DOCSLIB.ORG

THE BIOTECHNOLOGY of EFFLUENT-GROWN Spirulina, and APPLICATION in AQUACULTURE NUTRITION

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
THE BIOTECHNOLOGY of EFFLUENT-GROWN Spirulina, and APPLICATION in AQUACULTURE NUTRITION THE BIOTECHNOLOGY OF EFFLUENT-GROWN Spirulina, AND APPLICATION IN AQUACULTURE NUTRITION THESIS Submitted in fulfilment of the requirements for the degree of MASTER OF SCIENCE (BIOTECHNOLOGY) Rhodes University Grahamstown by BRENTON ASHLEY MAART November 1992 TABLE OF CONTENTS ABSTRACT I LIST OF FIGURES IV LIST OF TABLES V1l1 CHAPTER 1 SALINITY AND ALGAL BIOTECHNOLOGY PART A MICROALGAE AND SALINE WASTEWATER 1 PARTB The Biotechnology of Spirulina PRODUCTION 10 CHAPTER 2 RESEARCH PROGRAMME Spirulina AND TANNERY WASTEWATER 27 CHAPTER 3 OCCURRENCE OF SpirulilUl IN TANNERY EFFLUENT 3.1 INTRODUCTION 30 3.2 RESEARCH OBJECTIVES 32 3.3 MATERIALS AND METHODS 33 3.4 RESULTS 34 3.5 DISCUSSION 43 CHAPTER 4 HARVESTING AND PROCESSING 4.1 INTRODUCTION 49 4.2 RESEARCH OBJECTNES 55 4.3 MATERIALS AND METHODS 55 4.4 RESULTS 61 4.5 DISCUSSION 62 CHAPTER 5 CHEMICAL COMPOSITION 5.1 INTRODUCTION 65 5.2 RESEARCH OBJECTIVES 68 5.3 MATERIALS AND METHODS 69 5.4 RESULTS 75 5.5 DISCUSSION 79 CHAPTER 6 TOXICOLOGICAL EVALUATION OF Spirulina BIOMASS 6.1 INTRODUCTION 84 6.2 RESEARCH OBJECTIVES 92 6.3 MATERIALS AND METHODS 92 6.4 RESULTS 98 6.5 DISCUSSION 112 CHAPTER 7 FEEDING Spirulina TO THE SOUTH AFRICAN ABALONE, HaIiotis midae 7.1 INTRODUCTION 120 7.2 RESEARCH OBJECTIVES 126 7.3 MATERIALS AND METHODS 126 7.4 RESULTS 131 7.5 DISCUSSION 136 CHAPTER 8 FEEDING Spirulina TO THE RAINBOW TROUT, Oncorhynchus mykiss 8.1 INTRODUCTION 141 8.2 RESEARCH OBJECTIVES 149 8.3 MATERIALS AND METHODS 150 8.4 RESULTS 157 8.5 DISCUSSION 165 CHAPTER 9 CONCLUSIONS AND RECOMMENDATIONS 172 REFERENCES 179 ACKNOWLEDGEMENTS 205 APPENDIX I 207 APPENDIX II 208 ABSTRACT The biotechnology of production and utilisation of the cyanobacterium Spirulina has been well documented. Research has centred mainly on application in human and animal nutrition, and has been motivated by the high protein, vitamin, fatty acid and growth factor contents. The main obstacle in realising the full potential of this feed source has been the high production costs associated with its mass culture in defined media. The observation of blooms of Spirulina in tannery effluent evaporation ponds in Wellington, South Africa, prompted this investigation into the harvesting, and nutritional and toxicological evaluation of this potentially low-cost production system, with the ultimate aim of using the product in aquaculture rations. An investigation of the chemical gradient along the evaporation cascade showed a positive correlation between the prevailing chemical conditions and the dominant species populations. A standing crop of 9.5 tonnes/ha of Spirulina was found to be present in the latter alkaline ponds, characterised by relatively lower organic and sulphur contents. Initial harvesting of the biomass was achieved by the design, construction and implementation of a small-scale screen harvest, which yielded a 25 kg (dry weight) crop. A scale-up model was then designed, and implemented in a technical scale harvest, yielding a crop of 250 kg (dry weight). Both these harvests utilised the bloom of surface-autoflocculated biomass. Concentrated cell slurries were sun-dried on muslin beds, and milled to a coarse powder. An evaluation of the harvest revealed a chemical content similar to other published reports of defined media cultures, with the exception of the protein and amino acid contents. The observed lower levels of the latter two are almost certainly due to the sun-drying method employed, known to reduce the protein content due to thermal denaturation. Legislation demands the strict toxicological evaluation of new protein sources, and because of the effluent-nature of the growth medium of this source of Spirulina, its viability lies only in the application as an animal feed or supplement. A range of toxicological tests were I chosen that were targeted to elucidate the possible toxicological constraints of this effluent­ grown source of protein in animal nutrition. The nucleic acid and pesticide contents of the harvested biomass were within the prescribed safety ranges. Atomic absorption showed minimal accumulation of minerals and heavy metals from the effluent. A bioassay with the brine shrimp Anemia salina showed that the biomass contained no toxicologically active water-soluble components. A short term feeding trial with new-born chicks showed that supplementation with Spirulina had no effect on the growth rates and feed conversion ratios of the different feeding groups. Pathological analyses showed that the liver was the only target organ to elicit a change in response to supplementation of the diets with Spirulina. A general decrease in liver weight was noted, with Cu, Ca, Fe and Zn being significantly accumulated. A histopathological examination however, showed no cellular and functional aberration from the control animals. The toxicological analyses gave the preliminary safe go-ahead for the evaluation of effluent­ grown Spirulina in aquaculture nutrition. The South African abalone Haliotis midae, and the rainbow trout Oncorhynchus mykiss were chosen as representative species of edible cultured organisms. The technology for the culture of the perlemoen abalone is being established in South Africa, with the main area of research being the development of an artificial diet for high density culture. A 40 day growth trial demonstrated that lower concentrations of Spirulina supplemented to an agar-based fishmeal diet resulted in growth rates and feed conversion ratios similar to the control fishmeal and purified-casein diets, and thus has application potential in the nutrition of this high-cost marine delicacy. The aquaculture technology of freshwater rainbow trout is already well established. An eight week feeding trial with various concentrations of Spirulina showed that this effluent-grown protein source can partially replace fishmeal in semi-purified diets. Fish fed Spirulina did not exhibit decisive manifestations of toxicity, as determined in a histopathological study. In addition, Spirulina supplementation resulted in enhanced colouration of the skin and flesh, which may have implications in the aesthetic marketing of this sought-after table fish. II The primary aim of this preliminary investigation thus concerned the determination of the biotechnological potential of this effluent-source of Spirulina. A technology transfer from the economically unfeasible defined-media culture was implemented. This project is ultimately aimed as a contribution towards the treatment of tannery wastewater, by the removal of contaminants from the effluent in the form of organic biomass. III LIST OF FIGURES Figure 3.1 Plan view of the evaporation ponding cascade at WTC, Wellington. Effluent is pumped from the factory to pond 1, flows to pond 5, where it is pumped to pond 6, and then concentrated by evaporation through to ponds 10 & 11. At certain times, ponds A and B remain stagnant, while the other nonds are used in the evaporation cascade. Figure 3.2 Red colour observed in the initial ponds in the effluent-treatment cascade. The colour is caused by the predominant halobacteria. Figure 3.3 Rafts of Spirulina in Pond D in the evaporation ponding cascade. Figure 3.4 Spirulina sp. in ponded effluent. Note the presence of the coexisting filamentous cyanobacterium, Anabaena spp. Figure 4.1 Diagrammatic representation of the small-scale screen harvester used for the concentration of Spirulina (holding reservoir, collecting reservoir, stilling baffle, screen, lateral supports, front supports, running groove). Figure 4.2 On-site operation of the screen harvester in a small-scale harvest of Spirulina biomass from tannery effluent. Figure 4.3 Side, plan and front elevation design of the technical-scale screen harvester for use at WTC, Wellington. Figure 4.4 Technical-scale harvest of the Spirulina biomass in pond D at WTC, Wellington. Figure 4.5 Sun-drying the Spirulina biomass on muslin beds. Figure 6.1 Survival of A. salina nauplii larvae at 24 hrs, after exposure to varying concentrations of Spirulina biomass. Figure 6.2 Survival of A.salina nauplii larvae at 12 and 24 hrs, after exposure to varying concentrations of lysed Spirulina biomass. Figure 6.3 Feed Consumption of the three feeding groups of chickens. Figure 6.4 Growth rates of the three feeding groups of chickens. Figure 6.5 Feed Conversion Ratios (FCR) for the three different feeding groups. Figure 6.6 Wet weight analysis of the hearts, livers, kidneys and spleens from the three chicken feeding groups. IV Figure 6.7 Dry weight analysis of the hearts, livers, kidneys and spleens from the three chicken feeding groups. Figure 6.8 Mineral and metal content of the dried liver samples as determined by atomic absorption spectroscopy. Figure 6.9 Sections of the hearts from the three chicken feeding groups (mag. - l00X). The myocardial fibres in all the examined samples spanning the three feeding groups appear to be faintly granular, but the change is mild and does not appear to be significant. No other significant lesions are noticeable in any of the specimens. (Myofibrils; Nucleus) Figure 6.10 Sections of the livers from the three chicken feeding groups (mag - 160X). There are no significant morphological lesions in the control and 10% feeding groups. One specimen from the 50% feeding group, however, exhibited atrophy of the hepatocyte chords, but this condition was not noted in any of the other specimens examined. Another specimen was shown to contain a few urate crystals in the lumen of some of the cortical tubes. This may be due to dehydration caused by the high concentration of NaCI in the biomass. Again, this condition was not noted in any of the other examined specimens. (Nuclei; Hepatocytes) Figure 6.11 Sections of the kidneys from the three chicken feeding groups (mag. = 160X). Generally, there are no significant lesions in any of the feeding groups. Some of the individual renal tubular epithelial cells in the 50% feeding group exhibit slight degeneration. This, however, is probably due to mild dehydration caused by the high NaCI concentration in the Spirulina biomass.
Load more

Recommended publications
  • Endogenous Metabolites: JHU NIMH Center Page 1
    S. No. Amino Acids (AA) 24 L-Homocysteic acid 1 Glutaric acid 25 L-Kynurenine 2 Glycine 26 N-Acetyl-Aspartic acid 3 L-arginine 27 N-Acetyl-L-alanine 4 L-Aspartic acid 28 N-Acetyl-L-phenylalanine 5 L-Glutamine 29 N-Acetylneuraminic acid 6 L-Histidine 30 N-Methyl-L-lysine 7 L-Isoleucine 31 N-Methyl-L-proline 8 L-Leucine 32 NN-Dimethyl Arginine 9 L-Lysine 33 Norepinephrine 10 L-Methionine 34 Phenylacetyl-L-glutamine 11 L-Phenylalanine 35 Pyroglutamic acid 12 L-Proline 36 Sarcosine 13 L-Serine 37 Serotonin 14 L-Tryptophan 38 Stachydrine 15 L-Tyrosine 39 Taurine 40 Urea S. No. AA Metabolites and Conjugates 1 1-Methyl-L-histidine S. No. Carnitine conjugates 2 2-Methyl-N-(4-Methylphenyl)alanine 1 Acetyl-L-carnitine 3 3-Methylindole 2 Butyrylcarnitine 4 3-Methyl-L-histidine 3 Decanoyl-L-carnitine 5 4-Aminohippuric acid 4 Isovalerylcarnitine 6 5-Hydroxylysine 5 Lauroyl-L-carnitine 7 5-Hydroxymethyluracil 6 L-Glutarylcarnitine 8 Alpha-Aspartyl-lysine 7 Linoleoylcarnitine 9 Argininosuccinic acid 8 L-Propionylcarnitine 10 Betaine 9 Myristoyl-L-carnitine 11 Betonicine 10 Octanoylcarnitine 12 Carnitine 11 Oleoyl-L-carnitine 13 Creatine 12 Palmitoyl-L-carnitine 14 Creatinine 13 Stearoyl-L-carnitine 15 Dimethylglycine 16 Dopamine S. No. Krebs Cycle 17 Epinephrine 1 Aconitate 18 Hippuric acid 2 Citrate 19 Homo-L-arginine 3 Ketoglutarate 20 Hydroxykynurenine 4 Malate 21 Indolelactic acid 5 Oxalo acetate 22 L-Alloisoleucine 6 Succinate 23 L-Citrulline 24 L-Cysteine-glutathione disulfide Semi-quantitative analysis of endogenous metabolites: JHU NIMH Center Page 1 25 L-Glutathione, reduced Table 1: Semi-quantitative analysis of endogenous molecules and their derivatives by Liquid Chromatography- Mass Spectrometry (LC-TripleTOF “or” LC-QTRAP).
    [Show full text]
  • Opposing Effects of Dehydroepiandrosterone And
    European Journal of Endocrinology (2000) 143 687±695 ISSN 0804-4643 EXPERIMENTAL STUDY Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells M O Canning, K Grotenhuis, H J de Wit and H A Drexhage Department of Immunology, Erasmus University Rotterdam, The Netherlands (Correspondence should be addressed to H A Drexhage, Lab Ee 838, Department of Immunology, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Email: [email protected]) Abstract Background: Dehydroepiandrosterone (DHEA) has been suggested as an immunostimulating steroid hormone, of which the effects on the development of dendritic cells (DC) are unknown. The effects of DHEA often oppose those of the other adrenal glucocorticoid, cortisol. Glucocorticoids (GC) are known to suppress the immune response at different levels and have recently been shown to modulate the development of DC, thereby influencing the initiation of the immune response. Variations in the duration of exposure to, and doses of, GC (particularly dexamethasone (DEX)) however, have resulted in conflicting effects on DC development. Aim: In this study, we describe the effects of a continuous high level of exposure to the adrenal steroid DHEA (1026 M) on the generation of immature DC from monocytes, as well as the effects of the opposing steroid DEX on this development. Results: The continuous presence of DHEA (1026 M) in GM-CSF/IL-4-induced monocyte-derived DC cultures resulted in immature DC with a morphology and functional capabilities similar to those of typical immature DC (T cell stimulation, IL-12/IL-10 production), but with a slightly altered phenotype of increased CD80 and decreased CD43 expression (markers of maturity).
    [Show full text]
  • Fluorinated Analogues of Glutamic Acid and Glutamine R
    γ-Fluorinated analogues of glutamic acid and glutamine R. Dave, B. Badet, Patrick Meffre To cite this version: R. Dave, B. Badet, Patrick Meffre. γ-Fluorinated analogues of glutamic acid and glutamine. Amino Acids, Springer Verlag, 2003, 24 (3), pp.245-261. 10.1007/s00726-002-0410-9. hal-02002676 HAL Id: hal-02002676 https://hal.archives-ouvertes.fr/hal-02002676 Submitted on 11 Feb 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. γ-Fluorinated analogues of glutamic acid and glutamine Review Article 1 2 1 R. Dave , B. Badet , and P. Meffre 1 UMR 7573-C.N.R.S., ENSCP, Paris, France 2 UPR 2301-CNRS, ICSN, Gif-sur-Yvette, France Summary. γ-Fluorinated analogues of glutamic acid and glutamine N-bromosuccinimide; NFSi, N-fluorobenzenesulfonimide; NMR, are compounds of biological interest. Syntheses of such compounds nuclear magnetic resonance; 2-PrOH, isopropanol; PTSA, p- are extensively reviewed in this article. 4-Fluoroglutamic acid toluenesulfonic acid; TCDI, thiocarbonyldiimidazole; TEMPO, was prepared as a mixture of racemic diastereomers by Michael 2,2,6,6-tetramethyl piperidine-1-oxyl; TFA, trifluoroacetic acid. reaction, inverse-Michael reaction or by electrophilic / nucleophilic fluorination.
    [Show full text]
  • The Role of Glutamine in the Complex Interaction Between Gut Microbiota and Health: a Narrative Review
    International Journal of Molecular Sciences Review The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review 1, , 1 1, 1 Simone Perna * y , Tariq A. Alalwan , Zahraa Alaali y , Tahera Alnashaba , Clara Gasparri 2, Vittoria Infantino 3 , Layla Hammad 1, Antonella Riva 4, Giovanna Petrangolini 4 , Pietro Allegrini 4 and Mariangela Rondanelli 5,6 1 Department of Biology, College of Science, University of Bahrain, 32038 Sakhir, Bahrain; [email protected] (T.A.A.); [email protected] (Z.A.); [email protected] (T.A.); [email protected] (L.H.) 2 Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia 27100, Italy; [email protected] 3 Department of Biomedical Science and Human Oncology, University of Bari, Bari 70121, Italy; [email protected] 4 Research and Development Department, Indena SpA, 20139 Milan, Italy; [email protected] (A.R.); [email protected] (G.P.); [email protected] (P.A.) 5 IRCCS Mondino Foundation, Pavia 27100, Italy; [email protected] 6 Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, Pavia 27100, Italy * Correspondence: [email protected] or [email protected]; Tel.: +973-39-37-99-46 The two authors contributed equally to this work. y Received: 21 August 2019; Accepted: 20 October 2019; Published: 22 October 2019 Abstract: The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy of glutamine and its effect on gut microbiota.
    [Show full text]
  • Effects of Amanita Muscaria Extract on Different in Vitro Neurotoxicity
    Food and Chemical Toxicology 132 (2019) 110687 Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox Effects of Amanita muscaria extract on different in vitro neurotoxicity models at sub-cellular and cellular levels T Magdalena Kondeva-Burdinaa,*, Maria Voynovaa, Aleksandar Shkondrovb, Denitsa Aluania, Virginia Tzankovaa, Ilina Krastevab a Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000, Sofia, Bulgaria b Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000, Sofia, Bulgaria ARTICLE INFO ABSTRACT Keywords: Muscimol is the main compound found in Amanita muscaria. Several studies have proven that muscimol has Amanita muscaria suppressive effects on essential tremor, without impairing speech and coordination. The effects of muscimol in Isolated rat brain microsomes Parkinson-affected patients is also described in a number of studies. These studies describe the free radical Synaptosomes scavenging and antioxidant activity of the mushroom extract. We have evaluated the possible neuroprotective Mitochondria effects of a standardized extract from A. muscaria, containing high amounts of muscimol, on different models of Neuroblastoma cell line SH-SY5Y neurotoxicity in rat brain microsomes, mitochondria, synaptosomes as well as on neuroblastoma cell line SH- Neuroprotection ff Human recombinant monoaminoxidase-B SY5Y. The possible inhibitory e ect on human recombinant monoaminoxidase-B (hMAOB) enzyme was also enzyme studied. The extract revealed statistically significant neuroprotective effects on the in vitro neurotoxicity models and no inhibitory activity on hMAOB. 1. Introduction without influencing the speech and movements of the patients (Ferreira et al., 2007).
    [Show full text]
  • DHEA), the Most Abundant Sex Steroid, Is Primarily Secreted by the Adrenal Gland and a Precursor Hormone Used by Athletes for Performance Enhancement
    Int. J. Med. Sci. 2016, Vol. 13 730 Ivyspring International Publisher International Journal of Medical Sciences 2016; 13(10): 730-740. doi: 10.7150/ijms.16132 Research Paper Dehydroepiandrosterone Supplementation Combined with Whole-Body Vibration Training Affects Testosterone Level and Body Composition in Mice Wen-Chyuan Chen 1,2, Yi-Ming Chen 1,3, Chi-Chang Huang 3, and Yen-Dun Tzeng4 1. Center for General Education, Chang Gung University of Science and Technology, Taoyuan 33301, Taiwan; 2. Department of Otorhinolaryngology-Head and Neck Surgery, Sleep Center, Linkou-Chang Gung Memorial Hospital, Taoyuan 33301, Taiwan. 3. Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan 33301, Taiwan; Emails: [email protected] (Y.-M.C.); 4. Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, 813 Kaohsiung, Taiwan. Corresponding author: Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung City 81362, Taiwan (Y.-D.T.). Tel.: +886-7-3422121 (ext. 3008) (Y.-D.T.). Electronic addresses: [email protected] (Y.-D.T.). © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. Received: 2016.05.11; Accepted: 2016.08.19; Published: 2016.09.16 Abstract Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults.
    [Show full text]
  • Pigments of Fly Agaric (Amanita Muscaria) Florian Stintzinga,C,* and Willibald Schliemannb
    Pigments of Fly Agaric (Amanita muscaria) Florian Stintzinga,c,* and Willibald Schliemannb a Institute of Food Science and Biotechnology, Section Plant Foodstuff Technology, Hohenheim University, August-von-Hartmann-Str. 3, D-70599 Stuttgart, Germany b Department of Secondary Metabolism, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany c Present address: WALA Heilmittel GmbH, Dorfstraße 3, D-73087 Bad Boll/Eckwälden, Germany. E-mail: [email protected] * Author for correspondence and reprint requests Z. Naturforsch. 62c, 779Ð785 (2007); received July 2/August 3, 2007 The complex pigment pattern of fly agaric (Amanita muscaria) cap skins has been studied by LC-DAD and mass spectrometry. Among the betaxanthins the corresponding derivatives of serine, threonine, ethanolamine, alanine, Dopa, phenylalanine and tryptophan are re- ported for the first time to contribute to the pigment pattern of fly agarics. Betalamic acid, the chromophoric precursor of betaxanthins and betacyanins, muscaflavin and seco-dopas were also detected. Furthermore, the red-purple muscapurpurin and the red muscarubrin were tentatively assigned while further six betacyanin-like components could not be structur- ally allocated. Stability studies indicated a high susceptibility of pigment extracts to degrada- tion which led to rapid colour loss thus rendering a complete characterization of betacyanin- like compounds impossible at present. Taking into account these difficulties the presented results may be a starting point for a comprehensive characterization of the pigment composi- tion of fly agarics. Key words: Amanita muscaria, Fly Agaric, Betalains Introduction Recent reviews on betalains in general (Zry¨d and Christinet, 2004) and on the chemistry of The reddish colour of the cap skin of the toad- natural products of A.
    [Show full text]
  • Pharmacological Studies on a Locust Neuromuscular Preparation
    J. Exp. Biol. (1974). 6i, 421-442 421 *&ith 2 figures in Great Britain PHARMACOLOGICAL STUDIES ON A LOCUST NEUROMUSCULAR PREPARATION BY A. N. CLEMENTS AND T. E. MAY Woodstock Research Centre, Shell Research Limited, Sittingbourne, Kent {Received 13 March 1974) SUMMARY 1. The structure-activity relationships of agonists of the locust excitatory neuromuscular synapse have been reinvestigated, paying particular attention to the purity of compounds, and to the characteristics and repeatability of the muscle response. The concentrations of compounds required to stimu- late contractions of the retractor unguis muscle equal in force to the neurally evoked contractions provided a measure of the relative potencies. 2. Seven amino acids were capable of stimulating twitch contractions, glutamic acid being the most active, the others being analogues or derivatives of glutamic or aspartic acid. Aspartic acid itself had no excitatory activity. 3. Excitatory activity requires possession of two acidic groups, separated by two or three carbon atoms, and an amino group a to a carboxyl. An L-configuration appears essential. The w-acidic group may be a carboxyl, sulphinyl or sulphonyl group. Substitution of any of the functional groups generally causes total loss of excitatory activity, but an exception is found in kainic acid in which the nitrogen atom forms part of a ring. 4. The investigation of a wide variety of compounds revealed neuro- muscular blocking activity among isoxazoles, hydroxylamines, indolealkyl- amines, /?-carbolines, phenazines and phenothiazines. No specific antagonist of the locust glutamate receptor was found, but synaptic blocking agents of moderately high activity are reported. INTRODUCTION The study of arthropod neuromuscular physiology has been impeded by the lack of an antagonist which can be used to block excitatory synaptic transmission by a specific postsynaptic effect.
    [Show full text]
  • The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases Β-Amyloid Protein Levels
    ORIGINAL CONTRIBUTION The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases ␤-Amyloid Protein Levels Yuanlin Dong, MD; Guohua Zhang, MD, PhD; Bin Zhang, MD; Robert D. Moir, PhD; Weiming Xia, PhD; Edward R. Marcantonio, MD; Deborah J. Culley, MD; Gregory Crosby, MD; Rudolph E. Tanzi, PhD; Zhongcong Xie, MD, PhD Objective: To assess the effects of sevoflurane, the most Z-VAD decreased the effects of sevoflurane on apopto- commonly used inhalation anesthetic, on apoptosis and sis and A␤. Sevoflurane-induced caspase-3 activation was ␤-amyloid protein (A␤) levels in vitro and in vivo. attenuated by the ␥-secretase inhibitor L-685,458 and was potentiated by A␤. These results suggest that sevoflu- Subjects: Naive mice, H4 human neuroglioma cells, and rane induces caspase activation which, in turn, en- H4 human neuroglioma cells stably transfected to ex- hances ␤-site amyloid precursor protein–cleaving en- press full-length amyloid precursor protein. zyme and A␤ levels. Increased A␤ levels then induce further rounds of apoptosis. Interventions: Human H4 neuroglioma cells stably transfected to express full-length amyloid precursor pro- Conclusions: These results suggest that inhalational an- tein were exposed to 4.1% sevoflurane for 6 hours. Mice esthetic sevoflurane may promote Alzheimer disease neu- received 2.5% sevoflurane for 2 hours. Caspase-3 acti- ropathogenesis. If confirmed in human subjects, it may vation, apoptosis, and A␤ levels were assessed. be prudent to caution against the use of sevoflurane as an anesthetic, especially in those suspected of possess- ␤ Results: Sevoflurane induced apoptosis and elevated lev- ing excessive levels of cerebral A . els of ␤-site amyloid precursor protein–cleaving en- zyme and A␤ in vitro and in vivo.
    [Show full text]
  • Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
    Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1 • Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration • Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).” • Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA (dehydroepiandrosterone).” 1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of Bone, Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and route of administration.
    [Show full text]
  • Improved Method of Administering Beta-Hydroxy
    (19) TZZ _ ¥_T (11) EP 2 512 236 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A01N 37/00 (2006.01) A61K 31/19 (2006.01) 19.10.2016 Bulletin 2016/42 (86) International application number: (21) Application number: 10838355.5 PCT/US2010/061367 (22) Date of filing: 20.12.2010 (87) International publication number: WO 2011/075741 (23.06.2011 Gazette 2011/25) (54) IMPROVED METHOD OF ADMINISTERING BETA-HYDROXY-BETA-METHYLBUTYRATE (HMB) VERBESSERTES VERFAHREN ZUR VERABREICHUNG VON BETA-HYDROXY-BETA-METHYLBUTYRAT (HMB) PROCÉDÉ AMÉLIORÉ PERMETTANT D’ADMINISTRER DU BÊTA-HYDROXY-BÊTA-MÉTHYLBUTYRATE (HMB) (84) Designated Contracting States: • NISSEN, Steve AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Ames GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Iowa 50014 (US) PL PT RO RS SE SI SK SM TR • ABUMRAD, Naji Nashville (30) Priority: 18.12.2009 US 287857 P Tennessee 37220 (US) (43) Date of publication of application: (74) Representative: Evans, Jacqueline Gail Victoria 24.10.2012 Bulletin 2012/43 Marches Intellectual Property Limited Wyastone Business Park (73) Proprietor: Metabolic Technologies, Inc. Wyastone Leys Ames, IA 50010 (US) Ganarew Monmouth NP25 3SR (GB) (72) Inventors: • RATHMACHER, John (56) References cited: Story City US-A- 4 992 470 US-A- 5 028 440 Iowa 50248 (US) US-A- 5 087 472 US-A- 6 031 000 • FULLER, John US-A1- 2004 220 266 US-A1- 2005 215 640 Zearing US-A1- 2005 215 640 Iowa 50278 (US) • BAIER, Shawn Remarks: Polk City Thefile contains technical information submitted after Iowa 50226 (US) the application was filed and not included in this specification Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • The Effects of L-Glutamate, L-Glutamine, and L-Aspartic Acid on the Amylase Production of E
    Journal of Emerging Investigators The Effects of L-glutamate, L-glutamine, and L-aspartic Acid on the Amylase Production of E. coli Transformed with pAmylase Kevin S. Liu and Brittany Franckowiak Wilde Lake High School, Howard County, MD Summary glands, hydrolyzes dietary starch into disaccharides Amylase catalyzes the hydrolysis of dietary starch into and trisaccharides. These saccharides are further oligosaccharides. In humans, amylase is produced by the converted by other enzymes to glucose and used as pancreas and salivary glands and is important in food a source of cellular energy (1). Consequently, amylase digestion. Human amylase also has broad applications for has an important role in digestion, where the secretion of therapeutic use in patients with pancreatic insufficiency, necessitating an efficient process for amylase production. amylase is vital to proper nutrient digestion and absorption E. coli transfected with human amylase cDNA can be (2, 3). Abnormal or unhealthy enzyme secretion by the used to produce amylase to fulfill these pharmaceutical pancreas can result in nutrient malabsorption and other production needs. It was reported that the production symptoms that lead to malnutrition (4). of Thermus maltogenic amylase in E. coli is enhanced by In addition to their role in digestion, amylases are also adding L-glutamate and L-glutamine. The purpose of this important ingredients in the food industry. Specifically, experiment was to determine whether the amino acids alpha and beta amylases are used in brewing beers and L-glutamate, L-glutamine, and L-aspartic acid could liquors made from starch-derived sugars. Amylases, increase human amylase expression in E. coli.
    [Show full text]