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Deoxycholate amphotericin B and amphotericin B lipid complex exert additive antifungal activity in combination with pulmonary alveolar macrophages against Fusarium solani.

Fusarium spp. have emerged as important causes of invasive fungal infections in immunocompromised patients. Rabbit pulmonary alveolar macrophages (PAMs) exhibited fungicidal activity against conidia of Fusarium solani and achieved a time-dependent increase in killing. Neither deoxycholate amphotericin B (DAMB) nor amphotericin B lipid complex (ABLC) exerted a suppressive effect on PAMs by decreasing their conidiocidal activity against F. solani. On the contrary, at a concentration of 0.125 microg ml(-1), ABLC and, to a lesser degree, DAMB additively augmented the fungicidal activity of pulmonary alveolar macrophages against conidia of Fusarium solani.

Amphotericin B↗

External cephalic version induced fetal cerebral and umbilical blood flow changes are related to the amount of pressure exerted.

OBJECTIVE: To correlate the applied pressure during external cephalic version with the changes in fetal middle cerebral arterial and umbilical arterial flow before and after the procedure. DESIGN: A prospective observational study over a two-year period. SETTING: External cephalic version was performed in a university hospital. POPULATION: Sixty-nine women with singleton breech-presenting pregnancy at or above 36 weeks of gestation undergoing external cephalic version. METHODS: During external cephalic version, the operator wore a pair of pressure-sensing gloves which had thin piezo-resistive sensors positioned on the palmar surface. During each version procedure, real-time pressure readings were recorded from all sensors, and then analysed with a computer program. The amount of pressure applied over time was presented by pressure-time integral. The pulsatility indices of both fetal middle cerebral artery and umbilical artery before and after external cephalic version were measured. The changes of pulsatility indices of both middle cerebral artery and umbilical artery were presented as a ratio of the post-external cephalic version pulsatility indices to pre-external cephalic version pulsatility indices, denoted by middle cerebral artery pulsatility index ratio and umbilical artery pulsatility index ratio, respectively. The statistical correlation between pressure-time integral and middle cerebral artery pulsatility index ratio and umbilical artery pulsatility index ratio are analysed using Pearson's correlation test. MAIN OUTCOME MEASURES: Changes in pulsatility indices of fetal middle cerebral and umbilical arteries and fetal heart rate after external cephalic version. RESULTS: The overall success rate of external cephalic version was 77%. There was a significant negative correlation between pressure-time integral and both middle cerebral artery pulsatility index ratio (P= 0.001) and umbilical artery pulsatility index ratio (P= 0.012). When women were categorised according to placental site, pressure-time integral was negatively correlated with middle cerebral artery pulsatility index ratio only when the placenta was posteriorly located (P= 0.003), and with umbilical artery pulsatility index ratio only when the placenta was laterally located (P= 0.03). CONCLUSIONS: The greater the force applied during external cephalic version, the greater the reduction in pulsatility indices of middle cerebral artery and umbilical artery, indicating an increase in blood flow through these arteries. The increase in cerebral blood flow after external cephalic version is more prominent when the placenta is lying posteriorly, while the increase in umbilical flow is more prominent when the placenta is lying laterally. These findings suggest that the vascular changes probably represent a direct effect of force exerted on the fetal head and the placenta.

Adolescent↗

Catecholamines released from the adrenal medulla exert a compensatory, protective effect at beta 2-adrenoceptors against Paf-induced death in mice.

1. The effects of a number of drugs and experimental conditions, which inhibit or stimulate adrenergic function, were evaluated on platelet-activating factor (Paf)-induced death in conscious mice. 2. Adrenalectomy markedly potentiated Paf toxicity, while guanethidine and reserpine did not. However, reserpine, which produced a virtually complete depletion of catecholamines (CA) in cardiac tissue, was not able to reduce adrenal CA by more than 58%. Drugs which release noradrenaline from the adrenergic nerve terminals, such as tyramine and amphetamine, did not protect mice from Paf toxicity, while drugs or conditions which favour the release of CA from the adrenal medulla, such as urethane and cold-induced stress, did. 3. beta 2- and beta 1 + beta 2-adrenoceptor antagonists (ICI 118551, propranolol and nadolol), but not beta 1-antagonists (atenolol, practolol, metoprolol and CGP 20712 A), potentiated Paf toxicity at low doses; beta 2- and beta 1 + beta 2-agonists (salbutamol, fenoterol and isoprenaline), but not beta 1-agonists (prenalterol and tazolol) were potent inhibitors of Paf toxicity. alpha 1- and alpha 2-adrenoceptor agonists and antagonists did not exert significant effects. Propranolol did not appear to enhance the hypotensive action of Paf in pentobarbitone-anaesthetized mice. 4. It is concluded that manipulation of the release of CA from the adrenal medulla, but not from adrenergic nerves, has profound effects on Paf toxicity in mice. A number of considerations support the hypothesis that bronchoconstriction is a major determinant of Paf-induced death in mice.

Adrenal Cortex Hormones↗

Silent exertional myocardial ischemia in the elderly: a quantitative analysis of anginal perceptual threshold and the influence of autonomic function.

OBJECTIVE: To assess the perception of angina in the elderly and its relationship to autonomic function. DESIGN: Prospective cohort study of patients with exertional ischemia. SETTING: Medical, geriatric and cardiac outpatient clinics in two centers. PARTICIPANTS: All subjects had ischemic heart disease as evidenced by positive treadmill stress tests and, in some, diagnostic angiography and/or documented Q wave infarction. In the first study (I), 37 older patients (range 70-82 years) and 39 younger patients (range 42-59 years) were studied. In a subsequent study (II), a further 49 patients were divided into 2 groups: those with good perception of angina (Anginal Perception Threshold < 15 seconds, group A, 26 patients) and those with no angina despite ischemia (group B, 23 patients). MEASUREMENTS: Anginal perceptual threshold (APT), age, cardiovascular autonomic function, and blood pressure were measured. APT was defined as the time between onset of 1 mm ST depression to the onset of angina during treadmill stress testing. Autonomic function was studied using heart rate ratios before and after the valsalva maneuver, heart rate responses to deep breathing, and heart rate and blood pressure responses to standing. RESULTS: In study I, APT in the older patients was delayed by a median value of 49 seconds [79 (range 15-188) versus 30 (-99 to 97) seconds in the younger patients, P < 0.001]. There was no significant correlation between prolonged APT and autonomic dysfunction when younger and older groups were analyzed independently or together. When, however, the high APT subgroup (APT > 30 seconds) was analyzed separately, there was a significant correlation between APT prolongation and impaired valsalva response (r = -0.4; P < 0.005). In study II, 21 of 23 patients (91.3%) with positive exercise test but with no angina (group B) had at least one abnormal autonomic function test compared with 5 of 26 (19%) patients with good anginal perception (group A). Of note, group A was significantly younger than group B [60 (53-63) years vs 66 (62-70 years, P < 0.001]. CONCLUSION: Elevation of APT in the elderly suggests that warning of critical myocardial ischemia is delayed. Autonomic dysfunction may be one of the underlying mechanisms.

Adult↗

A novel nitric oxide-releasing statin derivative exerts an antiplatelet/antithrombotic activity and inhibits tissue factor expression.

BACKGROUND: NO-releasing statins are new chemical entities, combining HMG-CoA reductase inhibition and slow NO release, that possess stronger anti-inflammatory and antiproliferative activities than the native statins. OBJECTIVE: We evaluated the antithrombotic effects of nitropravastatin (NCX-6550) by assessing its activity on platelet activation and tissue factor (TF) expression by mononuclear cells in vitro and in vivo. METHODS AND RESULTS: In vitro, NCX-6550 inhibited (1) U46619- and collagen-induced platelet aggregation in buffer and plasma; (2) collagen-induced P-selectin expression in whole blood and (3) platelet adhesion to collagen-coated coverslips under high shear stress. These effects were displayed at concentrations of NCX-6550 ranging from 25 to 100 mum, and were totally reverted by the guanylylcyclase inhibitor ODQ (10 microm). Equimolar concentrations of pravastatin had no influence on these parameters of platelet function. LPS- and PMA-induced TF expression by blood mononuclear cells was also inhibited by NCX-6550 (IC50 13 microm), but not by pravastatin, as assessed by functional and immunological assays and by real-time PCR. In a mouse model of platelet pulmonary thromboembolism, induced by the i.v. injection of collagen plus epinephrine, pretreatment with NCX-6550 (24-48 mg kg(-1)) significantly reduced platelet consumption, lung vessel occlusion and mortality. Moreover, nitropravastatin markedly inhibited the generation of procoagulant activity by spleen mononuclear cells and peritoneal macrophages in mice treated with LPS. In these in vivo models too, pravastatin failed to affect platelet activation and monocyte/macrophage procoagulant activity. CONCLUSIONS: Our results show that nitropravastatin exerts strong antithrombotic effects in vitro and in vivo, and may represent an interesting antiatherothrombotic agent for testing in acute coronary syndromes.

Animals↗

The influence exerted by cutaneous ligands in subjects reacting to nickel sulfate alone and in those reacting to more transition metals.

To study the influence exerted by cutaneous ligands in nickel reactions we have evaluated the patch tests responses to 4 aqueous nickel salts (sulfate, chloride, nitrate, acetate) able to form different complexes with different geometry. Two groups of respectively 71 subjects who previously reacted only to nickel sulfate 5% petrolatum (pet) and of 30 subjects who previously reacted to nickel sulfate 5% pet and to at least 1 other transition metal, were simultaneously repatch-tested to 200 microg of Ni++ contained in nickel sulfate in pet and to 47 microg of Ni++ contained in 4 different aqueous nickel salts. Another 2 groups of 25 subjects with the same characteristics were simultaneously repatch tested to 200 microg of Ni++ in pet and to 12 microg of aq Ni++ as in the first 2 groups. Visual score, total score, and mean value of the reactions were utilized in evaluating the degree of the responses. On testing to 200 microg of Ni++ in pet all the subjects were able to give positive responses. Whilst a higher percentage of the responses of 2+ degrees was found in subjects reacting to nickel sulfate 5% pet alone, a higher percentage of responses of 3+ degrees was observed in subjects reacting to more transition metals. On testing to 47 and 12 microg of aqueous Ni++ a large variability of responses to the single salts was observed in all the subjects. However, in subjects reacting to more metals there were either a greater number of multiple responses to 3 or 4 salts or responses stronger than those found in subjects reacting to nickel sulfate alone. Although patch testing cannot give us complete information about the degree of previous exposure, the results arising from the tests seem to demonstrate that the subjects allergic to nickel and other transition metals are more reactive than the subjects allergic only to nickel to the application of the same amounts of Ni++ contained in different salts. When considering the QSAR model, the difference in the sensitizing potential of the metal at the same penetration properties can depend on the possibility of combining with specific ligands. Therefore, it is likely that in subjects reacting to more metals there is a more uniform availability of cutaneous ligands which conditions the formation of complexes more immunogenic. The arising inflammatory reaction in these cases leads to a stronger but less specific response.

Analysis of Variance↗

Histidine-rich glycoprotein exerts antibacterial activity.

Histidine-rich glycoprotein (HRGP), an abundant heparin-binding protein found in plasma and thrombocytes, exerts antibacterial effects against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fluorescence studies and electron microscopy to assess membrane permeation showed that HRGP induces lysis of E. faecalisbacteria in the presence of Zn2+ or at low pH. Heparin blocked binding of the protein to E. faecalis and abolished antibacterial activity. Furthermore, truncated HRGP, devoid of the heparin-binding and histidine-rich domain, was not antibacterial. It has previously been shown that peptides containing consensus heparin-binding sequences (Cardin and Weintraub motifs) are antibacterial. Thus, the peptide (GHHPH)4, derived from the histidine-rich region of HRGP and containing such a heparin-binding motif, was antibacterial for E. faecalis in the presence of Zn2+ or at low pH. The results show a previously undisclosed antibacterial activity of HRGP and suggest that the histidine-rich and heparin-binding domain of HRGP mediates the antibacterial activity of the protein.

Amino Acid Motifs↗

Immune response gene (Ir-SRBC) exerts its effect via macrophages in inbred rats.

In the previous report, strain differences of inbred rats were investigated in the antibody response to sheep erythrocytes (SRBC). A low-responder strain (Fischer rats) produced only IgM antibody, but other high-responder strains switched over from IgM to IgG antibody to SRBC. Pretreatment with incomplete Freund's adjuvant made Fischer rats a high-responder. These results seemed to indicate that there are malfunctions of macrophages, together with T cells, in Fischer rat strain. In this report, strain differences in the phagocytic activity of macrophages were examined using radiolabelled SRBC. High uptake of SRBC by the spleen in the low responder rats, and vice versa, was confirmed in various experimental conditions. Genetic analyses were made of the specific spleen uptake of the radiolabelled SRBC in backcrossed rats. The result clearly showed that the degree of spleen uptake of the radiolabelled SRBC is genetically determined by a single gene and this property itself has a close negative correlation with the ability of each rat to produce haemolysin against SRBC. These results strongly suggest that the Ir-SRBC gene exerts its effect, at least in part, via macrophages. The relationship between the function of the macrophage and the antibody response is discussed.

Animals↗

Activation of sympathetic nerves exerts an inhibitory influence on afferent nerve-induced vasodilation unrelated to vasoconstriction in rat dental pulp.

In order to elucidate a possible influence of the sympathetic nervous system on afferent nerve function, rat mandibular incisors were electrically stimulated and blood flow changes monitored in the incisor pulp of untreated and sympathectomized animals by a laser Doppler flowmeter. Monopolar electrical stimulation of the tooth (200 microA, 5 ms, 40 Hz, 1 s) in normal animals resulted in a transient reduction in pulpal blood flow (PBF) (16% reduction, n = 10) followed by a small but long-lasting increase (11% increase). After administration of phenoxybenzamine or phentolamine (3 mg kg-1, i.v.) the initial dip in PBF was reduced by 59% (P < 0.001) while the subsequent increase was enhanced by 185% (P < 0.001). Similarly, infusion of prazosin (50 micrograms kg-1, i.v.) and idazoxan (0.5 mg kg-1, i.v.) significantly enhanced the increase in PBF by 118 and by 79%, respectively. In chronically sympathectomized animals the increase in PBF was 250% larger than that seen in untreated animals (P < 0.001). This increase in PBF was not further enhanced after alpha-adrenergic blockade. Acute resection of the superior cervical sympathetic ganglion, also resulted in some enhancement (by 56%) of the stimulation-induced increase in PBF (P < 0.01, n = 6). The increase in PBF was unaffected by infusion of timolol (150 micrograms kg-1) and atropine (1 mg kg-1) but was totally abolished by intravenous pre-treatment with capsaicin (1-3 mg kg-1). The present results suggest that activation of sympathetic nerves exerts inhibitory effects on the afferent nerve-induced vasodilation in the rat incisor pulp unrelated to sympathetic vasoconstriction.

Adrenergic alpha-Antagonists↗

Effect of dietary starch, fat, and bicarbonate content on exercise responses and serum creatine kinase activity in equine recurrent exertional rhabdomyolysis.

To determine the effect of dietary starch, bicarbonate, and fat content on metabolic responses and serum creatine kinase (CK) activity in exercising Thoroughbreds with recurrent exertional rhabdomyolysis (RER), 5 RER horses were fed 3 isocaloric diets (28.8 Mcal/d [120.5 MJ/d]) for 3 weeks in a crossover design and exercised for 30 minutes on a treadmill 5 days/wk. On the last day of each diet, an incremental standardized exercise test (SET) was performed. The starch diet contained 40% digestible energy (DE) as starch and 5% as fat: the bicarbonate-starch diet was identical but was supplemented with sodium bicarbonate (4.2% of the pellet): and the fat diet provided 7% DE as starch and 20% as fat. Serum CK activity before the SET was similar among the diets. Serum CK activity (log transformed) after submaximal exercise differed dramatically among the diets and was greatest on the bicarbonate-starch diet (6.51 +/- 1.5) and lowest on the fat diet (5.71 +/- 0.6). Appreciable differences were observed in the severity of RER among individual horses. Postexercise plasma pH, bicarbonate concentration, and lactate concentration did not differ among the diets. Resting heart rates before the SET were markedly lower on the fat diet than on the starch diet. Muscle lactate and glycogen concentrations before and after the SET did not differ markedly among the diets. A high-fat, low-starch diet results in dramatically lower postexercise CK activity in severely affected RER horses than does a low-fat, high-starch diet without measurably altering muscle lactate and glycogen concentrations. Dietary bicarbonate supplementation at the concentration administered in this study did not prevent increased serum CK activity on a high-starch diet.

Animal Nutritional Physiological Phenomena↗

The effect of orthopaedic shoeing on the force exerted by the deep digital flexor tendon on the navicular bone in horses.

This study quantifies both the intended effect of orthopaedic shoeing to decrease the load on the navicular bone and the eventual undesired effects on gait performance. The compressive force exerted by the deep digital flexor tendon on the navicular bone and on the quality of the trot and redistribution of forces over the flexor tendons and the suspensory ligament were studied as a function of orthopaedic shoeing in 12 sound Dutch Warmblood horses. A modified CODA-3 gait analysis system and a force plate were used to quantify objectively the load on the lower limb. The quality of the trot was assessed using the same gait analysis system while the horses were trotting on the treadmill. The effects of shoes with heel wedges and egg-bar shoes were compared to flat shoes and unshod feet. When heel wedges were applied, the maximal force on the navicular bone was reduced by 24% (P<0.05) in comparison with flat shoes. Egg-bar shoes did not reduce the force on the navicular bone, but in unshod feet this force appeared to be 14% lower (P<0.05) compared to flat shoes. Egg-bar shoes cause the horse's trot to be slightly less animated (P<0.05), compared to flat shoes and shoes with heel wedges. It is concluded that shoes with heel wedges reduce the force on the navicular bone as a result of a decreased moment of force at the distal interphalangeal joint in combination with a decreased angle between the deep digital flexor tendon distally and proximally of the navicular bone. Therefore it can be expected that in horses suffering from navicular disease, heel wedges will have the expected beneficial effect on the pressure on the navicular bone, while the effect of egg-bar shoes remains doubtful.

Animals↗

Effect of diet on thoroughbred horses with recurrent exertional rhabdomyolysis performing a standardised exercise test.

Previous studies have associated recurrent exertional rhabdomyolysis (RER) with a diet high in soluble carbohydrate (CHO). The purpose of this study was to investigate the effect of 3 diets on clinical and metabolic parameters in 5 Thoroughbred horses with RER and 3 healthy Thoroughbreds performing a standardised exercise test (SET). Two diets were formulated to meet energy requirements for the amount of exercise being performed in the form of CHO or fat (21.4 Mcal DE/day). The third diet was formulated to provide 135% of the DE of the other 2 diets in the form of an excessive amount of carbohydrate (28.8 Mcal DE/day). Diets were fed in a crossover design for 3 week blocks and then horses performed a near maximal SET. Changes in heart rate (HR), plasma lactate, plasma glucose, total plasma solids, packed cell volume (PCV), muscle lactate and muscle glycogen concentration were measured immediately prior to, during, and 5 min after exercise. Serum creatine kinase (CK) activity was measured prior to and 4 h post SET. A 2-way ANOVA was used to examine the effect of group and dietary treatment. When dietary treatments were compared, horses fed the high-CHO diet had a mean pre-SET PCV and pre-SET HR that was higher than horses fed the fat diet (P = 0.06 and P = 0.07, respectively). Pre-SET heart rates were highest in RER horses consuming the high-CHO diet compared to RER horses consuming the low-CHO and fat diets (P = 0.02). Horses with RER had 4 h post SET CK activity greater than 400 u/l in 7/14 (50%) measurements compared to control horses which had CK activity greater than 400 u/l in 2/7 (29%) measurements. This study did not demonstrate a significant effect of diet on rhabdomyolysis, indicated by CK activity, or on the metabolic response to exercise. However, diet may have a calming effect on Thoroughbred horses with RER as manifested by decreased pre-exercise heart rates and decreased pre-exercise PCV in horses fed the fat diet.

Animals↗

Distribution of pellets in the gastrointestinal tract. The influence on transit time exerted by the density or diameter of pellets.

The influence on transit time exerted by the density or diameter of pellets has been established in six ileostomy subjects. An increase in density from 1.0 to 1.6 significantly increased the average transit time of pellets in the small intestine. The average transit time for the light and heavy pellets being 7 and 25 h respectively. The diameter of pellets is of minor significance. The findings suggest the use of density as a means of modifying the period of absorption of controlled-release pellets.

Adult↗

Evidence that 5-hydroxytryptamine may exert both facilitatory and inhibitory control of electrical field stimulation-evoked contractions in longitudinal muscle taken from the body of guinea-pig stomach.

Electrical field stimulation (FS) of guinea-pig stomach body longitudinal muscle strips caused frequency-related contractions mediated via cholinergic mechanisms. Metoclopramide (10(-8)-10(-5) M), MDL 72222 (10(-9)-10(-7) M) and 5-hydroxytryptophan (5-HTP) (3 X 10(-7)-2.4 X 10(-4) M) enhanced these contractions in all tissues, whereas 5-hydroxytryptamine (5-HT) (3 X 10(-8)-3 X 10(-5) M) enhanced the contractions, but only in approximately 15% of the tissues tested. FS-induced contractions were also enhanced in tissues treated in-vitro with p-chlorophenylalanine (2.5 X 10(-7)-2.5 X 10(-5) M) or monofluoromethyldopa (6 X 10(-7)-10(-4) M) or in tissues taken from animals having received p-chlorophenylalanine or monofluoromethyldopa. It is concluded that cholinergic-mediated contractions of stomach strips are subject to 5-HT modulation in two ways. The predominant action of endogenous 5-HT is to exert an inhibitory tone mediated via a metoclopramide and MDL 72222-sensitive 5-HT neuronal receptor. Exogenously applied 5-HT has little overt action to increase the essentially maximal inhibitory action of endogenous 5-HT, but acts on a 5-HT facilitatory receptor system to enhance contractions. Therefore, the actions of 5-HT agonists and antagonists to modify contractions in stomach strips will reflect the balance between 5-HT inhibitory and facilitatory influences, and the specificity of action of the compounds for the two 5-HT receptor systems.

5-Hydroxytryptophan↗

Opioid pathways exert a tonic restraint in the guinea-pig isolated colon: changes after chronic sympathetic denervation.

We have studied the effects of naloxone on acetylcholine and noradrenaline release in the guinea-pig isolated distal colon, and have assessed the effect of naloxone on electrically-induced contractions of the longitudinal muscle and non-adrenergic, non-cholinergic (NANC) relaxations of the circular muscle coat. Naloxone dose-dependently increased resting and electrically-evoked acetylcholine release and electrically-evoked noradrenaline release. Naloxone was more potent in increasing resting acetylcholine release in colonic specimens obtained after chronic sympathetic denervation. Naloxone (1 microM) did not affect electrically-induced contractions of the longitudinal muscle, while it enhanced NANC relaxations of the circular muscle. The effects observed with naloxone in the present experiments suggest that opioid pathways exert a tonic restraint on neurotransmission in the guinea-pig colon. After suppression of the adrenergic inhibitory tone, the functional relevance of opioid pathways seems to be increased.

Acetylcholine↗

The effects of buspirone on perceived exertion and time to fatigue in man.

Male subjects exercised at 80% maximal rate of O2 uptake (VO2,max) following oral administration of either placebo or the partial 5-HT1A agonist buspirone (45 mg), using a paired design. Ratings of perceived exertion were higher following buspirone and time to volitional fatigue (median and inter-quartile range) fell significantly by approximately a third from 26 min (24-30 min) on placebo to 16 min (11-19 min) following buspirone. Serum prolactin was significantly elevated following buspirone administration, indicating increased hypothalamic 5-HT1A receptor stimulation. There were no significant differences in blood lactate or serum glucose between the trials. This study supports the possible central modulation of exercise tolerance by serotonergic pathways, although a role for dopamine cannot be excluded.

Adult↗

Descending inhibitory influences exerted by the brain stem upon the activities of dorsal horn lamina V cells induced by intra-arterial injection of bradykinin into the limbs.

1. In order to study descending influences of the brain stem upon the transmission of nociceptive messages at the spinal level, the activities of lumbar lamina V dorsal horn cells, induced by intra-arterial injection of brandykinin into the limbs, were recorded in unanaesthetized cats in both decerebrate and temporary spinal states (reversible cold block applied at the thoracic level). 2. In the decerebrate state, the intra-arterial injection of bradykinin had little or no effect. 3. During the reversible spinalization, the effects of bradykinin were revealed or considerably enhanced. As described in a previous study, in the C1-transected cat, three types of effects were encountered: excitatory, inhibiitory and mixed (inhibitory-excitatory). 4. These modifications observed after spinalization were generally associated with a large increase of the spontaneous firing rate. 5. These results emphasize, in the decerebrate cat, the importance of descending inhibitory controls exerted by the brain stem upon the transmission of nonciceptive messages at the spinal cord level.

Action Potentials↗

Do identical activity patterns in fast and slow motor axons exert the same influence on the twitch time of cat skeletal muscle?

1. The fast-twitch flexor digitorum (the lateral head; equivalent to the flexor hallucis longus) and slow-twitch soleus muscles of the cat were denervated, and the two nerves immediately reunited to one or the other muscle. Contraction times of the dually reinnervated muscle were examined 9 weeks post-operatively in response to separate stimulation of its own and the foreign nerve. Over a 5 week period before the terminal experiment, a variety of artificial activity patterns was imposed on the two nerves.2. Following the dual-union operation, the flexor digitorum muscle was preferentially reinnervated by its own nerve. In contrast, the soleus muscle showed no evidence of preferential reinnervation.3. When neural activity was not artificially modified, the dually reinnervated flexor digitorum or soleus muscle showed faster contractions in response to stimulation of the flexor digitorum nerve than to stimulation of the soleus nerve.4. Following a 5 week period in which neural activity was virtually eliminated by cord transection or in which the two nerves were stimulated at the same frequency, the contraction times of the dually reinnervated soleus muscle were the same in response to stimulation of either nerve.5. In contrast, under the experimental conditions described above (cord transection or nerve stimulation), the dually reinnervated flexor digitorum muscle showed a significantly faster contraction in response to stimulation of its own nerve than to stimulation of the soleus nerve.6. It is concluded that, when neural activity is absent or identical in pattern, motoneurones normally innervating the fast- or slow-twitch muscles exert the same influence on contraction times of the soleus muscle.7. The dependence of contraction times of the dually reinnervated flexor digitorum muscle upon the type of the innervating motoneurone may be explained either by selective reinnervation of a particular group of muscle fibres or by different trophic substances emanating from the motoneurones.

Action Potentials↗