PubMed Health⌕ Search

Biomedical subjects

F L Strand

Publications and source records attributed to F L Strand.

At least 37 records · Page 2Linked to original sources
PubMed1988

ACTH 4-9 analog (Org 2766) improves qualitative and quantitative aspects of motor nerve regeneration.

ACTH 1-39 and many of its fragments enhance regeneration of rat peripheral nerve and improve motor unit reorganization. The analog of ACTH 4-9 (Org 2766), with longer-lasting activity and greater biological potency for many parameters, was evaluated for its restorative powers on neuromuscular function following denervation. Org 2766 (10 micrograms/kg/48 hr IP) was administered to rats starting 3 hr after crush denervation of the extensor digitorum longus (EDL) muscle. Contractile strength, motor unit performance under low, optimum and high frequency stimulation, and number and size distribution of motor units of the EDL stimulated through the regenerating peroneal nerve were compared to saline-treated controls. Muscles of parallel animal groups were stimulated directly in vitro. Contractile strength and motor unit performance during high frequency stimulation were significantly improved by Org 2766 treatment at both 7 and 11 days after crush denervation. Org 2766 improves motor unit reformation both qualitatively (more small motor units that are highly resistant to fatigue) and quantitatively (stronger motor units). This peptide does not affect muscle contractile components. Prolonged treatment (21 days) with Org 2766 has a negative effect on motor unit performance, indicating that it exerts its favorable effects early in regeneration and exposure to this peptide should be limited to this period.

Adrenocorticotropic Hormone↗
PubMed1988

Maturational changes in neonatal rat motor system with early postnatal administration of nicotine.

Experiments were designed to assess the effects of chronic maximum 'smoking dose' nicotine administration on neonatal motor behavior and neuromuscular structural maturation. Thus, Sprague-Dawley rat neonates received daily subcutaneous injections of nicotine (0.05 mg/kg/day) from postnatal days 1 to 14. Motor behavior (ambulations, stop and go movements) was not affected, but a marked increase in grasping duration resulted, indicating increased neuromuscular maturation. Concomitantly, neuromuscular morphological and dynamic contractile changes were observed in the in situ extensor digitorum longus (EDL) muscle. The EDL muscle showed accelerated morphological dimensions of the endplate at postnatal day 7 and a more rapid twitch at 2 weeks of age. The results suggest that this maximum 'smoking dose' of nicotine induces time-dependent maturational changes in the neuromuscular model.

Animals↗
PubMed1985

ACTH/MSH 4-10 improves motor unit reorganization during peripheral nerve regeneration in the rat.

ACTH/MSH 4-10 administration (10 micrograms/48 hr IP for 7 days) enhances neuromuscular activity following crush denervation of rat extensor digitorum longus muscle. The number of regenerated functional motor units is greater in peptide treated rats than in saline treated denervated controls. Selective activation of responding motor units indicates that ACTH/MSH 4-10 preferentially accelerates the reformation and stabilization of small size motor units. These observed effects may be beneficial since they contribute to the early reestablishment of more organized motor units, thereby restoring fine control of motor functions, in contrast to the disorderly reorganization of untreated regenerating systems. Possible mechanisms of peptide action (neurotransmitter synthesis and release, excitability changes, etc.) are discussed.

Adrenocorticotropic Hormone↗
PubMed1985

ACTH peptides as organizers of neuronal patterns in development: maturation of the rat neuromuscular junction as seen by scanning electron microscopy.

SEM was used to visualize the normal postnatal development of the neonatal rat neuromuscular junction (nmj). Maturational changes evoked by ACTH/MSH 4-10 (10 micrograms/kg/day IP) or ACTH/MSH 4-9 (Org 2766) (0.01 microgram/kg/day IP) were compared to controls and to pups treated with nicotine during prenatal and postnatal life, or only during the gestation period. Pregnant females received 0.25 mg/kg 2X daily IP; neonates 0.05 mg/kg/day SC. The Desaki and Uehara and Fahim et al. methods revealed the nmj on the extensor digitorum muscle to be covered by a delicate drapery of postjunctional folds that surround the immature endplate region. By the second week of postnatal life, these folds become more complex and cover a larger area. Upon maturation the folds descend and invaginate into the muscle fiber. Peptide treatment with either ACTH/MSH 4-10 or ACTH/MSH 4-9 accelerates maturation of the endplate as demonstrated by the increased convolutions of the folds. Similar effects follow nicotine administration. The observed changes in morphology of the developing nmj subjected to nicotine may be mediated through nicotine-evoked ACTH release.

Adrenocorticotropic Hormone↗
PubMed1985

ACTH neuromodulation of the developing motor system and neonatal learning in the rat.

ACTH peptides influence the developing nervous system during the first three weeks of life in the rat. ACTH 4-10 and Org 2766 (10.0 micrograms/kg) accelerate the expression of motor hyperactivity usually exhibited in 15-day old normal animals, with ACTH 4-10 increasing the force of extensor digitorum longus muscle contraction amplitude. Following cold stress and peptide treatment, rate changes in motor activity from one age to the next are dramatically enhanced, with vertical activity being exhibited at an earlier age than controls. Grasping ability is similarly enhanced in 13-day old ACTH 4-10-treated animals. The retention of a T-maze learning paradigm is significantly enhanced in 16-day old ACTH 4-10 (10.0 micrograms/kg)-treated and Org 2766 (0.01 micrograms/kg)-treated animals, with these animals running the maze significantly faster than controls. Peptide treatment appears to reverse the apparent turning preference in the maze during extinction. It is suggested that ACTH peptides modulate the organization of the nervous system and facilitate neurotransmission, and may act on dopaminergic and cholinergic neurotransmitter systems. Motor behavior seems to reflect underlying neural substrates that are integrated to produce the overt behavior of the organism.

Adrenocorticotropic Hormone↗
PubMed1985

Development and regeneration of motor systems under the influence of ACTH peptides.

ACTH peptides exert quantitative and qualitative influences on the formation and maturation of motor units in developing and regenerating neuromuscular systems. ACTH 4-10, administered daily (10 micrograms/kg. s.c.) from the day of birth, accelerated the rate at which muscle strength developed in the immature rat, the effect of this peptide being most marked in animals 11-15 days old. A similar increase in grasping time occurred in ACTH 4-10 treated animals, indicating that the peptide affects neuronal maturation at a time in development when organization and maturation of the neuromuscular system is most active. The synthetic analogue of ACTH 4-9 (Org 2766), administered in the same dosage, had little effect on these parameters, indicating a differential sensitivity to these similar peptides. Elevated circulating titers of ACTH, whether exogenous (0.2 U ACTH 1-39 IP daily), or endogenous (adrenalectomy), stimulated the formation of more functional motor units, as indicated by increased amplitude of muscle action potentials and tetanic tension following nerve stimulation. ACTH appears to favor the recovery of high threshold, small-size motor units. Fine control of muscle function in peptide-treated animals is partially restored, as indicated by the return of stepwise recruitment to an extent not seen in the reinnervated, saline-treated controls.

Adrenocorticotropic Hormone↗
PubMed1981

Neurotropic action of MSH/ACTH 4-10 on neuromuscular function in hypophysectomized rats.

These studies were designed to determine whether the previously demonstrated [24] enhancement of neuromuscular function by MSH/ACTH 4-10 is due to peptide action on the neurogenic and/or myogenic elements involved. The nerve muscle unit studied incorporated the sciatic nerve and its branches, and the extensors digitorum longus and brevis in the hypophysectomized rat, in situ. Parameters investigated included muscle action potentials (MAP) and muscle contractions (MC) during 30 min of stimulation (supramaximal, 10/sec; 0.05 msec duration). Resting membrane potentials and miniature endplate potential (mepp) characteristics were investigated in situ at neuromuscular junctions in the extensor digitorum brevis. Hypophysectomy results in markedly deleterious changes in neuromuscular function which can be partially alleviated by the administration of ACTH 4-10 (0.01 microgram/kg). This dosage increases MAP and MC amplitudes and reduces fatigue. Higher dosages (1.0 microgram/kg) have a depressing effect on these parameters. The facilitatory actions of ACTH 4-10 are abolished when the muscle is stimulated directly or stimulated through the peripheral stump of the cut nerve. ACTH 4-10 increases mepp frequency (a presynaptic event) but does not affect postsynaptic characteristics as measured by the resting membrane potential. These results indicate that MSH/ACTH 4-10 influences skeletal muscle function through a neurotropic action mediated by spinal motoneurons. Changes in the central excitatory state of higher motor centers are possibly involved.

Adrenocorticotropic Hormone↗
PubMed1981

Neuromuscular response of the immature rat of ACTH/MSH 4--10.

The adrenocorticotropin fragment ACTH/MSH 4--10 (0.1 ug/kg IP) effectively modulates the neuromuscular responses of 9 to 15 day old rats. Muscle (extensor digitorum longus) contraction amplitude is increased, fatigue is delayed and muscle half-relaxation time is shortened during 20 min of continuous in situ stimulation of a branch of the deep peroneal nerve (square wave shocks 10 Hz, duration 0.5 msec, strength supermaximal). No effect on contraction time is seen. There is no facilitation or change in any contraction parameter in rats older than two weeks (16 to 40 days) indicating that these older animals, like normal adult rats, are unaffected by the peptide. Immature rats, however, are even more sensitive than hypophysectomized adult rats [29] to the ameliorative action of ACTH/MSH 4-10. This early sensitivity to ACTH/MSH 4--10 corresponds to important developmental changes occurring in nerve and muscle during the most critical period in postnatal development, the first two weeks.

Adrenocorticotropic Hormone↗
PubMed1980

ACTH accelerates recovery of neuromuscular function following crushing of peripheral nerve.

Adrenocorticotropin (ACTH)-treated adrenalectomized rats subjected to crush denervation recover sensation and functional movement sooner than saline-treated rats. Axonal regeneration is accelerated, the number of large endplates and the frequency of preterminal branching are increased. ACTH has no effect on either intact or denervated muscles. The ameliorative action of ACTH during regeneration is apparently neurogenic and independent of corticoids.

Adrenalectomy↗
PubMed1977

Changes in muscle action potentials of patients with diseases of motor units following the infusion of a peptide fragment of ACTH.

The polypeptides ACTH and ATCH4-10 (OI 63) witha sequence of amino acids H-Met-Glu-His-Phe-Arg-Trp-Gly-OH, have similar stimulating effects on motor units in lower mammals. Their actions differ primarily in that ACTH4-10 is not corticotropic. Since the corticotropic action of ACTH frequently presents a problem during its clinical use in treatment of motor unit diseases, the action of ACTH4-10 was studied in two patients with muscular atrophy. Prior to administration of ACTH4-10, stimulation of M. oppenens pollicis through the median nerve evoked muscle action potentials in both patients which progressively declined in amplitude. This decline was not observed subsequent to the infuscion of ACTH4-10 (3, 6 and 15 mg). The effect lasted partially in excess of at least 2 h. It is suggested that ACTH4-10 produces this effect by direct action on a peripheral component of the motor unit and/or indirectly by an action on the central nervous system.

Action Potentials↗
PubMed1976

Peptide enhancement of neuromuscular function: animal and clinical studies.

Evidence is presented for an extra-adrenal effect of ACTH and ACTH analogs on muscle action potentials (APs), contractions and fatigue in in situ experiments. ACTH, alphaMSH, betaMSH and ACTH 4-10 increase the amplitude of APs and contractions and decrease fatigue in intact, hypophysectomized and in adrenalectomized rats, subjected to repetitive indirect stimulation (supermaximal strength, 5/sec or 10/sec for 30 min). Elevation of endogenous ACTH resulting from adrenalectomy or cold stress, or both, has the same effect as ACTH administration. ACTH peptides are most effective in depressed physiological conditions e.g. following hypophysectomy. As the effect of ACTH 4-10 is abolished after section of the motor nerve, it is inferred that this peptide may affect central motor neurons. Preliminary observations from clinical studies with ACTH 4-10 in patients with muscle disease, in whom a pathological decline in amplitude of a short series of evoked muscle APs was prevented by peptide administration, also indicate a possible action of this peptide on central nervous system neurons.

Action Potentials↗