Serial elongation, derotation and flexion (EDF) casting under general anesthesia and neuromuscular blocking drugs improve outcome in patients with juvenile scoliosis: preliminary results.

PubMed

Canavese, Federico; Botnari, Alexei; Dimeglio, Alain; Samba, Antoine; Pereira, Bruno; Gerst, Adeline; Granier, Marie; Rousset, Marie; Dubousset, Jean

2016-02-01

Juvenile scoliosis (JS), among different types of spinal deformity, remains still a challenge for orthopedic surgeons. Elongation, derotation and flexion (EDF) casting technique is a custom-made thoracolumbar cast based on a three-dimensional correction concept. The primary objective of the present study was to measure changes on plain radiographs of patients with JS treated with EDF plaster technique. The second aim was to evaluate the effectiveness of the EDF plaster technique realized under general anesthesia (GA) and neuromuscular blocking drugs, i.e. curare, on the radiological curve correction. A retrospective comparative case series study was performed in which were included forty-four skeletally immature patients. Three patient groups were selected. Group 1: EDF cast applied with patients awaken and no anesthesia; Group 2: EDF cast applied under GA without neuromuscular blocking drugs; Group 3: EDF cast applied under GA with neuromuscular blocking drugs. All the patients were treated with two serial EDF casts by 2 months and a half each. All measurements were taken from the radiographic exams. Cobb's angle; RVAD and Nash and Moe grade of rotation were assessed before and after applying the cast. Thirty-four (77.3 %) patients were followed up at least 24 months after removal of last EDF cast. Eighteen patients (3 males, 15 females) were included in Group 1, 12 (2 males, 10 females) in Group 2 and 14 (5 males, 9 females) in Group 3. Serial EDF casting was more effective at initial curve reduction and in preventing curve progression when applied under GA with neuromuscular blocking drugs, i.e. curare. RVAD and Nash and Moe score improved significantly in all groups of patients treated according to principles of EDF technique. During follow-up period, six patients required surgery in Group 1 (6/18; 33.3 %), 3 patients required surgery in Group 2 (3/12; 25 %) and 2 patients underwent surgery in Group 3 (2/14; 15 %). Preliminary results show EDF casting is effective in controlling the curve in both frontal (Cobb's angle) and transverse plane (rib vertebral angle and apical vertebral rotation degree).

[Neurologic-psychiatric follow-up studies of reanimated tetanus patients (author's transl)].

PubMed

Samtleben, T

1977-01-21

During a study of sequela of intensive care therapy eight patients with longterm respirator treatment for severe tetanus infection were studied by neurologic-psychiatric examination two years or more after discharge from the hospital. Two out of four patients with permanent damage suffered from ankylosis of the hip joint caused by myositis ossificans. One patient showed hyperaesthetic-emotional syndrom and IQ-reduction caused by cardiac arrest. Two further patients were resuscitated from cardiac arrest without persisting psycho-physiological injury. A 70 year old man suffered from cardiopulmonary injury, lack of initiative and fatigability. None of the patients complained of depressing memories and all emphazised their pleasure of being alive. The permanent damage fation and not to the tetanus toxin per se. Improved techniques for tetanus patients on curare and artificial respiration may result in better therapeutical results in the future.

Intérêt de l’algorithme rocuronium - sugammadex dans la laryngoscopie directe en suspension

PubMed Central

El jaouhari, Sidi Driss; Meziane, Mohamed; Ahtil, Redouane; Bensghir, Mustapha; Haimeur, Charki

2017-01-01

La laryngoscopie directe en suspension est un geste chirurgical diagnostique et/ou thérapeutique des lésions endo-laryngées. Sa gestion anesthésique est compliquée. Différentes techniques anesthésiques peuvent être proposées. Malgré les contraintes, les curares gardent tout leur intérêt. L’association rocuronium et sugammadex est envisageable, elle permet une inversion rapide du bloc neuromusculaire profond et par conséquent une réduction de la morbidité postopératoire. Nous rapportons un cas d’une laryngoscopie directe en suspension réalisée sous anesthésie générale dont l’utilisation de l’association rocuronium-sugammadex a permis une facilité du geste chirurgicale, une sécurité pour le patient et un confort pour l’anesthésiste. PMID:28690746

Responsiveness of rat fetuses to sibling motor activity: Communication in utero?

PubMed

Brumley, Michele R; Hoagland, Riana; Truong, Melissa; Robinson, Scott R

2018-04-01

Previous research has revealed that fetuses detect and respond to extrauterine stimuli such as maternal movement and speech, but little attention has been cast on how fetuses may directly influence and respond to each other in the womb. This study investigated whether motor activity of E20 rat fetuses influenced the behavior of siblings in utero. Three experiments showed that; (a) contiguous siblings expressed a higher frequency of synchronized movement than noncontiguous siblings; (b) fetuses that lay between two siblings immobilized with curare showed less movement relative to fetuses between saline or uninjected controls; and (c) fetuses between two siblings behaviorally activated by the opioid agonist U50,488 also showed less activity and specific behavioral changes compared to controls. Our findings suggest that rat fetuses are directly impacted by sibling motor activity, and thus that a rudimentary form of communication between siblings may influence the development of fetuses in utero. © 2018 Wiley Periodicals, Inc.

Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

NASA Astrophysics Data System (ADS)

Maertens, Gaetan; L'homme, Chloe; Canesi, Sylvain

2014-12-01

We present a review of natural product syntheses accomplished in our laboratory during the last five years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the “aromatic ring umpolung” concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol), a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor), acetylaspidoalbidine (an antitumor agent), fortucine (antiviral and antitumor), erysotramidine (curare-like effect), platensimycin (an antibiotic), and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis). These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy

PubMed Central

Kim, Ji Eun; Chun, Hea Rim

2017-01-01

Abstract Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. Clinical features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD. PMID:28353578

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy: A case Report.

PubMed

Kim, Ji Eun; Chun, Hea Rim

2017-03-01

Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.

Imaging synaptic vesicle recycling by staining and destaining vesicles with FM dyes.

PubMed

Hoopmann, Peer; Rizzoli, Silvio O; Betz, William J

2012-01-01

The synaptic vesicle is the essential organelle of the synapse. Many approaches for studying synaptic vesicle recycling have been devised, one of which, the styryl (FM) dye, is well suited for this purpose. FM dyes reversibly stain, but do not permeate, membranes; hence they can specifically label membrane-bound organelles. Their quantum yield is drastically higher when bound to membranes than when in aqueous solution. This protocol describes the imaging of synaptic vesicle recycling by staining and destaining vesicles with FM dyes. Nerve terminals are stimulated (electrically or by depolarization with high K(+)) in the presence of dye, their vesicles are then allowed to recycle, and finally dye is washed from the chamber. In neuromuscular junction (NMJ) preparations, movements of the muscle must be inhibited if imaging during stimulation is desired (e.g., by application of curare, a potent acetylcholine receptor inhibitor). The main characteristics of FM dyes are also reviewed here, as are recent FM dye monitoring techniques that have been used to investigate the kinetics of synaptic vesicle fusion.

[Maxillo-facial surgery in skeletal Class II: repercussions on the temporo-mandibular joints].

PubMed

Manière-Ezvan, Armelle; Savoldelli, Charles; Busson, Floriant; Oueiss, Arlette; Orthlieb, Jean-Daniel

2016-03-01

These interventions usually aimed at the correction of the skeletal discrepancy by mandibular retrognatism with an advancement of the distal portion of the mandible after mandibular osteotomy. The position of the condyle is determined during the osteosynthesis with miniplates. Condyles are set back in relation with the supine position of the patient and the weakness of his (her) curarized muscle. All studies show that surgery of mandibular advancement causes a lateral, torque and backward movement of the condyles, all harmful to the condyles. Factors that predispose to condylar resorption are "the patient": a woman, young (between 15 and 40), high mandibular angle, with a history of temporo-mandibular disorders and surgical overload applied to the condyles. What are the possible solutions to avoid failures? Patient preparation before surgery and surgery simulation with an articulator, condylar position control during surgery, working with surgeons to achieve a condylar portion stabilization system (with the CAD), quickly set up a mobilization of the mandible by physiotherapy. © EDP Sciences, SFODF, 2016.

Agrin-LRP4-MuSK signaling as a therapeutic target for myasthenia gravis and other neuromuscular disorders.

PubMed

Ohno, Kinji; Ohkawara, Bisei; Ito, Mikako

2017-10-01

Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Isaacs' syndrome, congenital myasthenic syndromes, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Except for sarcopenia, all are orphan diseases. In addition, the NMJ signal transduction is impaired by tetanus, botulinum, curare, α-bungarotoxin, conotoxins, organophosphate, sarin, VX, and soman to name a few. Areas covered: This review covers the agrin-LRP4-MuSK signaling pathway, which drives clustering of acetylcholine receptors (AChRs) and ensures efficient signal transduction at the NMJ. We also address diseases caused by autoantibodies against the NMJ molecules and by germline mutations in genes encoding the NMJ molecules. Expert opinion: Representative small compounds to treat the defective NMJ signal transduction are cholinesterase inhibitors, which exert their effects by increasing the amount of acetylcholine at the synaptic space. Another possible therapeutic strategy to enhance the NMJ signal transduction is to increase the number of AChRs, but no currently available drug has this functionality.

Ancient medical texts, modern reading problems.

PubMed

Rosa, Maria Carlota

2006-12-05

The word tradition has a very specific meaning in linguistics: the passing down of a text, which may have been completed or corrected by different copyists at different times, when the concept of authorship was not the same as it is today. When reading an ancient text the word tradition must be in the reader's mind. To discuss one of the problems an ancient text poses to its modern readers, this work deals with one of the first printed medical texts in Portuguese, the Regimento proueytoso contra ha pestenença, and draws a parallel between it and two related texts, A moche profitable treatise against the pestilence, and the Recopilaçam das cousas que conuem guardar se no modo de preseruar à Cidade de Lixboa E os sãos, & curar os que esteuerem enfermos de Peste. The problems which arise out of the textual structure of those books show how difficult is to establish a tradition of another type, the medical tradition. The linguistic study of the innumerable medieval plague treatises may throw light on the continuities and on the disruptions of the so-called hippocratic-galenical medical tradition.

Pharmacological properties of pempidine (1:2:2:6:6-pentamethylpiperidine), a new ganglion-blocking compound

PubMed Central

Corne, S. J.; Edge, N. D.

1958-01-01

Pempidine (1:2:2:6:6-pentamethylpiperidine) is a long-acting ganglion-blocking compound which is effective by mouth. By intravenous injection it has a similar potency to hexamethonium on the preganglionically stimulated nictitating membrane of the cat. The compound blocks the effects of intravenous nicotine and of peripheral vagal stimulation on the blood pressure; it also causes dilatation of the pupil after removal of the sympathetic innervation. On the guinea-pig ileum, the predominant effect of the compound is to inhibit nicotine contractions. Pempidine is well absorbed from the gastro-intestinal tract as judged by (a) the low ratio (6.9) of oral to intravenous toxicities, (b) the rapid development of mydriasis in mice after oral administration of small doses, and (c) the rapid onset of hypotension when the compound is injected directly into the duodenum of anaesthetized cats. Other actions include neuromuscular paralysis of curare-like type when large doses of the compound are injected intravenously and central effects such as tremors which occur with near toxic doses. In cats with a low blood pressure, large intravenous doses have a slight pressor action. PMID:13584741

Acetylcholine and lobster sensory neurones

PubMed Central

Barker, David L.; Herbert, Edward; Hildebrand, John G.; Kravitz, Edward A.

1972-01-01

Experiments are presented in support of the hypothesis that acetylcholine functions as a sensory transmitter in the lobster nervous system. 1. Several different peripheral sensory structures incorporate radioactive choline into acetylcholine. The preparation most enriched in sensory as opposed to other nervous elements (the antennular sense organs of the distal outer flagellum) does not incorporate significant amounts of glutamate, tyrosine or tryptophan into any of the other major transmitter candidates. 2. There is a parallel between the distribution of the enzyme choline acetyltransferase and the proportion of sensory fibres in nervous tissue from many parts of the lobster nervous system. 3. Isolated sensory axons contain at least 500 times as much choline acetyltransferase per cm of axon as do efferent excitatory and inhibitory fibres. 4. Abdominal ganglia and root stumps show a decline in the rate of incorporation of choline into acetylcholine 2 to 8 weeks after severing the first and second roots bilaterally (leaving the connectives and third roots intact). Extracts of the root stumps exhibit a significantly lower level of choline acetyltransferase 2 weeks after this operation. 5. Curare and atropine partially block an identified sensory synapse in the lobster abdominal ganglion. ImagesText-fig. 4Text-fig. 5Plate 1 PMID:4343316

In vitro pharmacologic characterization of a cholinergic receptor on outer hair cells.

PubMed

Erostegui, C; Norris, C H; Bobbin, R P

1994-04-01

Acetylcholine (ACh) is the major neurotransmitter released from the efferent fibers in the cochlea onto the outer hair cells (OHCs). The type of ACh receptor on OHCs and the events subsequent to receptor activation are unclear. Therefore we studied the effect of agonists and antagonists of the ACh receptor on isolated OHCs from the guinea pig. OHCs were recorded from in whole cell voltage and current clamp configuration. ACh induced an increase in outward K+ current (IACh) which hyperpolarized the OHCs. No desensitization to ACh application was observed. Cs+ replaced K+ in carrying the IACh. The IACh is Ca(2+)-dependent, time and voltage sensitive, and different from the IKCa induced by depolarization of the membrane potential. When tested at 100 microM, several agonists also induced outward current responses (acetylcholine > suberyldicholine > or = carbachol > DMPP) whereas nicotine, cytisine and muscarine did not. The IACh response to 10 microM ACh was blocked by low concentrations of traditional and non-traditional-nicotinic antagonists (strychnine > curare > bicuculline > alpha-bungarotoxin > thimethaphan) and by higher concentrations of muscarinic antagonists (atropine > 4-DAMP > AF-DX 116 > pirenzepine). Pharmacologically, the ACh receptor on OHCs is nicotinic.

Hemlock alkaloids from Socrates to poison aloes.

PubMed

Reynolds, Tom

2005-06-01

Hemlock (Conium maculatum L. Umbelliferae) has long been known as a poisonous plant. Toxicity is due to a group of piperidine alkaloids of which the representative members are coniine and gamma-coniceine. The latter is the more toxic and is the first formed biosynthetically. Its levels in relation to coniine vary widely according to environmental conditions and to provenance of the plants. Surprisingly, these piperidine alkaloids have turned up in quite unrelated species in the monocotyledons as well as the dicotyledons. Aloes, for instance, important medicinal plants, are not regarded as poisonous although some species are very bitter. Nevertheless a small number of mostly local species contain the alkaloids, especially gamma-coniceine and there have been records of human poisoning. The compounds are recognized by their characteristic mousy smell. Both acute and chronic symptoms have been described. The compounds are neurotoxins and death results from respiratory failure, recalling the effects of curare. Chronic non-lethal ingestion by pregnant livestock leads to foetal malformation. Both acute and chronic toxicity are seen with stock in damp meadows and have been recorded as problems especially in North America. The alkaloids derive biosynthetically from acetate units via the polyketide pathway in contrast to other piperidine alkaloids which derive from lysine.

Sugammadex: Appropriate Use in the Context of Budgetary Constraints.

PubMed

Cammu, Guy

2018-01-01

The purpose of this review is to assess how sugammadex impacts postoperative residual curarization using appropriate doses based on neuromuscular transmission monitoring and whether the advantages of sugammadex versus neostigmine outweigh its higher cost. An accurate assessment of neuromuscular blockade with monitoring is necessary before selecting neostigmine versus sugammadex for reversal at the end of surgery to overcome incomplete neuromuscular recovery. The main advantages of sugammadex over neostigmine are its predictability and its ability to extend the range of blockade reversal. The cost of sugammadex is greater when higher doses of sugammadex are required for antagonism of deep block. Sugammadex probably has the potential to be cost-effective compared with neostigmine if its time savings are put to productive use in clinical practice. However, to date, the economic benefits of the drug are unknown. With sugammadex, almost any degree of neuromuscular block can be antagonized within 2-3 min; neostigmine is the only reversal agent effective against benzylisoquinolines and can ideally be used for reversal of lower levels of residual paralysis. The performance of the more expensive sugammadex on improving patient outcomes may depend on several elements of clinical strategy.

Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.

PubMed

Santhanam, Navaneetha; Kumanchik, Lee; Guo, Xiufang; Sommerhage, Frank; Cai, Yunqing; Jackson, Max; Martin, Candace; Saad, George; McAleer, Christopher W; Wang, Ying; Lavado, Andrea; Long, Christopher J; Hickman, James J

2018-06-01

There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units. A system was developed in which human myotubes and motoneurons derived from stem cells were cultured in a serum-free medium in a BioMEMS construct. The system is composed of two chambers linked by microtunnels to enable axonal outgrowth to the muscle chamber that allows separate stimulation of each component and physiological NMJ function and MN stimulated tetanus. The muscle's contractions, induced by motoneuron activation or direct electrical stimulation, were monitored by image subtraction video recording for both frequency and amplitude. Bungarotoxin, BOTOX ® and curare dose response curves were generated to demonstrate pharmacological relevance of the phenotypic screening device. This quantifiable functional hNMJ system establishes a platform for generating patient-specific NMJ models by including patient-derived iPSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms.

PubMed

Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

2011-01-01

The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA(2) activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity.

The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms

PubMed Central

Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

2011-01-01

The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA2 activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity. PMID:21858249

The release of acetylcholine from post-ganglionic cell bodies in response to depolarization.

PubMed Central

Johnson, D A; Pilar, G

1980-01-01

1. Acetylcholine (Ach) release from parasympathetic ganglia cell somata was investigated in denervated avian ciliary ganglia. Three days after the input to the ganglion (the oculomotor nerve) was sectioned, all presynaptic nerve terminals had degenerated. 2. Denervated ganglia were shown to contain endogenous ACh and to be capable of synthesizing [3H]ACh from [3H]choline added to the incubation medium. 3. In response to depolarization induced by incubation in 50 mM-[K+]o, denervated ganglia released [3H]ACh into bath effluents in amounts approximately 15% of the non-denervated contralateral control. This release was shown to be Ca2+ dependent in both intact and denervated ganglia. 4. Antidromic electrical stimulation of ciliary nerves also elicited [3H]ACh release. Nicotine (1 microgram/microliter.) depolarized denervated ciliary ganglion cells and evoked release of the transmitter and this release was antagonized by curare. 5. It is concluded that the ganglionic cell bodies sysnthesized ACh and released the transmitter in response to K+ depolarization, antidromic stimulation and cholinergic agonists, despite the lack of morphological specializations usually associated with stimulus-induced release of neurotransmitter. The evidence suggests the existence of a mechanism of transmitter release which is Ca2+ dependent, probably from a cytoplasmic pool and therefore distinct from the usual vesicular release at the nerve terminal. Images Plate 1 Plate 2 PMID:6247485

Influence of temperature and reproductive state upon the jamming avoidance response in the pulse-type electric fish Brachyhypopomus pinnicaudatus.

PubMed

Lorenzo, Daniel; Macadar, Omar

2005-01-01

The electric organ discharge (EOD) in Brachyhypopomus pinnicaudatus is modified by temperature and reproductive state. We studied the influence of these variables upon a complex behavior, the jamming avoidance response (JAR). Experiments were performed in non-reproductive fish and in two groups of fish after the induction of reproductive state (by nature or by acclimation at 28 degrees C). JARs were elicited at 20 and 30 degrees C by free-run electric stimuli with different deltaLs (interval difference between stimulus and EOD). In non-reproductive fish, JARs induced by stimuli with +deltaLs showed temperature sensitivity, with smaller responses at 30 degrees C. Conversely, similar JARs were obtained at both temperatures in reproductive fish. These observations were replicated in curarized preparations. Stimuli with -deltaLs were almost ineffective in non-reproductive fish at 30 degrees C, whereas adequate JARs were shown by reproductive fish. Phase-locked stimuli were used to evaluate the duration of the low-threshold electrosensory periods preceding and following the EOD. In non-reproductive fish, the temperature step induced a shortening of these periods. The opposite effect was observed in reproductive fish, probably explaining the differences in JAR capability. A prolongation of the low-threshold periods would favor the perception of electrocommunication signals during courtship. JAR changes would be a consequence of this adaptation.

[Storing succinylcholine in prehospital settings following the recommendations of the French National Agency for the safety of medicines].

PubMed

Lefort, H; Mendibil, A; Margerin, S; Cuquel, A-C; Jost, D; Tazarourte, K; Domanski, L; Tourtier, J-P

2014-06-01

The French National Pharmaceuticals Agency (ANSM) has recommanded in July 2012 not to break the cold chain before using succinylcholine (Celocurine®). to understand the pre-clinical evolution of the conservation modes of this curare. Descriptive study before (year 2011) and after (year 2012). Online survey to French Samu/Smur. SMUR location, conservation method at clinical base, in the mobile unit (UMH) and at the patient. Principal decision criteria: evolution of the conservation modes before and after the recommendation (qualitatives variables compared with a Fisher test). Out of 101 SAMU/SMUR, 62 answered. Conservation modes of succinylcholine vials were significantly different (P<0.001). Proper conservation was observed in 26 % of the cases before and 43 % after. Mobile units (UMH) equipped with a fridge increased from one out of two to 77 %. The lack of conservation modes passive or active on UMH went from 31 % to 3.4 % with isotherms bags with ice when a fridge was not available. The destruction of capsules at current temperature in a 24-hour period increased: 22 % before, 47 % after (P=0.04). After recommendations from ANSM, conservation modes and destruction of succinylcholine in a prehospital environment were significantly impacted. Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Biological characterization of the Amazon coral Micrurus spixii snake venom: Isolation of a new neurotoxic phospholipase A2.

PubMed

Terra, Angelo L C; Moreira-Dill, Leandro S; Simões-Silva, Rodrigo; Monteiro, José Roniele N; Cavalcante, Walter L G; Gallacci, Márcia; Barros, Neuza B; Nicolete, Roberto; Teles, Carolina B G; Medeiros, Patrícia S M; Zanchi, Fernando B; Zuliani, Juliana P; Calderon, Leonardo A; Stábeli, Rodrigo G; Soares, Andreimar M

2015-09-01

The Micrurus genus is the American representative of Elapidae family. Micrurus spixii is endemic of South America and northern states of Brazil. Elapidic venoms contain neurotoxins that promote curare-mimetic neuromuscular blockage. In this study, biochemical and functional characterizations of M. spixii crude venom were performed and a new neurotoxic phospholipase A2 called MsPLA2-I was isolated. M. spixii crude venom caused severe swelling in the legs of tested mice and significant release of creatine kinase (CK) showing its myotoxic activity. Leishmanicidal activity against Leishmania amazonensis (IC50 1.24 μg/mL) was also observed, along with antiplasmodial activity against Plasmodium falciparum, which are unprecedented for Micrurus venoms. MsPLA2-I with a Mr 12,809.4 Da was isolated from the crude venom of M. spixii. The N-terminal sequencing of a fragment of 60 amino acids showed 80% similarity with another PLA2 from Micrurus altirostris. This toxin and the crude venom showed phospholipase activity. In a mouse phrenic nerve-diaphragm preparation, M. spixii venom and MsPLA2-I induced the blockage of both direct and indirect twitches. While the venom presented a pronounced myotoxic activity, MsPLA2-I expressed a summation of neurotoxic activity. The results of this study make M. spixii crude venom promising compounds in the exploration of molecules with microbicidal potential. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a retrospectıve study.

PubMed

Ozmete, Ozlem; Bali, Cagla; Cok, Oya Yalcin; Turk, Hatice Evren Eker; Ozyilkan, Nesrın Bozdogan; Civi, Soner; Aribogan, Anıs

2016-12-01

To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients. Retrospective observational study. University teaching hospital. Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study. Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation. The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered. The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded. Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium. Copyright © 2016 Elsevier Inc. All rights reserved.

Iridoids as chemical markers of false ipecac (Ronabea emetica), a previously confused medicinal plant.

PubMed

Berger, Andreas; Fasshuber, Hannes; Schinnerl, Johann; Robien, Wolfgang; Brecker, Lothar; Valant-Vetschera, Karin

2011-12-08

Several roots or rhizomes of rubiaceous species are reportedly used as the emetic and antiamoebic drug ipecac. True ipecac (Carapichea ipecacuanha) is chemically well characterized, in contrast to striated or false ipecac derived from the rhizomes of Ronabea emetica (syn. Psychotria emetica). Besides its previous use as substitute of ipecac, the latter species is applied in traditional medicine of Panama and fruits of its relative Ronabea latifolia are reported as curare additives from Colombia. Compounds of Ronabea emetica were isolated using standard chromatographic techniques, and structurally characterized by NMR spectroscopy and mass spectrometry. Organ specific distribution in Ronabea emetica as well as in Ronabea latifolia was further assessed by comparative HPLC analysis. Four iridoid-glucosides, asperuloside (1), 6α-hydroxygeniposide (2), deacetylasperulosidic acid (3) and asperulosidic acid (4) were extracted from leaves of Ronabea emetica. Rhizomes, used in traditional medicine, were dominated by 3. HPLC profiles of Ronabea latifolia were largely corresponding. These results contrast to the general tendency of producing emetine-type and indole alkaloids in species of Psychotria and closely related genera and merit chemotaxonomic significance, characterizing the newly delimited genus Ronabea. The aim of the work was to resolve the historic problem of adulteration of ipecac by establishing the chemical profile of Ronabea emetica, the false ipecac, as one of its less known sources. The paper demonstrates that different sources of ipecac can be distinguished by their phytochemistry, thus contributing to identifying adulterations of true ipecac. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Sugammadex and Ideal Body Weight in Bariatric Surgery

PubMed Central

Alessandri, Francesco; Wefki Abdelgawwad Shousha, Ahmed Abdelgawwad; Sabba, Antonio; Cutolo, Alessandra

2013-01-01

Background. The obese patients have differences in body composition, drug distribution, and metabolism. Sugammadex at T 2 recovery in a dose of 2 mg kg−1 of real body weight (RBW) can completely reverse the NMB block; in our study we investigated the safety and efficacy of Sugammadex dose based on their ideal body weight (IBW). Methods. 40 patients of both sexes undergoing laparoscopic bariatric surgery were enrolled divided into 2 groups according to the dose of Sugammadex: the first received a dose of 2 mg kg−1 of IBW and the second received a dose of 2 mg kg−1 of RBW. Both were anesthetized with doses calculated according to the IBW: fentanyl 2 μg kg−1, propofol 3 mg kg−1, rocuronium 0,6 mg kg−1, oxygen, air, and desflurane (6–8%). Maintenance doses of rocuronium were 1/4 of the intubation dose. Sugammadex was administrated at T 2 recovery. Results. The durations of intubation and maintenance doses of rocuronium were similar in both groups. In IBW group, the T 4/T 1 value of 0.9 was reached in 151 ± 44 seconds and in 121 ± 55 seconds in RBW group (P = 0.07). Discussion. Recovery times to T 4/T 1 of 0.9 are surprisingly similar in both groups without observing any postoperative residual curarization. Conclusion. Sugammadex doses calculated according to the IBW are certainly safe for a rapid recovery and absence of PORC. PMID:23840203

Contralateral-noise effects on cochlear responses in anesthetized mice are dominated by feedback from an unknown pathway

PubMed Central

Usubuchi, Hajime; Vetter, Douglas E.; Elgoyhen, A. Bélen; Thomas, Steven A.; Liberman, M. Charles

2012-01-01

Suppression of ipsilateral distortion product otoacoustic emissions (DPOAEs) by contralateral noise is used in humans and animals to assay the strength of sound-evoked negative feedback from the medial olivocochlear (MOC) efferent pathway. However, depending on species and anesthesia, contributions of other feedback systems to the middle or inner ear can cloud the interpretation. Here, contributions of MOC and middle-ear muscle reflexes, as well as autonomic feedback, to contra-noise suppression in anesthetized mice are dissected by selectively eliminating each pathway by surgical transection, pharmacological blockade, or targeted gene deletion. When ipsilateral DPOAEs were evoked by low-level primaries, contra-noise suppression was typically ∼1 dB with contra-noise levels around 95 dB SPL, and it always disappeared upon contralateral cochlear destruction. Lack of middle-ear muscle contribution was suggested by persistence of contra-noise suppression after paralysis with curare, tensor tympani cauterization, or section of the facial nerve. Contribution of cochlear sympathetics was ruled out by studying mutant mice lacking adrenergic signaling (dopamine β-hydroxylase knockouts). Surprisingly, contra-noise effects on low-level DPOAEs were also not diminished by eliminating the MOC system pharmacologically (strychnine), surgically, or by deletion of relevant cholinergic receptors (α9/α10). In contrast, when ipsilateral DPOAEs were evoked by high-level primaries, the contra-noise suppression, although comparable in magnitude, was largely eliminated by MOC blockade or section. Possible alternate pathways are discussed for the source of contra-noise-evoked effects at low ipsilateral levels. PMID:22514298

Recovery of laryngeal nerve function with sugammadex after rocuronium-induced profound neuromuscular block.

PubMed

Pavoni, Vittorio; Gianesello, Lara; Martinelli, Cristiana; Horton, Andrew; Nella, Alessandra; Gori, Gabriele; Simonelli, Martina; De Scisciolo, Giuseppe

2016-09-01

The aim of this study was to evaluate the efficacy of sugammadex in reversing profound rocuronium-induced neuromuscular block at the laryngeal adductor muscles using motor-evoked potentials (mMEPs). A prospective observational study. University surgical center. Twenty patients with American Society of Anesthesiologists physical class I-II status who underwent propofol-remifentanil anesthesia for the surgery of the thyroid gland. Patients were enrolled for reversal of profound neuromuscular block (sugammadex 16 mg/kg, 3 minutes after rocuronium 1.2 mg/kg). To prevent laryngeal nerve injury during the surgical procedures, all patients underwent neurophysiologic monitoring using mMEPs from vocal muscles. At the same time, the registration of TOF-Watch acceleromyograph at the adductor pollicis muscle response to ulnar nerve stimulation was performed; recovery was defined as a train-of-four (TOF) ratio ≥0.9. After injection of 16 mg/kg of sugammadex, the mean time to recovery of the basal mMEPs response at the laryngeal adductor muscles was 70 ± 18.2 seconds. The mean time to recovery of the TOF ratio to 0.9 was 118 ± 80 seconds. In the postoperative period, 12 patients received follow-up evaluation of the vocal cords and no lesions caused by the surface laryngeal electrode during electrophysiological monitoring were noted. Recovery from profound rocuronium-induced block on the larynx is fast and complete with sugammadex. In urgent scenarios, "early" extubation can be performed, even with a TOF ratio ≤0.9. However, all procedures to prevent postoperative residual curarization should still be immediately undertaken. Copyright © 2016 Elsevier Inc. All rights reserved.

Traditional medicine Cassia absus L. (chaksu)-pharmacological evaluation.

PubMed

Aftab, K; Atta-Ur-Rahman; Ahmed, S I; Usmanghani, K

1996-01-01

A crude extract of Cassia absus L. produced a dose dependent decrease in systemic arterial blood pressure and heart rate in pentothal anaesthetized rats. Repeated injections of the same dose of the crude extract (CA) showed tachyphylaxis. The cardio-vascular actions were not modified by pretreatment with atropine, chloropheniramine, ranitidine or propranolol in vivo. The pressor response of norepinephnine was not altered, whereas the pressor response of carotid occlusion was less when this was performed before administration of CA. Moreover, nicotine induced an increase in arterial blood pressure which was completely abolished by the CA, suggesting that the decrease in blood pressure is unlikely to be mediated via cholinergic, histaminergic or β-2-adrenergic receptor stimulation, or by α-1-adrenergic receptor blockade. Perhaps the crude extract has centrally acting/ganglion blocking action or anti-nicotinic action. In spontaneously beating guinea-pig atria, CA induced a concentration dependent decrease in force and rate of atrial contraction. Pretreatment of cardiac tissue with the crude extract blocked the pressor response of nicotine, without altering/modifying the response to isoprenaline. In the rabbit aorta, CA caused concentration-dependent relaxation of phenylephrine and K(+)-induced contractions. In the guinea-pig ileum, CA at a low concentrations significantly reduced the spasmogenic response of nicotine without modifying the effect of acetylcholine. At high concentrations, it non-specifically abolished all the spasmogenic responses to ACh, 5 HT and histamine. The neuromuscular activity of CA was found to be similar to that of d-tubocurarine in skeletal muscle preparations (Frog rectus abdominis). These results revealed that the CA of Cassia absus exerts centrally acting/ganglion blocking, anti-nicotinic, non-specific muscle relaxant and curare like activities. Copyright © 1996 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Snake bite: coral snakes.

PubMed

Peterson, Michael E

2006-11-01

North American coral snakes are distinctively colored beginning with a black snout and an alternating pattern of black, yellow, and red. They have fixed front fangs and a poorly developed system for venom delivery, requiring a chewing action to inject the venom. The severity of a coral snake bite is related to the volume of venom injected and the size of the victim. The length of the snake correlates positively with the snakes venom yield. Coral snake venom is primarily neurotoxic with little local tissue reaction or pain at the bite site. The net effect of the neurotoxins is a curare like syndrome. In canine victims there have been reports of marked hemolysis with severe anemia and hemoglobinuria. The onset of clinical signs may be delayed for as much as 10 to 18 hours. The victim begins to have alterations in mental status and develops generalized weakness and muscle fasciculations. Progression to paralysis of the limbs and respiratory muscles then follows. The best flied response to coral snake envenomation is rapid transport to a veterinary medical facility capable of 24 hour critical care and assisted ventilation. First aid treatment advocated in Australia for Elapid bites is the immediate use of a compression bandage. The victim should be hospitalized for a minimum of 48 hours for continuous monitoring. The only definitive treatment for coral snake envenomation is the administration of antivenin (M. fulvius). Once clinical signs of coral snake envenomation become manifest they progress with alarming rapidity and are difficult to reverse. If antivenin is not available or if its administration is delayed, supportive care includes respiratory support. Assisted mechanical ventilation can be used but may have to be employed for up to 48 to 72 hours.

Sugammadex antagonism of rocuronium-induced neuromuscular blockade in patients with liver cirrhosis undergoing liver resection: a randomized controlled study.

PubMed

Abdulatif, Mohamed; Lotfy, Maha; Mousa, Mahmoud; Afifi, Mohamed H; Yassen, Khaled

2018-02-05

This randomized controlled study compared the recovery times of sugammadex and neostigmine as antagonists of moderate rocuroniuminduced neuromuscular block in patients with liver cirrhosis and controls undergoing liver resection. The study enrolled 27 adult patients with Child class "A" liver cirrhosis and 28 patients with normal liver functions. Normal patients and patients with liver cirrhosis were randomized according to the type of antagonist (sugammadex 2mg/kg or neostigmine 50μg/kg). The primary outcome was the time from antagonist administration to a trainoffour (TOF) ratio of 0.9 using mechanosensor neuromuscular transmission module. The durations of the intubating and topup doses of rocuronium, the length of stay in the postanesthesia care unit (PACU), and the incidence of postoperative re curarization were recorded. The durations of the intubating and topup doses of rocuronium were prolonged in patients with liver cirrhosis than controls. The times to a TOF ratio of 0.9 were 3.1 (1.0) and 2.6 (1.0) min after sugammadex administration in patients with liver cirrhosis and controls, respectively, p=1.00. The corresponding times after neostigmine administration were longer than sugammadex 14.5 (3.6) and 15.7 (3.6) min, respectively, p<0.001. The duration of PACU stay was shorter with the use of sugammadex compared to neostigmine. We did not encounter postoperative recurarization after sugammadex or neostigmine. Sugammadex rapidly antagonize moderate residual rocuronium induced neuromuscular block in patients with Child class "A" liver cirrhosis undergoing liver resection. Sugammadex antagonism is associated with 80% reduction in the time to adequate neuromuscular recovery compared to neostigmine.

PEEP-ZEEP technique: cardiorespiratory repercussions in mechanically ventilated patients submitted to a coronary artery bypass graft surgery

PubMed Central

2011-01-01

Background The PEEP-ZEEP technique is previously described as a lung inflation through a positive pressure enhancement at the end of expiration (PEEP), followed by rapid lung deflation with an abrupt reduction in the PEEP to 0 cmH2O (ZEEP), associated to a manual bilateral thoracic compression. Aim To analyze PEEP-ZEEP technique's repercussions on the cardio-respiratory system in immediate postoperative artery graft bypass patients. Methods 15 patients submitted to a coronary artery bypass graft surgery (CABG) were enrolled prospectively, before, 10 minutes and 30 minutes after the technique. Patients were curarized, intubated, and mechanically ventilated. To perform PEEP-ZEEP technique, saline solution was instilled into their orotracheal tube than the patient was reconnected to the ventilator. Afterwards, the PEEP was increased to 15 cmH2O throughout 5 ventilatory cycles and than the PEEP was rapidly reduced to 0 cmH2O along with manual bilateral thoracic compression. At the end of the procedure, tracheal suction was accomplished. Results The inspiratory peak and plateau pressures increased during the procedure (p < 0.001) compared with other pressures during the assessment periods; however, they were within lung safe limits. The expiratory flow before the procedure were 33 ± 7.87 L/min, increasing significantly during the procedure to 60 ± 6.54 L/min (p < 0.001), diminishing to 35 ± 8.17 L/min at 10 minutes and to 36 ± 8.48 L/min at 30 minutes. Hemodynamic and oxygenation variables were not altered. Conclusion The PEEP-ZEEP technique seems to be safe, without alterations on hemodynamic variables, produces elevated expiratory flow and seems to be an alternative technique for the removal of bronchial secretions in patients submitted to a CABG. PMID:21914178

Comparative analysis of respiratory systems compliance in three different positioning (lateral, dorsal and sitting) in patients in prolonged invasive mechanical ventilation.

PubMed

Porto, Elias Ferreira; Castro, Antonio Adolfo Matos de; Leite, José Renato de Oliveira; Miranda, Saul Vitoriano; Lancauth, Auristela; Kumpel, Claudia

2008-09-01

This study is justified by the fact that in clinical practice, changes occur in patient's positioning in the bed during hospitalization in intensive care unity, it's necessary better understanding about possible adverse effects that such changes might cause mainly on the respiratory system condition. The objective this study was to evaluate if the patients positioning in bed can to alter the pulmonary complacency. All included patients were submitted to mechanical ventilation and were sedated and curarized respiratory system compliance was assessed in three different positioning: lateral, dorsal and sitting. After an alveolar recruitment maneuver, patients were placed to a position throughout two hours, and in the last five minutes the data was collected from the mechanical ventilator display. twenty eight patients were prospectively assessed. Values of respiratory system compliance in the lateral position were 37,07 ± 12,9 in the dorsal were 39,2 ± 10,5 and in the sitting 43,4 ± 9,6 mL/cmH2O. There were a statistical difference when we compared to the sitting and dorsal with lateral positioning for respiratory system compliance (p = 0.0052) and tidal volume (p < 0.001). There was a negative correlation between mean values of positive end expiratory pressure a respiratory system compliance (r = 0.59, p = 0.002). The FIO2 administered was 0.6 for the lateral positioning and 0.5 for the dorsal and sitting positioning (p = 0.049). That body positioning in patients restrained to a bed and submitted to invasive mechanical ventilation leads to pulmonary compliance, tidal volume and SpO2 oscillations. In the sitting position the pulmonary compliance is higher than in others positions.

Pharmacologically active plant metabolites as survival strategy products.

PubMed

Attardo, C; Sartori, F

2003-01-01

The fact that plant organisms produce chemical substances that are able to positively or negatively interfere with the processes which regulate human life has been common knowledge since ancient times. One of the numerous possible examples in the infusion of Conium maculatum, better known as Hemlock, a plant belonging to the family umbelliferae, used by the ancient Egyptians to cure skin diseases. The current official pharmacopoeia includes various chemical substances produced by secondary plant metabolisms. For example, the immunosuppressive drugs used to prevent organ transplant rejection and the majority of antibiotics are metabolites produced by fungal organisms, pilocarpin, digitalis, strophantus, salicylic acid and curare are examples of plant organism metabolites. For this reason, there has been an increase in research into plants, based on information on their medicinal use in the areas where they grow. The study of plants in relation to local culture and traditions is known as "ethnobotany". Careful study of the behaviour of sick animals has also led to the discovery of medicinal plants. The study of this subject is known as "zoopharmacognosy". The aim of this article is to discuss the fact that "ad hoc" production of such chemical substances, defined as "secondary metabolites", is one of the modes in which plant organisms respond to unfavourable environmental stimuli, such as an attack by predatory phytophagous animals or an excessive number of plant individuals, even of the same species, in a terrain. In the latter case, the plant organisms produce toxic substances, called "allelopathic" which limit the growth of other individuals. "Secondary metabolites" are produced by metabolic systems that are shunts of the primary systems which, when required, may be activated from the beginning, or increased to the detriment of others. The study of the manner in which such substances are produced is the subject of a new branch of learning called "ecological biochemistry".

Cholinergic interneurons in the feeding system of the pond snail Lymnaea stagnalis. II. N1 interneurons make cholinergic synapses with feeding motoneurons.

PubMed

Elliott, C J; Kemenes, G

1992-05-29

The N1 neurons are a population of interneurons active during the protraction phase of the feeding rhythm. All the N1 neurons are coupled by electrical synapses which persist in a high Mg/low Ca saline which blocks chemical synapses. Individual N1 spikes produce discrete electrotonic postsynaptic potentials (PSPS) in other N1 cells, but the coupling is not strong enough to ensure 1:1 firing. Bursts of N1 spikes generate compound PSPS in the feeding motoneurons. The sign (excitation or inhibition) of the N1 input corresponds with the synaptic barrage recorded during the protraction phase. Discrete PSPS are only resolved in a Hi-Di saline. Their variation in latency and number can be explained by variation in electrotonic propagation within the electrically coupled network of N1 cells. The excitatory postsynaptic potentials (ESPS) in the 1 cell are reduced by 0.5 mM antagonists hexamethonium (HMT), atropine (ATR), curare (d-TC) and by methylxylocholine (MeXCh), all of which block the excitatory cholinergic receptor (Elliott et al. (Phil. Trans. R. Soc. Lond. 336, 157-166 (Preceding paper.) (1992)). The 1 cell EPSPS were transiently blocked by phenyltrimethylammonium (PTMA), which is both an agonist and antagonist at the 1 cell excitatory acetylcholine (ACh) receptor (Elliott et al. 1992). The inhibitory postsynaptic potential (IPSP) in the 3 cell is blocked by bath applications of MeXCh and PTMA, which both abolish the response of the 3 cell to ACh (Elliott et. al. 1992). The effects of the cholinergic antagonists on the response of 4 cluster and 5 cells to N1 stimulation matches their response to ACh (Elliott et al. 1992). It is concluded that the population of N1 cells are multiaction, premotor cholinergic interneurons.

[Recent results on the pharmacodynamics of Strychnos malgaches alkaloids].

PubMed

Rasoanaivo, P; Ratsimamanga-Urverg, S; Frappier, F

1996-01-01

Investigation of Strychnos (Loganiaceae) shrubs and trees was initiated by their traditional uses of their inherent poisons on arrows: this led to the discovery of strychnine and curare alkaloids. Subsequently, phytochemical investigation of several Strychnos species has shown great structural diversity of the alkaloid constituent which also display various biological effects, i.e. convulsive and relaxant effects on muscles, and antimicrobial, antitumor and antihypertensive properties. Ethnobotanical field work conducted in different regions of Madagascar revealed that infusion of three Strychnos species, S. mostueoides, S. myrtoides and S. diplotricha, is used in association with subcurative doses of chloroquine to treat chronic malaria. Bioassayfractionation led to the isolation of two major bioactive components, strychnobrasiline and malagashanine. Whereas strychnobrasiline is a previously known chemical compound, malagashanine is the first in a series of a new subtype of Strychnos alkaloids. These two alkaloids are devoid of intrinsic antimalarial effects, both in vitro (IC50 = 73.0 micrograms/ml for strychnobrasiline and 69.1 micrograms/ml for malagashanine) and in vivo (10 mg/kg conferred a 5% suppression of parasitemia). When these alkaloids are combined with chloroquine at doses much lower than required for antiplasmodial effects, they greatly enhance the chloroquine action in a dose dependent manner as seen by the isobologram method. Several minor alkaloids structurally related to malagashanine were also isolated from Madagascan Strychnos. They all enhance, to greater or lesser degrees, the chloroquine effectiveness. Interestingly, there is a positive correlation between the ethnomedical use of the three Strychnos species as chloroquine adjuvants and the chloroquine-potentiating effects of malagashanine and strychnobrasiline isolated from them. After preliminary toxicological studies, infusion of stem barks of S. myrtoides in association with chloroquine was successfully evaluated in a clinical setting. Additional chemical, pharmacological and toxicological work is being conducted on these alkaloids with the aim of developing purified and standardized extracts for clinical trials. These trials will be carried out in the chloroquine-resistant regions of Madagascar which are in need of inexpensive and efficient drugs for the treatment of chloroquine-resistant malaria.

The "beneficial" effects of locomotor training after various types of spinal lesions in cats and rats.

PubMed

Rossignol, Serge; Martinez, Marina; Escalona, Manuel; Kundu, Aritra; Delivet-Mongrain, Hugo; Alluin, Olivier; Gossard, Jean-Pierre

2015-01-01

This chapter reviews a number of experiments on the recovery of locomotion after various types of spinal lesions and locomotor training mainly in cats. We first recall the major evidence on the recovery of hindlimb locomotion in completely spinalized cats at the T13 level and the role played by the spinal locomotor network, also known as the central pattern generator, as well as the beneficial effects of locomotor training on this recovery. Having established that hindlimb locomotion can recover, we raise the issue as to whether spinal plastic changes could also contribute to the recovery after partial spinal lesions such as unilateral hemisections. We found that after such hemisection at T10, cats could recover quadrupedal locomotion and that deficits could be improved by training. We further showed that, after a complete spinalization a few segments below the first hemisection (at T13, i.e., the level of previous studies on spinalization), cats could readily walk with the hindlimbs within hours of completely severing the remaining spinal tracts and not days as is usually the case with only a single complete spinalization. This suggests that neuroplastic changes occurred below the first hemisection so that the cat was already primed to walk after the spinalization subsequent to the hemispinalization 3 weeks before. Of interest is the fact that some characteristic kinematic features in trained or untrained hemispinalized cats could remain after complete spinalization, suggesting that spinal changes induced by training could also be durable. Other studies on reflexes and on the pattern of "fictive" locomotion recorded after curarization corroborate this view. More recent work deals with training cats in more demanding situations such as ladder treadmill (vs. flat treadmill) to evaluate how the locomotor training regimen can influence the spinal cord. Finally, we report our recent studies in rats using compressive lesions or surgical complete spinalization and find that some principles of locomotor recovery in cats also apply to rats when adequate locomotor training is provided. © 2015 Elsevier B.V. All rights reserved.

Sugammadex for reversal of neuromuscular blockade: a retrospective analysis of clinical outcomes and cost-effectiveness in a single center.

PubMed

Carron, Michele; Baratto, Fabio; Zarantonello, Francesco; Ori, Carlo

2016-01-01

The aim of the study is to evaluate the clinical and economic impact of introducing a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen for neuromuscular block (NMB) management. We conducted a retrospective analysis of clinical outcomes and cost-effectiveness in five operating rooms at University Hospital of Padova. A clinical outcome evaluation after sugammadex administration as first-choice reversal drug in selected patients (rocuronium-sugammadex) and as rescue therapy after neostigmine reversal (rocuronium-neostigmine-sugammadex) compared to control was performed. A cost-analysis of NMB management accompanying the introduction of a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen was carried out. To such purpose, two periods were compared: 2011-2012, without sugammadex available; 2013-2014, with sugammadex available. A subsequent analysis was performed to evaluate if sugammadex replacing neostigmine as first choice reversal drug is cost-effective. The introduction of a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen reduced the average cost of NMB management by 36%, from €20.8/case to €13.3/case. Patients receiving sugammadex as a first-choice reversal drug (3%) exhibited significantly better train-of-four ratios at extubation (P<0.001) and were discharged to the surgical ward (P<0.001) more rapidly than controls. The cost-saving of sugammadex as first-choice reversal drug has been estimated to be €2.9/case. Patients receiving sugammadex as rescue therapy after neostigmine reversal (3.2%) showed no difference in time to discharge to the surgical ward (P=0.44) compared to controls. No unplanned intensive care unit (ICU) admissions with rocuronium-neostigmine-sugammadex strategy were observed. The potential economic benefit in avoiding postoperative residual curarization (PORC)-related ICU admission in the 2013-2014 period was estimated at an average value of €13,548 (€9,316-€23,845). Sugammadex eliminated PORC and associated morbidities. In our center, sugammadex reduced the costs of NMB management and promoted rapid turnover of patients in operating rooms, with total cost-effectiveness that counteracts the disadvantages of its high cost.

Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5-hydroxytryptamine

PubMed Central

Gerschenfeld, H. M.; Tritsch, Danièle Paupardin

1974-01-01

1. Molluscan neurones have been found to show six different types of response (three excitatory and three inhibitory) to the iontophoretic application of 5-hydroxytryptamine (5-HT). The pharmacological properties of the receptors and the ionic mechanisms associated with these responses have been analysed. 2. Four of the responses to 5-HT (named A, A′, B and C) are consequent upon an increase in membrane conductance whereas the other two (named α and β) are caused by a decrease in membrane conductance. 3. The A-response to 5-HT consists of a `fast' depolarization due to an increase mainly in Na+-conductance; the A′-response is a `slow' depolarization also associated with a Na+-conductance increase. Receptors mediating the A- and A′-depolarizations have different pharmacological properties and may exist side by side on the same neurone. 4. Both the B- and C-responses are inhibitory. The B-response is a `slow' hyperpolarization due to an increase in K+-conductance, the C-response is a fast hyperpolarization associated with an increase in Cl--conductance. 5. The α-response to 5-HT is a depolarization which becomes reduced in amplitude with cell hyperpolarization and reverses at -75 mV; it is caused by a decrease in K+-conductance. The β-response is an hyperpolarization which increases in amplitude with cell hyperpolarization and reverses at -20/-30 mV. It results from a decrease in conductance to both Na+ and K+ ions. 6. The receptors involved in the 5-HT responses associated with a conductance increase may be recognized by the action of specific antagonists: 7-methyltryptamine blocks only the A-receptors, 5-methoxygramine only the B-receptors and neostigmine only the C-receptors. Curare blocks the A- and C-receptors and bufotenine, the A-, A′- and B-receptors. No specific antagonists have yet been found for the 5-HT responses caused by a conductance decrease. 7. The significance of the multiplicity of receptors is discussed. Their functional significance at synapses is analysed in the following paper. PMID:4155767

Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials.

PubMed

Carron, Michele; Zarantonello, Francesco; Tellaroli, Paola; Ori, Carlo

2016-12-01

Sugammadex has been introduced for reversal of rocuronium (or vecuronium)-induced neuromuscular blockade (NMB). Although its efficacy has been established, data are conflicting whether it is safer than neostigmine traditionally used for reversing NMB. Meta-analysis of data about effectiveness and safety of sugammadex compared to neostigmine for reversing NMB in adults was performed using the PRISMA methodology. University medical hospital. A comprehensive search was conducted using PubMed, Web of Science, and Cochrane Library electronic databases to identify English-language randomized controlled trials. Two reviewers independently selected the trials; extracted data on reversal times, incomplete reversals of NMB, and adverse events (AEs); and assessed the trials' methodological quality and evidence level. Only AEs that were related to study drug by a blinded safety assessor were considered for meta-analysis. A total of 1384 patients from 13 articles were included in this meta-analysis. Compared to neostigmine, sugammadex was faster in reversing NMB (P<.0001) and more likely to be associated with higher train-of-four ratio values at extubation (mean difference, 0.18; 95% confidence interval [CI], 0.14-0.22; P<.0001) and lower risk of postoperative residual curarization after extubation (odds ratio [OR], 0.05; 95% CI, 0.01-0.43; P=.0068). Compared to neostigmine, sugammadex was associated with a significantly lower likelihood of global AEs (OR, 0.47; 95% CI, 0.34-0.66; P<.0001), respiratory AEs (OR, 0.36; 95% CI, 0.14-0.95; P=.0386), cardiovascular AEs (OR, 0.23; 95% CI, 0.08-0.61; P=.0036), and postoperative weakness (OR, 0.45; 95% CI, 0.21-0.97; P=.0409). Sugammadex and neostigmine were associated with a similar likelihood of postoperative nausea and vomiting (OR, 1.23; 95% CI, 0.70-2.15; P=.4719), pain (OR, 1.06; 95% CI, 0.15-7.36; P=.9559), neurologic AEs (OR, 1.47; 95% CI, 0.52-4.17; P=.4699), general AEs (OR, 0.75; 95% CI, 0.47-1.21; P=.2448), and changes in laboratory tests' values (OR, 0.57; 95% CI, 0.18-1.78; P=.3368). Results from this meta-analysis suggest that sugammadex is superior to neostigmine, as it reverses NMB faster and more reliably, with a lower risk of AEs. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain–computer interfaces: communication and restoration of movement in paralysis

PubMed Central

Birbaumer, Niels; Cohen, Leonardo G

2007-01-01

The review describes the status of brain–computer or brain–machine interface research. We focus on non-invasive brain–computer interfaces (BCIs) and their clinical utility for direct brain communication in paralysis and motor restoration in stroke. A large gap between the promises of invasive animal and human BCI preparations and the clinical reality characterizes the literature: while intact monkeys learn to execute more or less complex upper limb movements with spike patterns from motor brain regions alone without concomitant peripheral motor activity usually after extensive training, clinical applications in human diseases such as amyotrophic lateral sclerosis and paralysis from stroke or spinal cord lesions show only limited success, with the exception of verbal communication in paralysed and locked-in patients. BCIs based on electroencephalographic potentials or oscillations are ready to undergo large clinical studies and commercial production as an adjunct or a major assisted communication device for paralysed and locked-in patients. However, attempts to train completely locked-in patients with BCI communication after entering the complete locked-in state with no remaining eye movement failed. We propose that a lack of contingencies between goal directed thoughts and intentions may be at the heart of this problem. Experiments with chronically curarized rats support our hypothesis; operant conditioning and voluntary control of autonomic physiological functions turned out to be impossible in this preparation. In addition to assisted communication, BCIs consisting of operant learning of EEG slow cortical potentials and sensorimotor rhythm were demonstrated to be successful in drug resistant focal epilepsy and attention deficit disorder. First studies of non-invasive BCIs using sensorimotor rhythm of the EEG and MEG in restoration of paralysed hand movements in chronic stroke and single cases of high spinal cord lesions show some promise, but need extensive evaluation in well-controlled experiments. Invasive BMIs based on neuronal spike patterns, local field potentials or electrocorticogram may constitute the strategy of choice in severe cases of stroke and spinal cord paralysis. Future directions of BCI research should include the regulation of brain metabolism and blood flow and electrical and magnetic stimulation of the human brain (invasive and non-invasive). A series of studies using BOLD response regulation with functional magnetic resonance imaging (fMRI) and near infrared spectroscopy demonstrated a tight correlation between voluntary changes in brain metabolism and behaviour. PMID:17234696

Synaptic hyperpolarization and inhibition of turtle cochlear hair cells.

PubMed

Art, J J; Fettiplace, R; Fuchs, P A

1984-11-01

Intracellular recordings were made from turtle cochlear hair cells in order to examine the properties of the post-synaptic potentials evoked by electrical stimulation of the efferent axons. Single shocks to the efferents generated a hair cell membrane hyperpolarization with an average amplitude generally less than 1 mV and lasting for about 100 ms. With short trains of shocks, the size of the post-synaptic potential grew markedly to a maximum of 20-30 mV. The interaction between pairs of shocks separated by a varying interval was studied. For an interval of 4 ms, the response to the second shock was increased on average by a factor of 3 and the conditioning effect of the first shock decayed with a time constant of about 100 ms. We suggest the augmentation in response to trains of shocks may be partly due to facilitation of efferent transmitter release. The efferent post-synaptic potentials could be reversibly abolished by perfusion with perilymphs containing 3 microM-curare or atropine, and infusion of acetylcholine gave a transient membrane hyperpolarization. These observations are consistent with efferent action being mediated via a cholinergic synapse onto the hair cells. The post-synaptic potentials could be reversed in polarity by injection of hyperpolarizing currents through the recording electrode. The reversal potential was estimated as about -80 mV, 30 mV negative to the resting potential. Near reversal, a small brief depolarization was evident and may constitute a minor component of the synaptic response. The value of the reversal potential was unaffected by substitution of the perilymphatic chloride, but was altered in a predictable manner by changes in extracellular potassium concentration indicating that the post-synaptic potentials arise mainly by an increase in the permeability of the hair cell membrane to potassium ions. Throughout the post-synaptic hyperpolarization there was a reduction in the sensitivity of the hair cell to tones at its characteristic frequency. The desensitization, maximal for low sound pressures, varied in different cells from a factor of 1.6 to 28. At the peak of the largest synaptic potentials, the receptor potential remained negative to the resting potential with all but the loudest characteristic frequency tone s. We suggest that there are two factors in efferent inhibition; one a r duction in the receptor potential at the hair cell's characteristic frequency and the other a hyperpolarization of its membrane potential which should reduce the release of excitatory transmitter onto the afferent terminals.

Use of neuromuscular blockers and neostigmine for general anesthesia and its association with neuraxial blockade

PubMed Central

Santos, Filipe Nadir Caparica; Braga, Angélica de Fátima de Assunção; Junqueira, Fernando Eduardo Feres; Bezerra, Rafaela Menezes; de Almeida, Felipe Ferreira; Braga, Franklin Sarmento da Silva; Carvalho, Vanessa Henriques

2017-01-01

Abstract This research aimed to assess the use of neuromuscular blockers (NMB) and its reversal, associated or not with neuraxial blockade, after general anesthesia. This retrospective study analyzed 1295 patients that underwent surgery with general anesthesia at Prof. Dr. José Aristodemo Pinotti Hospital in 2013. The study included patients aged >1 year, with complete, readable medical charts and anesthetic records. Rocuronium (ROC) was the most used NMB (96.7%), with an initial dose of 0.60 (0.52–0.74) mg/kg and total dose of 0.38 (0.27–0.53) mg/kg/h. In 24.3% of the cases, neuraxial blockade was associated with a significantly longer anesthesia (P < .001) than in cases without neuraxial block, regardless of technique (total intravenous (TIV) vs intravenous and inhalational (IV+IN)). In 71.9% of the cases, a single dose of NMB was used. Patients under TIV general anesthesia associated with neuraxial blockade had a lower total dose of ROC (mg/kg/h) in comparison with TIV GA alone (0.30 (0.23–0.39) and 0.42 (0.30–0.56) mg/kg/h, respectively, P < .001). The same was observed for patients under IV+IN GA (0.32 (0.23–0.41) and 0.43 (0.31–0.56) mg/kg/h, respectively, P < .001). The duration of anesthesia was longer according to increasing number of additional NMB doses (P < .001). Dose of neostigmine was 2.00 (2.00–2.00) mg or 29.41 (25.31–33.89) μg/kg. The interval between neostigmine and extubation was >30 minutes in 10.9% of cases. The most widely used NMB was ROC. Neuroaxial blockade (spinal or epidural) was significantly associated with reduced total dose of ROC (mg/kg/h) during general anesthesia, even in the absence of neuromuscular monitoring and regardless of general anesthetic technique chosen. In most cases, neostigmine was used to reverse neuromuscular block. The prolonged interval between neostigmine and extubation (>30 minutes) was neither associated with total doses of ROC or neostigmine, nor with the time of NMB administration. This study corroborates the important role of quantitative neuromuscular monitors and demonstrates that neuraxial blockade is associated with reduced total ROC dose. Further studies are needed to evaluate the possible role of neuraxial blockade in reducing the incidence of postoperative residual curarization. PMID:28658142

Structure-function relationship in the binding of snake neurotoxins to the torpedo membrane receptor.

PubMed

Chicheportiche, R; Vincent, J P; Kopeyan, C; Schweitz, H; Lazdunski, M

1975-05-20

The Cys30-Cus34 bridge present in all long neutotoxins (71-74 amino acids, 5 disulfide bridges), but not in short toxins (60-63 amino acids, 4 disulfide bridges), is exposed at the surface since it can be reduced rapidly and selectively by sodium borohydride. Reduction and alkylation of the Cys30-Cys34 bridge of Naja haje neurotoxin III hardly alter the conformational properties of this model long toxin. Although alkylation by iodoacetic acid of th -SH groups liberated by reduction abolishes the toxicity, alkylation by iodoacetamide or ethylenimine does not affect the curarizing efficacy of the toxin. The Cys30-Cys34 bridge is not very important for the toxic activity of long neurotoxins. Reduction of the Cys30-Cys34 bridge followed by alkylation with radioactive iodoacetamide gave a labeled and active toxin which is a convenient derivative for binding experiments to the toxin receptor in membranes of the Torpedo electric organ. The binding capacity of these membrane is 1200 pmol of toxin/mg of membrane protein. The dissociation constant of the modified toxin-receptor complex at pH 7.4, 20 degrees is 10 minus 8m. Reduction with carbroxamidomethylation of the Cys30-Cys34 bridge decreases the affinity of the native Naja haje toxin only by a factor of 15. Carboxymethylation after reduction prevents binding to the membrane receptor. The binding properties of the derivative obtained by reduction and aminoethylation of Cys30-Cys34 are very similar to those of native neurotoxin III; the affinity is decreased only by a factor of 5. Binding properties to Toredo membrane of long neurotoxins (Naja haje neurotoxin III) and short neurotoxins (Naje haje toxin I and Naja mossambica toxin I) have been compared. Dissociation constants of receptor-long neurotoxin and receptor-short neurotoxin complexes are very similar (5.7 minus 8.2 times 10(-10) M at pH 7.4, 20degrees. However, the kinetics of complex formation and complex dissociation are quite different. Short neurotoxins associate 6-7 times faster with the toxin receptor and dissociate about 5-9 times faster that long neurotoxins. Acetylation and dansylation of Lys53 and Lys 27 decrease the affinity of long and short toxins for their receptor by a factor of about 200 at pH 7.4, 20 degrees, mainly because of the slower rate of association with the receptor.

Medicina integrativa en América: De qué forma se está practicando la medicina integrativa en los centros clínicos en los Estados Unidos

PubMed Central

Horrigan, Bonnie; Lewis, Sheldon; Abrams, Donald I.; Pechura, Constance

2012-01-01

RESUMEN EJECUTIVO El impulso para desarrollar e implementar estrategias de medicina integrativa está enraizado en el deseo de mejorar la atención al paciente. The Bravewell Collaborative, una organización sin ánimo de lucro dedicada a la mejora de la atención sanitaria, define la medicina integrativa como “un enfoque de la medicina que coloca al paciente en el centro y se dirige al conjunto completo de influencias físicas, emocionales, mentales, sociales, espirituales y ambientales que afectan a la salud de la persona. Con una estrategia personalizada que considera las condiciones, necesidades y circunstancias únicas del paciente, utiliza las intervenciones más apropiadas de una variedad de disciplinas científicas para curar la afección y la enfermedad y ayudar a las personas a recobrar y mantener una salud óptima”. En las pasadas dos décadas, se ha documentado un número creciente de centros clínicos que proporcionan medicina integrativa, el número de facultades y escuelas médicas que enseñan estrategias integrativas, el número de investigadores que estudian intervenciones integrativas, y el número de pacientes que solicitan cuidados integrativos. Pero se desconocía si la medicina integrativa se estaba ofreciendo de manera igual, similar, o dispar. Además, mientras que los estudios anteriores se centraban en la prevalencia y el uso de la medicina complementaria o alternativa (MCA) por parte de los pacientes1,2 o de los médicos en hospitales3, enumerando la utilización de terapias MCA individuales, se había recogido muy poca información con respecto a la práctica real de la medicina integrativa que, por definición, trata a la persona en su conjunto. En 2011, The Bravewell Collaborative encargó una encuesta para determinar la forma en que la medicina integrativa se estaba practicando en los Estados Unidos: (1) describiendo las poblaciones de pacientes y las afecciones sanitarias tratadas más habitualmente; (2) definiendo las prácticas y modelos fundamentales de atención; (3) determinando cómo se reembolsaban los servicios; (4) identificando los valores y los principios subyacentes a la atención; y (5) determinando los factores principales que impulsan una implementación satisfactoria.

The interaction between hexamethonium and tubocurarine on the rat neuromuscular junction.

PubMed Central

Rang, H. P.; Rylett, R. J.

1984-01-01

The ability of hexamethonium (C6) to reverse the neuromuscular blocking action of tubocurarine (Tc) has been reinvestigated at the voltage clamped endplate of the omohyoid muscle of rat. The possibility that a weak anticholinesterase action of C6 could contribute to the paradoxical potentiation of the peak amplitude of the endplate response has been examined. C6 (50-200 microM) caused an increase in the amplitude of nerve-evoked endplate currents (e.p.cs) recorded in the presence of 0.6 microM Tc. The effect decreased with hyperpolarization of the muscle fibre. Irreversible inhibition of acetylcholinesterase resulted in a loss of the anti-curare effect of C6. C6 did not cause an increase in e.p.c. amplitude when acetylcholine (ACh) receptors were blocked irreversibly by alpha-bungaratoxin. When transmission was blocked by increased Mg2+ concentration, C6 (50-400 microM) reduced the amplitude of e.p.cs without appreciably affecting their time course. C6 caused a decrease in the amplitude of miniature endplate currents (m.e.p.cs) the effect being slightly increased when the fibre was hyperpolarized. An e-fold increase in the effectiveness of C6 occurred with approximately 58 mV hyperpolarization. High concentrations (greater than 400 microM) affected the time course of m.e.p.cs in a manner suggestive of open channel block, but this was not evident at 200 microM, the concentration that was most effective in reversing Tc block. When tested against responses to short ionophoretic pulses of agonists, C6 was less effective against ACh (EC50ca. 300 microM) than against carbachol (CCh) (EC50 100 microM). When cholinesterase was irreversibly inhibited, C6 blocked responses to both agonists equally (EC50ca. 100 microM). The effectiveness of C6 in blocking the action of CCh was reduced 10 fold in the presence of 0.6 microM Tc, implying that the two antagonists compete for the same binding site. C6 (50-200 microM) in the presence of Tc (0.6 microM) increased the response to ionophoretically applied ACh but not that to CCh. C6 was equipotent in blocking m.e.p.cs and responses to ionophoretically applied ACh whereas Tc was more potent against the exogenously applied agonist. C6 was a weak inhibitor of acetylcholinesterase activity in rat muscle homogenates (EC50 1.5 mM). The results are discussed in terms of the kinetic hypothesis advanced by Ginsborg & Stephenson (1974) to account for the Tc reversal phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:6141831

Healing war wounds and perfuming exile: the use of vegetal, animal, and mineral products for perfumes, cosmetics, and skin healing among Sahrawi refugees of Western Sahara

PubMed Central

2012-01-01

Background Over the past decade, there has been growing interest within ethnobiology in the knowledge and practices of migrating people. Within this, scholars have given relatively less attention to displaced people and refugees: to the loss, maintenance, and adaptation of refugees’ ethnobiological knowledge, and to its significance for refugees’ wellbeing. This study focuses on cosmetics and remedies used to heal skin afflictions that are traditionally used by Sahrawi refugees displaced in South Western Algerian refugee camps. Methods The research methods included a structured survey carried out with 37 refugee households, semi-structured interviews with 77 refugees, 24 retrospective interviews with refugees and other knowledgeable informants, and a voucher specimen collection of the plants and products cited. Results We recorded the use of 55 plant species, nine animal species, and six mineral products used within the three main use categories discussed in this paper: 1) Remedies for health issues that are typical of the desert environment where the Sahrawi once lived as nomads and now live as refugees (e.g. eye afflictions); 2) Remedies for wounds that are influenced by the Sahrawi’s recent history of guerrilla warfare; and 3) Cosmetics and products used for body care, decoration and perfuming (e.g. hair care, teeth cleansing, henna use) and for aromatizing the air inside of tents and which are widely used in everyday life and social practices. Conclusions We discuss the changes that have occurred in the patterns of use and procurement of these products with exile and sedentarization in refugee camps, and conclude that refugees are not simply passive recipients of national and international aid, but rather struggle to maintain and recover their traditional ethnobiological practices in exile. Finally, we suggest further research into the ethnobiological practices and knowledge of displaced populations. Resumen Sanando las heridas de guerra y perfumando el exilio: el uso de productos vegetales, animales y minerales con fines de perfumería, cosmética y curativos de la piel entre los refugiados saharauis del Sáhara Occidental. Antecedentes Durante la última década ha habido un creciente interés en los estudios etnobiológicos de los conocimientos y prácticas de las personas que migran. Dentro de esta tendencia, los estudiosos han prestado relativamente menor atención a las personas desplazadas y a los refugiados: a la pérdida, el mantenimiento y la adaptación de sus conocimientos etnobiológicos, y su importancia para el bienestar de los refugiados. Este estudio se centra en los cosméticos y remedios para curar problemas de la piel tradicionalmente utilizados por los refugiados saharauis en los campamentos de desplazados al sudoeste de Argelia. Métodos Los métodos de investigación que se utilizaron son: una encuesta estructurada con 37 familias de refugiados, entrevistas semi-estructuradas con 77 refugiados, 24 entrevistas retrospectivas con refugiados e informantes conocedores, y una colección de muestra de las plantas y productos citados. Resultados Se registró el uso de 55 especies vegetales, nueve especies animales, y seis productos minerales utilizados en tres principales categorías de usos: 1) Recursos contra los problemas de salud característicos del entorno desértico donde una vez vivieron los saharauis como nómadas y donde ahora viven como refugiados (por ejemplo problemas en los ojos); 2) Remedios para heridas que reflejan la historia reciente de guerra de guerrilla de los nómadas saharauis; y 3) Cosméticos y productos utilizados para el cuidado del cuerpo, decoración y perfumes (por ejemplo, atención al cabello, limpieza de dientes, uso del henna) y como aromatizantes del aire al interior de las tiendas, que son ampliamente utilizados en la vida y las prácticas sociales cotidianas de los refugiados. Conclusiones En la discusión, se analizan los cambios que se han producido en los patrones de uso y en la adquisición de estos productos durante el exilio. Llegamos a la conclusión de que los refugiados no son recipientes pasivos de la ayuda nacional e internacional, sino más bien luchan para mantener y recuperar sus prácticas tradicionales etnobiológicas en el exilio. Finalmente, sugerimos nuevas direcciones para la investigación de las prácticas y los conocimientos etnobiológicos de las poblaciones desplazadas. PMID:23270531