182 research outputs found

    The mode of action of muscle relaxants and allied drugs

    Get PDF
    The studies described in this thesis fall into two main parts. Part one is devoted first to an investigation of the mechanism of the antihypertensive action of 10-methoxydeserpidine and some allied compounds and second to that of chlorothiazide and some other thiazide diuretics. Part two describes investigations carried out to study the nature and mechanism of the muscle relaxant activity of a group of volatile anaesthetics including ether, chloroform, halothane and methyl-n-propyl ether. 10-Methoxydeserpidine is a structural isomer of reserpine, the methoxy group in ring A being on C(10) instead of on C(11). It has been shown clinically to possess mild antihypertensive activity qualitatively similar to that of reserpine but to be devoid of the central nervous system depressant effects characteristic of reserpine. Work was undertaken to investigate the mechanisms by which 10-methoxydeserpidine exerted its antihypertensive actions. Experimental evidence suggests that 10-methoxydeserpidine causes a generalised depression of preparations of isolated cardiac muscle, vascular and intestinal smooth muscle and skeletal muscle. It does not prolong pentobarbitone-induced sleeping time in mice and has no effect on gastrointestinal motility in the rat or the mouse. 10-Methoxy-deserpidine was found to depress the in vitro respiration of rat brain and liver slices and also to inhibit the in vitro adenosine triphosphatase activity of rat brain, liver and skeletal muscle homogenates. From the data presented, it was concluded that 10-methoxydeserpidine exerted its antihypertensive actions by virtue of an effect at peripheral sites and had little central nervous system depressant activity. It may act by interfering with tissue metabolism at cellular levels probably influencing that part which supplies the energy required for muscular contraction and the maintenance of tone. Studies were also canrried out to investigate the mode of anti-hypertensive action of the diuretic and saluretic agent chlorothiazide and some allied compounds. It was shown that chlorothiazide produced no observable fall in the blood pressure level of the normotensive anaesthetised cat or rat but a slight inhibition of the hypertensive response to adrenaline in the cat and adrenaline and noradrenaline in the rat was noted. Chlorothiazide inhibited the responses of isolated isolated strips of horse carotid artery to adrenaline, noradrenaline, 5-hydroxytryptamine and acetylcholine. It also produced a significant depression of the uptake of sodium-24 by isolated strips of rabbit thoracic aorta but did not modify the adenosine triphosphatase activity of rat skeletal muscle homogenates, tending, thereby, to indicate that the supply of energy yielded by adenosine triphosphate for the flux of sodium ions was not interfered with. The significant depression of the uptake of sodium-24 by strips of rabbit aorta suggested that chlorothiazide might reduce the sodium content of the artery wall by depressing sodium uptake from the plasma or extracellular fluids. A fall in the sodium content of the artery wall may also reduce their water content and by reducing the swelling or oedema, lead to a decrease in the peripheral resistance. This may in turn cause a fall in the arterial blood pressure level. In Part 2, a study has been made upon the muscle relaxant action of ether, halothane, chloroform and methy-n-propyl ether. It has been shown that these volatile anaesthetics cause an increase in the permeability of the muscle cell membrane to sodium and potassium ions. An increase in the uptake of sodium-24, a corresponding decrease in the uptake of potassium-42 and an increase in the efflux of potassium-42 both in isolated tissue preparations and in the intact cat were also observed. Ether and other volatile anaesthetics were found to inhibit the acetylcholine acetylcholine-induced contractions of the isolated frog rectus abdominis muscle. This inhibitor effect was preceded by a reversible contracture and an increase in the efflux of potassium ions. In the same preparation, ether caused a potentiation of the effect of tubocurarine on acetylcholine-induced contractions. Ether was found to be capable of depressing neuromuscular transmission in the rat phrenic-nerve diaphragm preparation, an effect which was also associated with an increase in the efflux of potassium ions. Ether produced an inhibition of the indirectly induced contractions of the gastrocnemius muscle of the pentobarbitone-anaesthetised cat. This was associated with an increase in the serum potassium-42 level. Adrenaline and neostigmine were found to antagonise the effects of ether on muscular contractions but produced an increase in the serum potassium-42 level. Depolarising agents have also been shown to cause an increase in the permeability of the cell membrane. From a consideration of the experimental results, it was concluded that the muscle relaxant actions of ether and other volatile anaesthetics were due to a mechanism which resembled that of depolarising agents rather than that of non-depolarizing drugs

    A new approach for cell formation and scheduling with assembly operations and product structure

    Get PDF
    In this paper, a new formulation model for cellular manufacturing system (CMS) design problem is proposed. The proposed model of this paper considers assembly operations and product structure so that it includes the scheduling problem with the formation of manufacturing cells, simultaneously. Since the proposed model is nonlinear, a linearization method is applied to gain optimal solution when the model is solved using direct implementation of mixed integer programming. A new genetic algorithm (GA) is also proposed to solve the resulted model for large-scale problems. We examine the performance of the proposed method using the direct implementation and the proposed GA method. The results indicate that the proposed GA approach could provide efficient assembly and product structure for real-world size problems

    Effect of selegiline on the hippocampal ischemia-reperfusion injuries and cognitive impairments following global ischemia in male rats

    Get PDF
    Introduction: Selegiline, a selective monoamine oxidase type B inhibitor, has been shown to have neurotrophic and anti-apoptotic properties and to protect neurons in experimental models of cerebral ischemia. The aim of this study was to investigate whether selegiline could enhance cognitive and functional recovery in stroke disease. Selegiline is a drug that has demonstrated antioxidant and neuroprotective effects, as documented in the permanent middle cerebral artery occlusion model in rats. Widely used in the treatment of Parkinson's disease and in recent studies showed anti-inflammatory and anti-apoptotic properties. It has been shown to reduce total brain damage after transient hypoxia– Ischemia. Methods and Results: The male rats were randomized into four groups: Control groups, Control + Selegiline (2 mg/kg), stroke induction groups and stroke+ Selegiline (2 mg/kg). Selegiline was gavaged after 4 days from beginning of the investigation. In this regard, we tested whether 1) Administration of selegiline is able to inhibit abnormality behaviors related to global ischemia in Male Rats 2) Behavioral changes are associated with mitochondrial dysfunction in the hippocampus and 3) Administration of selegiline is able to alter immune-inflammatory factors in the hippocampus. Therefore, using valid and qualified behavioral tests for the assessment of stroke like behaviors such as novel object recognition test (NOR) were used for confirmation of stroke induction in rats. Then, animals were sacrificed and hippocampi were dissected out and stored at -80 °C. The samples were divided into two different groups; first set of samples were used for preparation of tissue homogenate, on which measurement of oxidative stress parameters and nitrite levels were performed. The second set of samples were fixed in 10% formalin, sectioned, and stained with hematoxylin and eosin (H&E) for pathological evaluations. The statistical analysis showed a significant improvement in most neuropsychological tests after two weeks in the study group. Conclusions: Data on experimental models of cerebral ischemia have suggested a marked activation of the nigrostriatal dopaminergic system by selegiline that might contribute to the protection against ischemia-induced neurodegeneration

    A review of reduction methods of aflatoxin

    Get PDF
    Food contamination with aflatoxins, a secondary metabolite produced by filamentous fungi, is a fundamental subject in food safety for human. Therefore, especial attention should be dedicated about contamination of animal feed and transfer to human food chain by contaminated livestock products. The promising approach for controlling aflatoxins in food is prevention of fungi growth. However, practically this method is not successful; therefore, alternative techniques are needed to eliminate these toxins from consumed products in human and animals. In present study, four phrases used as key words were “aflatoxin, reducing methods, food and feed “by databases including Elsevier, Scopus, PubMed, and Google Scholar. After reviewing 83 articles, 59 studies were selected; these papers were published between 1960 -2014 for recent review. Therefore, it was decided to collect and review the common and usual methods for decreasing or deletion of deterioration of Aflatoxin in livestock feed and human food including physical, chemical and biological methods

    current state of poison control centers in Pakistan and the need for capacity building.

    Get PDF
    Background: Chemical exposure is a major health problem globally. Poison control centers (PCCs) play a leading role both in developed and developing countries in the prevention and control of poisonous chemical exposures. In this study, we aimed to assess the current state of PCCs in Pakistan and highlight capacity building needs in these centers. Methods: A cross-sectional survey of the two registered PCCs was done during August – December 2011. Necessary services of the PCCs were evaluated and the data were recorded on a predesigned checklist. Results: Both PCCs are affiliated to a tertiary care hospital. Clinical services to poisoned patients were available 24 hours a day / 7 days a week. Information on common local products was available to poison center staff. Both centers were involved in undergraduate and post graduate teaching. Telephone poison information service was not available in either of centers. There was a limited capacity for qualitative and analytical toxicology. Common antidotes were available. There were limited surveillance activities to capture toxic risks existing in the community and also a deficiency was observed in chemical disaster planning. Conclusion: PCCs in Pakistan need capacity building for specialized training in toxicology, toxicovigilance, chemical disaster planning, analytical laboratory tests and telephone service for consultation in poisoning cases

    Tropisetron attenuated the anxiogenic effects of social isolation by modulating nitrergic system and mitochondrial function.

    Get PDF
    Abstract BACKGROUND: Early social isolation stress (SIS) is associated with the occurrence of anxiety behaviors. It seems interaction between the nitrergic system and mitochondrial function plays a role in mediating the anxiety-like behaviors. In this study, we aimed to investigate the anxiolytic effects of tropisetron in animal model of SIS and we try to illustrate the possible role of nitrergic system and mitochondrial function. METHODS: We applied early social isolation paradigm to male NMRI mice. Animals treated with various doses of tropisetron, nitric oxide agents or their combination and anxiety-like behaviors of animals were assessed using valid behavioral tests including elevated plus maze (EPM), open-field test (OFT) and hole-board test (HBT) in their adulthood. Effects of housing conditions and drug treatments on the mitochondrial function were investigated in the hippocampus by assessing the ATP, GSH, ROS and nitrite levels. RESULTS: Anxiogenic effects of early SIS were assessed in the EPM, OFT, and HBT. Also, SIS disrupted mitochondrial function and caused oxidative stress in the hippocampus of stressed animals. Tropisetron showed an anxiolytic effect in the stressed mice. Also, these effects were mediated by nitrergic system by affecting mitochondrial function and modulating the oxidative stress. L-arginine, a nitric oxide precursor, abolished the anxiolytic effects of tropisetron in the behavioral tasks and blocked the protective effects of it against mitochondrial and oxidative challenge. CONCLUSIONS AND GENERAL SIGNIFICANCE: Our results demonstrated tropisetron attenuated the anxiogenic effects of SIS by mitigation of the negative effects of nitric oxide on mitochondrial functio

    Anxiety- and Depressive-Like Behaviors are Associated with Altered Hippocampal Energy and Inflammatory Status in a Mouse Model of Crohn’s Disease

    Get PDF
    Abstract—Depression and anxiety are common comorbid disorders observed in patients with inflammatory bowel disease (IBD). Increasing line of evidence indicates that immune-inflammatory responses are involved in cooccurrence of mood disorders and IBD. However, the mechanisms through which immune-inflammatory pathways modulate this comorbidity are not yet understood. This study investigated the role of innate immunity in the development of behavioral abnormalities associated with an animal model of Crohn’s disease (CD). To do this, we induced colitis in male adult mice by intrarectal (i.r.) injection of DNBS (Dinitrobenzene sulfonic acid). After 3 days, we performed behavioral tests for anxiety- and depressive-like behaviors as well as tissue collection. Our results showed that DNBS-induced colonic inflammatory responses were accompanied by infiltration of inflammatory cells, and increased expression of genes involved in toll-like receptor signaling pathway in intestinal tissue. Furthermore, the DNBS-treated mice showed depressive- and anxiety-like behaviors which were associated with increased expression of the inflammatory genes and abnormal mitochondrial function in the hippocampus. These results suggest that peripheral inflammation is able to increase the transcriptional level of the genes in tolllike receptor pathway, induces abnormal mitochondrial function in the hippocampus, and these negative effects may be involved in the co-occurrence of anxiety and depression in early stages of CD. � 2017 IBRO. Published by Elsevier Ltd. All rights reserved

    CHANGES IN THE TREATMENT PLANS OF GLAUCOMA PATIENTS IN A REAL-WORLD SITUATION

    Get PDF
    OBJECTIVE: To determine the changes in glaucoma prescriptions during a single visit in real-world situation at Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan. METHODS: This cross-sectional descriptive study was conducted at Glaucoma Department of Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan from September 1st, 2015 to February 29th, 2016 after the ethical approval. Of total 876 consecutive participants, 868 were included in the study. Complete ocular examination was carried out for each subject including intraocular pressure (IOP) by Goldmann, visual field and nerve fiber analysis if it was scheduled. Ocular and systemic co-morbidities as well as ocular surgeries were also noted. Number of topical medications including anti-glaucoma and other drugs were recorded before and after their visit. The changes in anti-glaucoma medications were then categorized as unchanged, changed, added or deleted. The results were analyzed via SPSS version-24. RESULTS: A total 1600 eyes of 868 patients were included in this study. Out of 868 patients, 507 (58.41%) were males and 291 (33.52%) were in 61-70 years age group. Majority of patients (n=680/868: 78.34%) had open-angle glaucoma. Out of 1600 eyes studied, 574 (35.87%) had moderate and 556 (34.75%) had severe stage of glaucomatous optic neuropathy. During single visit, glaucoma-related prescriptions were unchanged, changed, added and deleted in 618/868 (71.20%), 84/868 (9.68%), 95/868 (10.94%) & 71/868 (8.18%) patients respectively. In our study, 911/1600 (56.94%) eyes achieved target IOP ≤14 mmHg. CONCLUSION: In real-world situation, most of our glaucoma patients were stable and required no changes to their prescriptions in single visit

    Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice

    Get PDF
    Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2 mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24 h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A2 (cPLA2) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation
    corecore