Biomedical subjects

K E Misulis

Publications and source records attributed to K E Misulis.

10 recordsLinked to original sources

PubMed1991

Prevention of diisopropylphosphorofluoridate-induced myopathy by botulinum toxin type A blockage of quantal release of acetylcholine.

Botulinum toxin type A (BTx), which blocks quantal and partially reduces spontaneous nonquantal acetylcholine (ACh) release at neuromuscular junctions, was tested for its possible attenuating effect on diisopropylphosphorofluoridate (DFP)-induced muscle lesions. The extent of muscle lesion in extensor digitorum longus and soleus muscle of DFP injected rats with and without BTx pretreatment was evaluated using light and electron microscopic procedures. In parallel experiments, acetylcholinesterase (AChE) activity was measured and the functional state of muscles in experimental groups was determined by electrophysiological methods. The results show that pretreatment with BTx almost completely protects the muscles from DFP-induced spontaneous activity and lesions in spite of critically inhibited synaptic AChE. These results are consistent with the conclusion that the effect is not mediated by direct action of organophosphate on muscle, but by the accumulation of ACh resulting in muscle hyperactivity. Therefore, it is concluded that in conditions of acutely inhibited synaptic AChE, the quantal release of ACh is essential for lesion induction, whereas the spontaneous nonquantal ACh release, which is only partially affected in BTx-blocked nerve endings, seems not to be involved.

Acetylcholine↗

PubMed1989

Activity dependent characteristics of fast and slow muscle: biochemical and histochemical considerations.

The effects of denervation and hindlimb suspension induced disuse on concentrations of ATP, phosphocreatine (PC), and fiber type profile were investigated in slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles. The results show that the soleus and EDL muscles differ in their dependency on loadbearing as a stimulus for maintaining normal energy metabolism and the biochemical and morphological characteristics of muscle fibers. As determined by R-P methodology, suspension reduced ATP and PC concentrations of the soleus to 26% and 56%, respectively, while, in EDL only, PC is reduced to 71% of control with no change in ATP. Both muscles, however, show identical losses in ATP and PC following denervation. The energy charge, an indicator of Pi availability in muscle was reduced significantly in both denervated muscle to 82% and 85% in soleus and EDL, respectively. No significant reduction of the energy charge was seen in the muscles from suspended rats. Thus, in parallel with the indirect regulation through muscle loadbearing, the nerve can effectively modulate the levels of high-energy phosphates more directly by some regulatory mechanisms independent of muscle type. Denervation and suspension disuse increased the proportion of type 2 fibers in the soleus with a concomitant decrease in type 1 fibers and a relative rise in the number of very small diameter fibers. The EDL showed only variation in fiber size.

Adenosine Diphosphate↗

PubMed1989

Basic electronics for clinical neurophysiology.

This article reviews the basic electronics that are important to clinical neurophysiology. It is divided into six sections: basic principles of electronics; filters; transistors and amplifiers; displays; electrodes and the electrode-amplifier interface; and electrical safety. In addition, at the end of the review is a brief electronics glossary (Appendix A) and an annotated bibliography (Appendix B) to guide further reading.

Electric Conductivity↗

PubMed1988

Prevention of diisopropylphosphorofluoridate (DFP)-induced skeletal muscle fiber lesions in rat.

The objective of the present investigation was to assess the comparative efficacy of prophylactic treatment with d-tubocurarine (d-TC) (0.075 mg/kg), atropine sulfate (16 mg/kg), and atropine methylnitrate (16 mg/kg), employed singly or in combination against the diisopropylphosphorofluoridate (DFP)-induced myopathy in rat. DFP (1.5 mg/kg, s.c.) produced signs of cholinergic toxicity with predominantly peripheral involvement manifest as severe muscle fasciculations beginning within 5-7 min and persisting in excess of 4-6 h. Maximal muscle fiber necrosis was observed within 24 h. Rats were protected against the apparent behavioural and morphological changes as well as electrophysiological signs of neuromuscular toxicity by all pretreatment agents. Combined pretreatment with d-TC (0.075 mg/kg, s.c.) and atropine methylnitrate (16 mg/kg, s.c.) was found to be most effective in attenuating DFP-induced muscle fiber necrosis as evidenced by complete absence of lesions and the prevention of DFP-induced hyperactivity in nerve and muscle. Significant protection was afforded by all pretreatment agents when given alone. It is suggested that the pretreatment agents act presynaptically by preventing drug-induced backfiring and muscle fasciculations possibly by reducing the release of acetylcholine (ACh). The protective drugs in the concentrations used had no significant effect on the normal characteristics of conduction and transmission.

Action Potentials↗

PubMed1988

Effects of phenytoin, ketamine, and atropine methyl nitrate in preventing neuromuscular toxicity of acetylcholinesterase inhibitors soman and diisopropylphosphorofluoridate.

Toxic manifestations of acetylcholinesterase inhibitors (AChE-I) include muscle twitching and muscle fiber necrosis, in addition to muscarinic manifestations of acetylcholine excess. The AChE-Is pinacolyl methylphosphonofluoridate (soman) or diisopropylphosphorofluoridate (DFP) were administered to rats to produce spontaneous muscle fiber discharges. Soman produced discharges that arose primarily from the central nervous system (CNS), while those due to DFP were generated from the peripheral nerves as well as the CNS. Three drugs were tested for their potential to reduce muscle fiber discharges: atropine methyl nitrate (AMN), ketamine, and phenytoin. Ketamine caused a significant decrease in discharges of CNS origin, while AMN and phenytoin had no effect. For muscle fiber discharges of peripheral origin, all three drugs produced a significant drop in muscle fiber discharges, but phenytoin showed slightly more efficacy than the others. AChE-I-induced muscle hyperactivity arises from actions on the CNS and on the peripheral nerve in varying proportions for different AChE-Is. Treatment for the toxicity of AChE-Is on muscle may be accomplished by administering drugs with distinctive pharmacological actions at target sites in the CNS and peripheral nervous system (PNS) where AChE-Is exert their effects. By attenuating the effects of AChE-Is at specific CNS or PNS sites, the neuromuscular toxicity can be reduced in a manner specific to the characteristic sites of toxicity of each AChE-I.

Animals↗

PubMed1987

Differences in central and peripheral neural actions between soman and diisopropyl fluorophosphate, organophosphorus inhibitors of acetylcholinesterase.

Toxic doses of acetylcholinesterase (AChE) inhibitors produce prominent motor symptoms (fasciculations, fibrillations, and body tremors) and muscle fiber necrosis. The severity and quality of motor symptoms and fiber necrosis depend upon the specific AChE inhibitor. To examine the importance of nerve and muscle activity in producing muscle necrosis, we recorded electromyographic activity from normal and acutely denervated rat gastrocnemius muscle following administration of the organophosphorus AChE inhibitors soman and diisopropyl fluorophosphate (DFP). The motor symptoms induced on the denervated side represented activity originating at the nerve terminal while those of the contralateral nondenervated muscle represented the sum of peripheral plus central descending activity. The results indicate that soman and DFP produce different responses. At nonlethal toxic doses, the majority of motor symptoms induced by soman is due to impulses descending from the central nervous system, and a proportion of these symptoms are epileptiform activity. This activity is not generated at spinal levels. In contrast, DFP produces motor symptoms mainly by peripheral action that is dependent on a functioning nerve terminal. At lethal doses, both agents have central and peripheral effects. Different patterns of electrical activity are associated with each of the motor symptoms. We found that muscle fiber necrosis correlates best with peripherally generated high-frequency repetitive discharges.

Acetylcholinesterase↗

PubMed1987

Cerebellar metastases: diagnostic and management considerations.

Prompted by several unsatisfactory outcomes, we reviewed the records of 59 patients with cerebellar metastases (26 solitary) with respect to clinical presentation, diagnosis, and natural history. Eighty-seven percent of patients initially complained of headache, gait disturbance, and/or dizziness. At time of diagnosis, 92% of patients with solitary cerebellar metastases and 74% of the overall series complained of headache and/or difficulty walking. In three of four cases, magnetic resonance imaging (MRI) was superior to x-ray computed tomography (CT) in detecting the cerebellar lesions. Several patients acutely deteriorated during evaluation or at the initiation of radiation therapy. We conclude that a cancer patient presenting with headache and gait difficulty with or without nausea/vomiting and dizziness should promptly undergo head CT scanning, and that MRI is useful even if CT is negative. In addition, we recommend that patients with documented cerebellar metastases receive high-dose glucocorticoid therapy for 48 to 72 hours before beginning radiation therapy. The presence of symptomatic hydrocephalus or failure to respond to glucocorticoids initially are particularly ominous features that may be best managed by early neurosurgical consultation before beginning radiation therapy.

Adult↗

PubMed1985

Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension-induced disuse.

Muscle disuse-induced changes in the cholinergic system of sciatic nerve, slow-twitch soleus (SOL), and fast-twitch extensor digitorum longus (EDL) muscles were studied in rats. Rats with hind limbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase in sciatic nerve (38%), in the SOL (108%), and in the EDL (67%). Acetylcholinesterase (AChE) activity in the SOL increased 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant (P greater than 0.05) changes in the activity and molecular forms pattern of AChE were seen in the EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of [3H]acetylcholine was increased in both muscles. When measured after 3 weeks of hind limb suspension the normal distribution of type I fibers in the SOL (87%) was reduced (to 58%) and a corresponding increase in types IIa and IIb fibers occurred. In the EDL no significant change in fiber proportion was observed. Muscle activity, such as loadbearing, appeared to have a greater controlling influence on the characteristics of the slow-twitch SOL muscle than on the fast-twitch EDL muscle.

Acetylcholinesterase↗

PubMed1985

Is fast fiber innervation responsible for increased acetylcholinesterase activity in reinnervating soleus muscles?

During reinnervation of the completely denervated rat hind limb we observed previously a temporary overproduction of acetylcholinesterases in the soleus but not in the extensor digitorum longus muscle. In the present study, we investigated whether the predominantly slow soleus, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the extensor digitorum longus. Local denervation of the rat soleus was carried out to eliminate reinnervation by axons destined for other muscles. This produced an overshoot in AChE activity that was qualitatively similar to that observed with high sciatic crush. Local denervation of the soleus in the guinea pig was done because this muscle is composed solely of slow (type I) fibers, thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the soleus. We concluded that the neural control of AChE is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle. How these neural influences are translated into muscle synthesis and degradation remains unknown.

Acetylcholinesterase↗

PubMedDate not supplied

Genetic forms of myasthenia gravis.

Myasthenia in newborns and infants is usually genetic and not mediated by antibodies to the acetylcholine receptor. Several different pre- and postsynaptic defects are responsible for early-onset myasthenia. This review presents a classification of these syndromes based upon knowledge of their pathophysiologic bases and a plan for the evaluation of new patients.

Humans↗