A comparison of the antidotal effects of three oximes against an organophosphate on chick skeletal muscle

Background: One of the most toxic effects of organophosphorus poisoning (OP) is the paralysis of skeletal muscles. The oximes are a group of available antidotes. This study investigated the effects of different concentrations of paraoxon on the function of skeletal muscle and reversal or prevention of these effects by three different oximes (i.e., pralidoxime, obidoxime, and HI-6). Materials and Methods: This study was conducted based on the chicken biventer cervices (CBC) nerve-muscle preparation and the use of twitch tension recording technique. The twitches of the CBC were evoked by stimulating the motor nerve at 0.1 Hz with pulses of 0.2 msec duration and a voltage greater than that required to produce the maximum response. Moreover, twitches and contractures were recorded isotonically using Grass Biosystems. Results: Paraoxon at 0.1 µM induced a significant increase (more than 100%) in the twitch amplitude, while higher concentrations (0.3 and 1µM) induced partial or total contracture. Therefore, paraoxon at a concentration of 0.1 µ M was used to examine the capability of oximes to prevent or reverse its effects. Pralidoxime, obidoxime, and HI-6 dose-dependently prevented (when it was used as pre-treatment, 20 min before or at the same time of administration of the toxin) and reversed (when it was used as post-treatment, 20 min after the administration of the toxin) the effect of paraoxon. Conclusion: In conclusion, these results revealed that oximes were very useful in the prevention and reversal of the OP toxic effects on the skeletal muscle. Moreover, it was suggested that oximes were more effective when used as pre-treatment. Pralidoxime was more potent than obidoxime and HI-6. The HI-6, which is a newer oxime, was unexpectedly less effective than the other two.

1998 ◽  
Vol 274 (3) ◽  
pp. H860-H867 ◽  
Author(s):  
Brian H. Annex ◽  
Carol E. Torgan ◽  
Pengnian Lin ◽  
Doris A. Taylor ◽  
Michael A. Thompson ◽  
...  

Vascular endothelial growth factor (VEGF) causes endothelial cell proliferation in vitro and angiogenesis in vivo. Glycolytic skeletal muscles have a lower capillary density than oxidative muscles but can increase their capillary density and convert to a more oxidative phenotype when subject to chronic motor nerve stimulation (CMNS). We used Western analysis and immunohistochemical techniques to examine VEGF protein in a rabbit CMNS model of glycolytic skeletal muscle and in muscles with innate glycolytic versus oxidative phenotypes. VEGF protein per gram of total protein was increased in stimulated vs. control muscles 2.9 ± 1.0, 3.6 ± 1.3, 3.1 ± 0.5, 4.4 ± 1.6, and 2.7 ± 0.3 times after 3 ( n = 4), 5 ( n = 2), 10 ( n = 3), 21 ( n = 3), and 56 ( n = 2) days, respectively. VEGF protein was increased 3.1 ± 0.5 times ( P < 0.005) before (3, 5, and 10 days) and remained elevated 3.7 ± 1.0 times ( P < 0.05) after (21 and 56 days) the transition to an oxidative phenotype. By immunohistochemistry, VEGF protein was found primarily in the matrix between stimulated muscle fibers but not in the myocytes. In addition, VEGF protein was consistently lower in innate glycolytic compared with oxidative muscles. These findings suggest that VEGF plays a role in the alteration and maintenance of vascular density in mammalian skeletal muscles.


1987 ◽  
Vol 62 (6) ◽  
pp. 2507-2511 ◽  
Author(s):  
C. M. Donovan ◽  
J. A. Faulkner

The properties of mammalian skeletal muscle demonstrate a high degree of structural and functional plasticity as evidenced by their adaptability to an atypical site after cross-transplantation and to atypical innervation after cross-innervation. We tested the hypothesis that, regardless of fiber type, skeletal muscles composed of regenerating fibers adapt more readily than muscles composed of surviving fibers when placed in an atypical site with atypical innervation. Fast muscles of rats were autografted into the site of slow muscles or vice versa with the donor muscle innervated by the motor nerve to the recipient site. Surviving fibers in donor muscles were obtained by grafting with vasculature intact (vascularized muscle graft), and regenerating fibers were obtained by grafting with vasculature severed (free muscle graft). Our hypothesis was supported because 60 days after grafting, transposed muscles with surviving fibers demonstrated only a slight change from the contractile properties and fiber typing of donor muscles, whereas transplanted muscles with regenerating fibers demonstrated almost complete change to those of the muscle formerly in the atypical site.


2004 ◽  
Vol 47 (2) ◽  
pp. 111-114 ◽  
Author(s):  
Jiří Kassa

1. The influence of the time of administration of antidotal treatment consisting of anticholinergic drug (atropine) and oxime (pralidoxime, obidoxime, HI-6 or trimedoxime) on its effectiveness to eliminate tabun-induced lethal effects was studied in mice. 2. The therapeutic efficacy of antidotal treatment of tabun-induced acute poisoning depends on the time of its administration when obidoxime or the oxime HI-6 was used as an acetylcholinesterase reactivator. 3. Pralidoxime is practically ineffective to eliminate acute toxic effects of tabun regardless of the time of its administration. 4. Our results show that trimedoxime seems to be the most effective to eliminate lethal effects of tabun. In addition, its efficacy does not decrease when it is administered 5 min after tabun poisoning. 5. The findings support the hypothesis that trimedoxime appears to be the most suitable oxime to counteract acute toxicity of tabun because of its ability to eliminate lethal effects of tabun when it is injected 5 min after tabun challenge on the contrary to other oximes tested.


Author(s):  
S.A. Moiseev

The question of physiological function variability is of great theoretical interest, since it is a part of the theory of human voluntary movement control. The skeletal muscle control system should probably have a mechanism to reduce or limit the range of its possible variations. Presumably, the organization of the motor system elements according to the principle of muscular synergy is of such a nature. The objective of the work is to study variations and signs of the coordinated bioelectric activity of skeletal muscles in one of the resulting archery phases. Materials and Methods. The study enrolled 5 highly qualified sportsmen (Master of Sport, International Master of Sport). Archers shot 10 series of 3 shots, target distance 18 m, indoors. Simultaneous recording of electrical activity of 12 skeletal muscles of the upper limb girdle and a 3D video sequence was made. The authors analyzed indicators of distribution, descriptive and variation statistics for grouped data. Multiple regression analysis was used to identify signs of consistent muscle activity. Results. Variability magnitudes, characterized by statistical parameters, established for the turn-off-peak characteristics of various muscles, did not have an explicit dependence. Muscles with relatively high scattering parameters in terms of the EMG average amplitude could have a small variation in the average number of EMG turns. The radial flexor of the left hand wrist was a part of muscular synergy in 90 % of cases, the anterior part of the left limb deltoid muscle – in 80 % of cases, the lower and upper beams of the right and left cowl muscle – in 70 % of cases. Other muscles under consideration were their part in less than 60 % of cases. Conclusion. The system of skeletal muscles that are actively involved in the resulting phases of precision movement can be controlled according to the mechanism of functional synergy formation, which probably helps to reduce the range of possible variations in the parameters of muscle electroactivity. Keywords: variability, archery, electromyography, coordination structure, muscle synergy. Вопрос вариативности физиологических функций представляет интерес в теоретическом плане, поскольку является частью теории управления произвольными движениями человека. Система управления скелетными мышцами, вероятно, должна иметь механизм, позволяющий сократить или ограничить диапазон возможных ее вариаций. Таковым, предположительно, является организация элементов моторной системы по принципу мышечных синергий. Цель работы – изучение вариаций и признаков согласованной биоэлектрической активности скелетных мышц в одной из результирующих фаз выстрела из лука. Материалы и методы. В исследованиях приняли участие 5 высококвалифицированных спортсменов (МС, МСМК). Лучники выполняли 10 серий по 3 выстрела с дистанции 18 м в крытом помещении. Производилась синхронная регистрация электрической активности 12 скелетных мышц верхнего плечевого пояса и 3D-видеоряда. Анализировались показатели распределения, описательной и вариационной статистики для сгруппированных данных. Для выявления признаков согласованной активности мышц применялся множественный регрессионный анализ. Результаты. Величины вариативности, характеризуемые статистическими параметрами, установленные для турн-аплитудных характеристик различных мышц, не имели явной зависимости. Мышцы, имеющие относительно высокие параметры разброса значений по показателю средней амплитуды ЭМГ, могли иметь небольшую вариативность среднего числа турнов ЭМГ. Лучевой сгибатель кисти левой руки являлся частью мышечной синергии в 90 % случаев, передняя часть дельтовидной мышцы левой конечности – в 80 %, нижние и верхние пучки трапециевидной мышцы правой и левой сторон – в 70 %. Другие исследуемые мышцы являлись их частью в менее чем 60 % случаев. Выводы. Управление системой скелетных мышц, принимающих активное участие в реализации одной из результирующих фаз точностного движения, может осуществляться по механизму образования функциональных синергий, что, вероятно, способствует снижению диапазона возможных вариаций параметров электроактивности мышц. Ключевые слова: вариативность, стрельба из лука, электромиография, координационная структура, мышечные синергии.


2021 ◽  
Vol 12 ◽  
pp. 204173142098133
Author(s):  
Juan M. Fernández-Costa ◽  
Xiomara Fernández-Garibay ◽  
Ferran Velasco-Mallorquí ◽  
Javier Ramón-Azcón

Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudia Cristina Biguetti ◽  
Joel Ferreira Santiago Junior ◽  
Matthew William Fiedler ◽  
Mauro Toledo Marrelli ◽  
Marco Brotto

AbstractThe aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles. We designed the study according to PRISMA guidelines. Studies for qualitative and quantitative analyses were selected according to the following inclusion criteria: English language; size of sample (> 5 patients), adult (> age of 18) patients, treated with CQ/HCQ for inflammatory diseases, and presenting and not presenting with toxic effects on skeletal muscles. We collected data published from 1990 to April 2020 using PubMed, Cochrane Library, EMBASE, and SciELO. Risk of bias for observational studies was assessed regarding the ROBIN-I scale. Studies with less than five patients (case reports) were selected for an additional qualitative analysis. We used the software Comprehensive Meta-Analysis at the confidence level of 0.05. We identified 23 studies for qualitative analysis (17 case-reports), and five studies were eligible for quantitative analysis. From case reports, 21 patients presented muscle weakness and confirmatory biopsy for CQ/HCQ induced myopathy. From observational studies, 37 patients out of 1,367 patients from five studies presented muscle weakness related to the use of CQ/HCQ, and 252 patients presented elevated levels of muscle enzymes (aldolase, creatine phosphokinase, and lactate dehydrogenase). Four studies presented data on 34 patients with confirmatory biopsy for drug-induced myopathy. No study presented randomized samples. The chronic use of CQ/HCQ may be a risk for drug-induced myopathy. There is substantiated need for proper randomized trials and controlled prospective studies needed to assess the clinical and subclinical stages of CQ/HCQ -induced muscle myopathy.


1977 ◽  
Vol 55 (12) ◽  
pp. 1241-1243 ◽  
Author(s):  
N. Bégin-Heick ◽  
H. M. C. Heick

The activity of lipoprotein lipase (LPL) in the heart, diaphragm, and soleus muscles was markedly increased in cold-acclimated rats and it was even greater in rats treated with oxytetracycline (OTC) while exposed to cold. Other skeletal muscles studied had low and variable activities which were not significantly increased by cold acclimation or by cold plus OTC treatment. It appears therefore that, apart from the heart and the muscles involved in respiratory movements, LPL activity is primarily associated with those muscles which contain a predominance of slow-twitch oxidative fibers, and that the enzyme in muscle, heart, and diaphragm responds to cold acclimation and cold plus OTC treatment in a parallel fashion in these tissues.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 56-56
Author(s):  
Hiroaki Nozawa ◽  
Shigenobu Emoto ◽  
Koji Murono ◽  
Yasutaka Shuno ◽  
Soichiro Ishihara

56 Background: Systemic chemotherapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is largely unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic chemotherapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy. Methods: We reviewed 98 stage IV CRC patients who received systemic chemotherapy in our hospital. According to the treatment setting, patients were divided into the ‘Conversion’, ‘Neoadjuvant chemotherapy (NAC)’, and ‘Palliation’ groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during chemotherapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the Conversion group. Results: The mean SMI increased by 8.0% during chemotherapy in the Conversion group (n = 38), whereas it decreased by 6.2% in the NAC group (n = 18) and 3.7% in the Palliation group (n = 42, p < 0.0001). Moreover, patients with increased SMI during chemotherapy had a better overall survival (OS) than those whose SMI decreased in the Conversion group (p = 0.021). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio: 0.26). Conclusions: Stage IV CRC patients who underwent conversion to resection often had an increased SMI. As such an increase in SMI further conveys a survival benefit in conversion therapy, it may be important to make efforts to preserve muscle mass by meticulous approaches, such as nutritional support, muscle exercise programs, and pharmacological intervention even during chemotherapy in patients with metastatic CRC.


2021 ◽  
Vol 21 ◽  
Author(s):  
Vaishali K. ◽  
Nitesh Kumar ◽  
Vanishree Rao ◽  
Rakesh Krishna Kovela ◽  
Mukesh Kumar Sinha

: Skeletal muscles must generate and distribute energy properly in order to function perfectly. Mitochondria in skeletal muscle cells form vast networks to meet this need, and their functions may improve as a result of exercise. In the present review, we discussed exercise-induced mitochondrial adaptations, age-related mitochondrial decline, and a biomarker as a mitochondrial function indicator and exercise interference.


2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Tien Tuan Dao ◽  
Marie-Christine Ho Ba Tho

Finite elasticity theory has been commonly used to model skeletal muscle. A very large range of heterogeneous constitutive laws has been proposed. In this review, the most widely used continuum models of skeletal muscles were synthetized and discussed. Trends and limitations of these laws were highlighted to propose new recommendations for future researches. A systematic review process was performed using two reliable search engines as PubMed and ScienceDirect. 40 representative studies (13 passive muscle materials and 27 active muscle materials) were included into this review. Note that exclusion criteria include tendon models, analytical models, 1D geometrical models, supplement papers, and indexed conference papers. Trends of current skeletal muscle modeling relate to 3D accurate muscle representation, parameter identification in passive muscle modeling, and the integration of coupled biophysical phenomena. Parameter identification for active materials, assumed fiber distribution, data assumption, and model validation are current drawbacks. New recommendations deal with the incorporation of multimodal data derived from medical imaging, the integration of more biophysical phenomena, and model reproducibility. Accounting for data uncertainty in skeletal muscle modeling will be also a challenging issue. This review provides, for the first time, a holistic view of current continuum models of skeletal muscles to identify potential gaps of current models according to the physiology of skeletal muscle. This opens new avenues for improving skeletal muscle modeling in the framework of in silico medicine.


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