation, myostatin mRNA was 31% higher on day 1 but by 14 days after sciatic neurectomy when the muscle had atrophied 50%, myostatin expression decreased 34% relative to the sham operated limb. Western analysis of the denervated gastrocnemius showed that myostatin protein levels varied in parallel with mRNA. These disparate patterns of expression of myostatin during age- and denervation-induced atrophy suggest that the regulation of myostatin is complex and variable depending on whether the atrophy is slowly or rapidly progressive.

Disparate dysfunction of skeletal muscles located near and distant from burn site in the rat.

This study tested the hypotheses that burn-induced change in muscle function varies at sites local and distant from burn and is related to changes in expression of acetylcholine receptors (AChRs) and muscle mass. In anesthetized rats, approximately 4% burn was inflicted over the tibialis anterior muscle of one limb. The contralateral leg served as control. In another study, a approximately 45% body surface area burn was produced on the trunk; controls were body sham-burned rats. The evoked twitch tensions of tibialis anterior muscles in both legs were measured together with AChR proteins and their transcripts. Compared with the contralateral leg, absolute tensions in the burned leg declined at days 1, 4, and 7 without loss of muscle mass so that tension per unit wet muscle mass (specific tension) decreased; at day 14, the tension decreased with muscle atrophy so that specific tension was unchanged. Membrane AChRs and/or the immature subunit transcript, AChRgamma messenger ribonucleic acid (mRNA) increased at days 4, 7, and 14, and both were inversely related to evoked tension (r =.43, P <.01 and r =.61, P <.0001, respectively). There was a direct correlation between AChR and AChRgamma mRNA (r =.82, P <.001), suggesting that the upregulated AChRs may contain the immature gamma-subunit isoform. After approximately 45% body burn, AChRs and mRNA did not change and the evoked tensions did not decline, but there was relative loss of muscle mass at days 7 and 14 so that specific tension increased. Burn trauma initially causes weakness of muscles directly under the burn, and this weakness may be partially related to increased expression of immature AChRs and later to muscle atrophy.

Long-term denervation impairs insulin receptor substrate-1-mediated insulin signaling in skeletal muscle.

Long-term denervation is associated with insulin resistance. To investigate the molecular bases of insulin resistance, the downstream signaling molecules of insulin receptor including insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI 3-K) were examined in skeletal muscle of rats after 7 days of denervation. Long-term denervation attenuated insulin-stimulated activation of the initial steps of the intracellular signaling pathway. Insulin-stimulated tyrosine phosphorylation of insulin receptor was reduced to 36% (P < .005), as was the phosphorylation of IRS-1 to 34% (P < .0001) of control. While insulin receptor protein level was unchanged, the protein expression of IRS-1 was significantly decreased in denervated muscles. Insulin-stimulated percent tyrosine phosphorylation of IRS-1, normalized to the IRS-1 protein expression, was also reduced to 55% (P < .01) of control in denervated muscle. Denervation caused a decline in the insulin-induced binding of p85 regulatory subunit of PI 3-K to IRS-1 to 61% (P < .001) and IRS-1-associated PI 3-K activity to 57% (P < .01). These results provide evidence that long-term denervation results in insulin resistance because of derangements at multiple points, including tyrosine phosphorylation of insulin receptor and its downstream signaling molecule, IRS-1, protein expression of IRS-1, and activation of PI 3-K.

Thermal injury induces greater resistance to d-tubocurarine in local rather than in distant muscles in the rat.

UNLABELLED: We tested the hypothesis that resistance to d-tubocurarine (dTC) is more intense in muscles closer to, than distant from, burn, and is related to the expression of immature and total acetylcholine receptors (AChRs). Anesthetized rats received approximately 4% surface area burn over the tibialis muscle of one leg with the contralateral leg serving as control, or approximately 45% of the flank burn, with sham-burned pair fed controls. At 1, 4, 7, or 14 days later, the 50% effective dose of dTC, membrane AChRs, and messenger ribonucleic acid (mRNA) that encode the AChR gamma-subunit (AChRgamma-mRNA) were quantified in the tibialis. After the local leg burn, AChRs increased at Days 4, 7, and 14, and AChRgamma-mRNA at Days 4 and 7 after burn. The increased AChRgamma-mRNA correlated with total AChRs (r = 0.82), suggesting that the up-regulated AChRs may contain the immature isoform. The 50% effective dose of dTC after the local leg burn increased 1.2- to 1.5-fold at all periods and correlated significantly with AChRs (r = 0.54) and AChRgamma-mRNA (r = 0.57). After the flank burn, resistance was seen at Day 14 in association with muscle atrophy; AChRs and AChRgamma-mRNA were unaltered. The resistance to dTC after a local burn occurs sooner, is more marked, and is probably related to both increases and isoform changes in AChRs. The resistance at distant muscles appears unrelated to AChR changes. IMPLICATIONS: The resistance to d-tubocurarine after a burn differs between muscles near and distant from the burn and seems to depend on quantitative and qualitative changes in acetylcholine receptors and muscle atrophy associated with the insult.

Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression.

UNLABELLED: Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg/kg prednisolone (P10 group), 100 mg/kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose-response curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d-tubocurarine (microg/kg) in the tibialis muscle was smaller in the P10 (33.6 +/- 5.4) than in the S (61.9 +/- 5.0) or the P100 (71.3 +/- 9.6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r(2) = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose of d-tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose-dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression. IMPLICATIONS: The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose-dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression.

Fiber atrophy, but not changes in acetylcholine receptor expression, contributes to the muscle dysfunction after immobilization.

OBJECTIVES: Muscle weakness associated with critical illness can be due to the illness itself, immobilization associated with it, and/or to concomitant use of drugs that affect neuromuscular transmission. This study investigated the contribution of immobilization per se to the muscle dysfunction, as well as the associated morphologic and biochemical changes. DESIGN: Prospective, laboratory study. SETTING: Hospital research laboratory. SUBJECTS: Adult, male, Sprague-Dawley rats, weighing 200 to 250 g, were randomly allocated to three experimental groups, depending on the duration (7, 14, or 28 days) of limb immobilization (n = 9 to 11 per group) or sham immobilization (n = 5 to 6 per group). INTERVENTIONS: Chronic, unilateral immobilization (disuse) of the tibialis cranialis muscle was produced by fixing the knee and ankle joints at 90 degrees flexion. The contralateral unimmobilized leg and a separate group of sham-immobilized legs served as controls. MEASUREMENTS AND MAIN RESULTS: After 7, 14, or 28 days of disuse of the tibialis muscles, the peak isometric twitch (Pt) and tetanic (Po) tensions, as well as fatigability during 5 secs of nerve stimulation at 50, 100, and 150 Hz, were measured simultaneously in situ in the immobilized group and in its contralateral control, and in the sham-immobilized group and in its contralateral control. Muscle fiber and endplate morphologies were determined by histochemical methods; membrane acetylcholine receptors (AChRs) were determined by 125I alpha-bungarotoxin assay; and the level of expression of AChR subunit transcripts was determined by reverse transcriptase-polymerase chain reaction. Immobilization reduced Pt, Po, fatigability, muscle mass, and fiber cross-sectional area (p<.001 vs. controls), but did not decrease tension per unit muscle mass, fiber oxidative capacity, or motor endplate size. Muscle mass correlated with fiber cross-sectional area. Changes in fiber cross-sectional area accounted for 23% and 46% (p< or =.043) of the variability in Pt and Po, respectively. Pt and Po correlated poorly with total AChR protein and expression of epsilon- and gamma-subunit messenger RNA. CONCLUSION: To the extent that the immobilization model simulates the disuse-induced muscle dysfunction of critical illness, the results suggest that disuse per se may contribute to the muscle weakness, and that the muscle weakness is explained, almost exclusively, by the fiber atrophy and not by the qualitative or quantitative changes in AChR expression.

Morphological correlates of the differential responses of muscles to vecuronium.

We have noted previously that duration of vecuronium block correlated with fibre size in six muscle groups in the goat. Electrophysiological considerations suggest that the important factor should be the number of acetylcholine receptors (AChR) relative to fibre size. However, this hypothesis could not be verified in the goat because the number of AChR was relatively constant in the different muscles despite differences in fibre size. Therefore, in this study, we have investigated the relationship between sensitivity to vecuronium, as reflected by the ED50 and duration of block, of six muscles in the cat and the number of AChR per unit fibre cross-sectional area (CSA). The ED50 and duration of action (time to 50% recovery of the first twitch after a dose of 15 micrograms kg-1) of vecuronium in the tibialis cranialis, soleus, rectus abdominis, masseter, diaphragm and thyroarytenoideus muscles were determined during train-of-four stimulation and EMG recording in seven cats anaesthetized with pentobarbital. CSA of the muscle fibres and number of junctional AChR in these muscles were measured by histological methods and 125I-alpha-bungarotoxin binding assay, respectively, and the number of AChR per unit fibre CSA calculated. The association between muscle response (ED50 and duration of block) and fibre CSA or number of AChR per unit fibre CSA was then tested by regression analyses. Duration of block varied between the six muscles (mean 8.9 (SEM 2.6) to 20.3 (3.1) min; P = 0.0001) but ED50 did not (7.5 (1.5) to 15.6 (2.5) micrograms kg-1; P = 0.185). Fibre CSA and number of AChR per unit fibre CSA also varied between these muscles (P = 0.0001). Duration to 50% TI recovery was prolonged in muscles with a low number of AChR relative to fibre CSA (r2 = 0.30; P = 0.0002) and the ED50 increased as the number of AChR per fibre CSA increased (r2 = 0.240; P = 0.0016). These results in the cat suggest that the number of junctional AChR relative to fibre CSA is a morphological predictor of the differential sensitivities of muscles to neuromuscular blocking agents.

Mechanisms for the paradoxical resistance to d-tubocurarine during immobilization-induced muscle atrophy.

This study investigated whether immobilization-induced hyposensitivity to d-tubocurarine (dTC), up-regulation of acetylcholine receptors (AChRs) and changes in fiber size and motor endplate size persist indefinitely and whether they are causally related. Unilateral disuse of the tibialis muscle was produced in adult rats by pinning the knee and ankle joints at 90 degrees flexion. The contralateral unpinned and a separate group of sham-pinned legs served as controls. After 7, 14 or 28 days of disuse, the in vivo dose of dTC that produced 50% depression of nerve-evoked twitch (ED50) in the tibialis muscle increased 3.0-, 3. 2- and 2.1-fold (P < .05), and membrane AChRs increased 6.0- (P < . 05), 6.3- (P > .05) and 1.2-fold (P > .395) relative to control, respectively. Disuse caused muscle fiber atrophy (P < .01) but did not affect endplate size. Hence, the ratio of endplate size to fiber size increased. There was a transient increase in gene expression of all (including de novo expression of the gamma) subunits of the AChR, peaking at day 7 and returning to normal by day 28 of immobilization. The ED50 of dTC correlated directly with AChRs (R2 = 0.51; P < .0001) or the ratio of endplate size to fiber size (R2 = 0. 30; P < .001), and inversely with fiber size (R2 = 0.43, P < .0001). It is proposed that acting together, but not singly, the changes in AChRs, fiber size and relative endplate size contribute to the magnitude and time course of the resistance to dTC produced by chronic disuse.

Tacrine does not alter the potency of succinylcholine in the rat.

PURPOSE: Tacrine is a cholinesterase inhibitor used to manage Alzheimer's dementia. Given iv, it prolongs succinylcholine blockade in humans but the effects of chronic oral tacrine are not known. METHODS: Groups of adult rats were given 2.5 mg.kg-1 tacrine (chronic groups) or l ml saline (control) twice daily by gavage for one, two, four or eight weeks. An additional (acute) group received 2.5 mg.kg-1 tacrine iv. Twelve to 18 hr after the last gavage of tacrine or saline, and -20 min after iv tacrine, cumulative dose-response curves of succinylcholine were determined in the tibialis and soleus muscles in anaesthetized, ventilated rats during monitoring of evoked twitch response to indirect (nerve) train-of-four stimulation. RESULTS: The ED50 and ED95 of succinylcholine in control rats were (mean +/- SD) 204 +/- 41 and 382 +/- 96 micrograms.kg-1, respectively in the tibialis muscle, and 280 +/- 52 and 629 +/- 168 micrograms.kg-1 in the soleus muscle (P < 0.05 between muscles). In the acute and chronic tacrine groups, the mean ED50 and ED95 ranged from 166-197 and 277-396 micrograms.kg-1., respectively, in the tibialis muscle, and 248-333 and 546-667 micrograms.kg-1, in the soleus muscle. Dose responses did not differ among acute and chronic tacrine groups and the control group. CONCLUSION: Chronic oral tacrine does not alter muscle response to succinylcholine in the rat. This may not apply to Alzheimer patients receiving chronic tacrine since the interaction between acute tacrine and succinylcholine in the rat differs from that in humans.

The effects of chronic tacrine therapy on d-tubocurarine blockade in the soleus and tibialis muscles of the rat.

Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia, but it is not clear how its chronic use might affect response to nondepolarizing muscle relaxants. We determined the magnitude and time course of the effects of chronic oral THA and of intravenous (IV) THA on d-tubocurarine (dTC) blockade at the soleus and tibialis muscles. Six groups of adult rats were given 10 mg/kg THA twice daily by gavage for 1, 2, 4, or 8 wk (chronic THA groups), or 1 mL of saline twice daily by gavage for 1-8 wk (control), or IV THA approximately 20 min before (acute), and the cumulative dose-response curves of dTC at the tibialis and soleus muscles were determined during indirect train-of-four stimulation in the anesthetized, mechanically ventilated rat. The 50% effective dose (ED50) and 95% effective dose (ED95) of dTC in control rats were (mean +/- SD) 30 +/- 10 and 61 +/- 18 microg/kg in the tibialis and 32 +/- 8 and 75 +/- 19 microg/kg in the soleus; respectively. IV THA increased the ED95 of dTC 2.5- to 3-fold (P < 0.05) but did not alter the ED50. Chronic THA increased both the ED50 and ED95 of dTC 1.5- to 2-fold (P > or = 0.05), and this effect tended to decrease with duration of THA therapy. We conclude that chronic THA therapy in rats causes resistance to dTC, with a tendency for the resistance to decrease with time, probably because of down-regulation of postsynaptic acetylcholine receptors. The same may apply to Alzheimer's patients taking THA chronically.

Properties of fibres, endplates and acetylcholine receptors in the diaphragm, masseter, laryngeal, abdominal and limb muscles in the goat.

PURPOSE: Although differences in fibre composition, fibre size or acetylcholine receptor (AChR) density between muscles have often been proposed to explain the unequal sensitivities of muscles to muscle relaxant drugs, it is not clear whether or how these parameters differ among muscles or are related to one another, In this study, several muscles were examined to determine the composition and cross-sectional area (CSA) of types I and II fibres, the surface area of their motor endplates (ESA), and their AChR density. METHODS: Biopsies from the thyroarytenoideus, cricoarytenoideus dorsalis, masseter, diaphragm, transversus abdominis, rectus abdominis, gastrocnemius and soleus muscles of goats were processed by muscle histochemistry and morphometry and the ESA:CSA ratio was computed. The number and density of AChRs per endplate were estimated by 125I-alpha-bungarotoxin binding studies. RESULTS: The mean type I fibre composition (range: 0-100%), fibre diameter (28-50 microns) and the ESA:CSA ratio (0.27-1.01) differed among muscles (P = 0.0001), but there were no significant differences (P > 0.05) in the mean endplate size (577-725 microns 2) AChR number (6.6-14.5 x 10(6)) or AChR density (8,900-22,300 microns-2) probably because of marked individual variations. Fibre size increased and the ESA:CSA ratio decreased in the order laryngeal, diaphragm, jaw, limb and abdominal muscles. CONCLUSION: It is concluded that between muscles fibre size varies more than endplate size or AChR number.

Duration of succinylcholine and vecuronium blockade but not potency correlates with the ratio of endplate size to fibre size in seven muscles in the goat.

PURPOSE: Muscles differ in their response to neuromuscular relaxants. This study investigated whether (1) the relative responses of muscles is inverted between succinylcholine (SUX) and vecuronium (VEC), and (2) differences in dose-response or duration of action are related to the morphology of fibres, endplates and acetylcholine receptors (AChR) in muscles. METHODS: In goats during thiopentone anaesthesia, the evoked EMG response to indirect train-of-four stimulation was monitored and the cumulative dose-response curves and duration of action of SUX and VEC in the diaphragm, cricoary-tenoideus dorsalis, thyroarytenoideus, transversus abdominis, rectus abdominis, soleus and gastrocnemius muscles were determined and related to their fibre composition, fibre size, endplate size, endplate to fibre size ratio, AChR number or AChR density by regression analysis. RESULTS: There were no differences in the ED50S of SUX [range, 119 +/- 11 (SE) to 159 +/- 20 micrograms.kg-1] or VEC [range, 2.8 +/- 0.2 to 3.7 +/- 0.8 microgram.kg-1] among muscles. With either drug, duration to 25% or 50% T1 recovery was shortest at the laryngedl muscles and longest at abdominal muscles (P = 0.0001), and correlated directly with fibre size (r > or = 0.40; P < 0.004) and inversely with the endplate to fibre size ratio (r > or = 0.40; P < 0.008). CONCLUSION: The results show that (1) the relative responses of muscles do not differ between depolarizing and non-depolarizing relaxants; (2) the duration of blockade is shorter in muscles composed of small fibres with large endplates relative to fibre size; and (3) there is no relation between fibre type composition and sensitivity to muscle relaxants.

Succinylcholine and vecuronium blockade of the diaphragm, laryngeal and limb muscles in the anaesthetized goat.

The purpose of the study was to compare the response of the cricoarytenoideus dorsalis muscle (CD) to neuromuscular blocking drugs with those of the thyroarytenoideus (TA), diaphragm (DI) and ulnaris lateralis (UL) muscles. Evoked electromyographic response to indirect supramaximal stimulation at 1 Hz was monitored in ten adult goats under thiopentone-halothane anaesthesia. The onset time and duration of neuromuscular blockade after intravenous administration of 500 micrograms.kg-1 of succinylcholine or 4 micrograms.kg-1 of vecuronium were determined. Times to 100% paralysis in CD, TA, DI and UL after succinylcholine were (mean +/- SD) 39 +/- 11, 39 +/- 11, 42 +/- 8 and 57 +/- 8 seconds, respectively; the corresponding times for vecuronium were 5.6 +/- 2.3, 4.6 +/- 1.7, 6.0 +/- 1.9 and 9.6 +/- 1.7 min. The order of recovery to 25% spontaneous EMG activity was TA, CD, DI and UL after succinylcholine (durations: 9.7 +/- 3.6, 11.0 +/- 3.0, 15.3 +/- 1.3 and 22.0 +/- 1.2 min, respectively) but DI, CD, TA and UL after vecuronium (durations: 31.9 +/- 18.6, 35.2 +/- 19.5, 47.1 +/- 19.9 and 71.7 +/- 16.1 minutes, respectively). Thus, as in the diaphragm and thyroarytenoideus muscles, onset time and duration of succinylcholine or vecuronium blockade were shorter in the abductor muscle of the glottis, cricoarytenoideus dorsalis, than in the limb muscle.

Muscle fibre diameter and sensitivity to neuromuscular blocking drugs.

In order to investigate the relationship between muscle fibre composition or size and muscle sensitivity to neuromuscular blocking drugs, data on the fibre composition and size of the ulnaris lateralis, thyroarytenoideus, cricoarytenoideus dorsalis and diaphragm muscles of the goat were related to the rate of recovery of these muscles from suxamethonium or vecuronium block. Muscle sensitivity (time to spontaneous 25% recovery of evoked EMG response after 100% block) correlated well with fibre size, the association being significant for the diameter of type I (r > or = 0.94; P < or = 0.016) and types I and II fibres taken together (r > or = 0.95; P < or = 0.013), but not for type II fibre diameter (r < or = 0.83; P > or = 0.084), for both suxamethonium and vecuronium. There was no association between the composition of types I or II fibres in these muscles and sensitivity (r < or = 0.37; P > or = 0.546). This suggests that muscle sensitivity to both depolarizing and non-depolarizing drugs increases with fibre size, and may account partly for the unequal sensitivities of different muscles.

Histochemical and morphometric properties of muscles of the upper airway of goats.

This study investigated the histochemical and morphometric properties of fibres in laryngeal, hyoid, tongue and pharyngeal muscles which contribute in maintaining patency of the upper airway. Muscle specimens from adult female goats were stained for nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase and myosin adenosine triphosphatase activities, and the composition and size of the fibre types determined. These muscles contained types 1, 2A, 2B and 2C fibres with type 2 fibres predominating and the fibres possessed oxidative enzyme activity suggesting fast contraction speed and yet moderate resistance to fatigue. Abductor laryngeal muscles contained more type 1 fibres than the adductors. Among pharyngeal muscles fibre size and type 1 fibre composition increased progressively from the hyopharyngeus caudally. Upper airway muscles contained relatively small fibres (range of mean diameter: 25.7 to 46.1 microns) with the pharyngeal and lingualis proprius muscles containing the smallest fibres. These properties might influence the response of upper airway muscles to neuromuscular blocking drugs.

Type, diameter and distribution of fibres in some respiratory and abdominal muscles of the goat.

This study was designed to determine the histochemical properties, size and composition of fibres in the diaphragm, intercostal and abdominal muscles of goats to clarify whether reported similarities in respiratory muscle physiology between goats and humans have a structural basis. Serial sections (10 microns) of muscular tissue from adult female goats were stained for myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase activities; the fibres were classified into type I, IIA and IIB; and their mean diameter and composition were determined. Abdominal and intercostal muscles contained types I, IIA and IIB fibres in the ratio 1:1:1, and the mean diameter of the fibres ranged from 49.2 to 62.2 microns. In contrast, the diaphragm contained 58.9% type I and 41.1% type II fibres, and the latter could not be differentiated into types IIA and IIB. Diaphragmatic fibres were also smaller (36.9-40.9 microns). These findings contrast with those in humans, where the diaphragm, intercostal and abdominal muscles contain > 50% type I fibres and have fibres of identical diameter. The differences in fibre characteristics between the diaphragm, intercostal and abdominal muscles of goats and the differences between goats and humans need to be taken into consideration in interpreting the results from studies in respiratory muscle physiology.

Comparison of the effects of cassava (Manihot esculenta Crantz) organic cyanide and inorganic cyanide on muscle and bone development in a Nigerian breed of dog.

Effects of cassava (Manihot esculenta Crantz)-borne organic cyanide and inorganic cyanide in the form of sodium cyanide on bone and muscle development were investigated in eighteen dogs of Nigerian breed. After 16 weeks of stabilization in the laboratory from the time of purchase when the dogs were fed on the same diet, they were randomly assigned to three experimental groups of six dogs each. The control group was fed on rice while the other two groups were fed on either cassava (gari) or rice plus cyanide. The three diets were made isoenergetic and isonitrogenous by varying the quantity of meat incorporated into them. The results obtained after 14 weeks of feeding the respective diets indicated that there was retardation of muscle development in the gari-fed dogs. This may have resulted from gluconeogenesis from muscle protein associated with suppression of production of insulin by the pancreas in this group. The results indicated also that the effects of inorganic dietary cyanides on muscle development were different. Both forms of dietary cyanides, however, had no adverse effect on bone development.

Comparison of the effect of castration on the development of postural and non-postural muscles of mice.

The effect of castration on the development of muscle mass of postural and non-postural muscles was studied in 18 male mice (9 castrated, 9 uncastrated). Results obtained indicated that the castrated males grew faster and were bigger in body size and weight at maturity than the intact males. The bigger body size of castrated males was not due to larger muscle mass but was probably due to increased subcutaneous fat deposition. Atrophy of muscles usually observed following castration was significantly greater in the non-postural (biceps brachii) muscle of the forelimb as compared to the postural (triceps brachii) muscle of the forelimb. Conversely, the amount of reduction in muscle mass was similar in both postural (soleus) and non-postural (tibialis cranialis) muscles of the hindlimb.