Hamburg, Universiẗat, Diss., 2001.

Hamburg, Universiẗat, Diss., 2003.

Dissertation submitted in partial compliance with the requirements for the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2010. / Provings are an essential element in the development of the homoeopathic medicine knowledge base and scope of practice. There are many South African indigenous plants and animals that can play a role in homoeopathy but need to be proved first. Several indigenous snake venoms have already been proved as homoeopathic remedies, so the proving of Dendroaspis angusticeps venom expands this particular knowledge base. Aim The aim of this study was to determine the effect of a homoeopathic dose of the venom of the Dendroaspis angusticeps on healthy individuals in order to elicit and document the resulting mental and physical symptomotology, so that it may be prescribed to those that require it based on the Law of Similars. The other aims of this study were to compare the proving symptoms of Dendroaspis angusticeps 30CH to the toxicology of Eastern Green Mamba venom and to analyze the remedy picture in relation to the doctrine of signatures. The thirtieth centesimal potency of the remedy was hypothesised to produce clearly observable signs and symptoms in provers (healthy volunteers). The symptoms obtained from the proving were also compared to the doctrine of signature analysis of Dendroaspis angusticeps to help clarify the nature of this snake and to expand the remedy picture of the substance and facilitate our understanding of the remedy in light of the toxicology of the venom and the doctrine of signatures. vii Methodology The homoeopathic proving of Dendroaspis angusticeps 30CH was carried out as a randomised, double blind, placebo-controlled trial. The proving population consisted of 30 provers. Twenty four of the provers were in the experimental group and they received the potentised snake venom. Six provers were in the control group and they received the placebo. As this was a double blind, placebo-controlled trial, neither the individuals taking part in the study nor the researcher had any knowledge of who received placebo or the active remedy. Provers were also unaware of the substance being proven or the potency in which it was prepared. Results Provers recorded their symptoms in a journal over a period of 5 weeks and were monitored regularly by the researcher. At the completion of the proving period, the researcher collected all the recorded data and each journal was assessed by the researcher to determine the suitability of the recorded symptoms. The symptoms were then translated into the language of the materia medica and the repertory and a remedy picture was formulated. Thereafter a comparison was made to the nature of the snake by means of the doctrine of signatures and the toxicology of the venom as an attempt to broaden the repertoire of our knowledge of the action of the remedy. Provers experienced a wide range of symptoms particularly on the mental and emotional spheres including feelings of powerful assertion and confidence; cheerful and excited energy; spiritual and prayerful feelings; seductive, sensual and extravagant mannerisms; desire to dance and heightened energy; clairvoyant natures and desires to be in nature as well as pronounced irritability, anger and sadness. Other symptoms included desire to be alone and withdrawn feelings; quarrelsome natures; desire to kill; deceitful ways; intolerance to injustice; poor concentration; thoughts of the past; confusion and antagonism of the will and anxious thoughts. Delusions, fears and thoughts of death also manifested in provers. There was a marked polarity of symptoms as: Anger, rage, irritability vs calmness / spirituality; Sadness / depression vs cheerfulness / joy; Poor concentration / forgetful vs mental power / mental clarity; Alone / withdrawn vs desire to be touched, caressed; and Prostration, exhaustion vs energetic. On the physical sphere there were marked symptoms produced in the head area with a wide range of headaches. Eye symptoms were also vast in the inflammation, heaviness and ptosis of the eyes. Throat symptoms manifested as pharyngitis and sore throat. Toxicological symptoms included vertigo, ptosis, pain in different areas, inflammation, vomiting, blurred vision, slurred speech, difficulty breathing and difficult swallowing. Back pain and lower back pain were also key symptoms. Sleep difficulties and sleepiness were experienced by provers. Dream symptoms were the most prevalent in this proving. Dreams were repetitive in provers in the dreams of changing places and being in many places and unfamiliar places. There were marked dreams of sexuality, death, spirituality, friendships, colours, snakes, weddings, fighting and killings and past recollections. Conclusion Dendroaspis angusticeps 30CH thus did produce clearly observable signs and symptoms in healthy volunteers as hypothesised. The correlation of the proving symptoms to the toxicology of the venom and the doctrine of signatures also illustrated the themes of this remedy and aided in development of the remedy picture for this new addition to the knowledge base of indigenous South African substances and their homoeopathic application. / M

The venom of cone snails is a potent cocktail of peptides, proteins, and other small molecules. Several of the peptides (conopeptides and conotoxins) target ion channels and receptors and have proven useful as biochemical probes or pharmaceutical leads. In this study, the venom of a fish-hunting cone snail, Conus purpurascens was analyzed for intraspecific variability; α-conotoxins from the venom were isolated by high performance liquid chromatography, identified by mass spectrometry and nuclear magnetic resonance, and tested in a electrophysiological assay in Drosophila melanogaster; the effects of diet change on venom composition was investigated. It has been determined that each specimen of C. purpurascens expresses a distinct venom, resulting in the expression of more than 5,000 unique conopeptides across the species. α- conotoxin PIA was shown to inhibit the Dα7 nicotinic acetylcholine receptor. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Les venins issus d’animaux sont des mélanges complexes de substances toxiques ou non qui sont utilisées pour se défendre contre des prédateurs et/ou pour chasser. Le venin est une solution contenant de nombreux composés avec une part prédominante pour les protéines et les peptides. Le venin d’un seul animal peut contenir plusieurs centaines de substances différentes. Les peptides dérivés du venin peuvent cibler des récepteurs membranaires et des canaux ioniques avec une grande affinité et une haute spécificité. Les animaux venimeux les plus connus sont les serpents, les scorpions et les araignées, et leurs toxines sont largement utilisés dans la recherche comme outils moléculaires et pour le développement des nouveaux traitements. Par conséquent, les venins d’animaux sont des sources naturelles extrêmement riches de découverte de molécules biologiquement actives. Dans ces études, nous avons criblé le venin du serpent égyptien Walterinnesia aegyptia pour l’identification de novo de peptides capables d’activer la motilité des spermatozoïdes in vitro des souris OF1. La Spermatin et X sont deux peptides de 57 et 63 acides aminés respectivement, isolés du venin du Walterinnesia aegyptia par la technique de séparation RP-HPLC suivie par la chromatographie échangeuse de cations. La spermatin et l’actiflagelin sont deux activateurs de la motilité spermatique des souris OF1. La spermatin a été séquencé par séquençage de novo en utilisant i) la digestion des peptides par des enzymes protéases comme la trypsine, la chymotrypsine et la protéase V8, et ii) les techniques de spectrométrie de masse TOF/TOF MS/MS et LC-ESI-QTOF MS/MS. Par contre, c’est la complémentarité entre le séquençage de novo, la dégradation d’Edman et les analyses ESI MS/MS qui a permis l’identification de la séquence de l’actiflagelin. Il semble dès lors que la spermatin et l’actiflagelin peuvent être utilisés comme outils pharmacologiques pour diminuer le taux d’infertilité. De l’autre côté, la maurocalcine (MCa) est un peptide de 33 résidus issu du venin du scorpion tunisien Scorpio maurus palmatus. La MCa est un activateur des récepteurs de ryanodine (RyR1) des muscles squelettiques. Elle stimule fortement la liaison du [³H]-ryanodine aux RyR1 et assure le relâchement du calcium intracellulaire des vésicules du réticulum sarcoplasmique (RS). Différents mutants de la MCa ont été utilisés et les résultats montrent que l’Arg24 joue un rôle critique dans la liaison de la MCa aux RyR1 ou tout au moins dans son impact fonctionnel. D’autres mutations de la MCa sont capables de modifier la liaison du [³H]-ryanodine aux RyR1 mais avec une plus faible efficacité que la séquence sauvage. De plus, la MCa est capable de franchir la membrane plasmique et elle est considérée comme un peptide de pénétration cellulaire. Ici, nous avons montré que la MCa est un substrat de la protéine kinase A in vitro suite à la phosphorylation du résidu Thr26. Nous avons aussi démontré que la MCa P-Thr26 inverse l’effet de la MCa. La MCa P-Thr26 inhibe la liaison du [³H]-ryanodine aux RyR1 des muscles squelettiques du lapin et elle est incapable de favoriser la libération du calcium des vésicules du RS. Alors, la MCa peut être utilisée pour le développement des analogues résistants à la phosphatase. Par ailleurs, nous avons étudié l’effet de l’agent réducteur dithiothreitol ou les agents oxydants le diamide et le peroxyde d’hydrogène sur la stimulation du RyR1 par la MCa ou MC E12A. La maurocalcine améliore la liaison du [³H]-ryanodine aux RyR1 des vésicules seules ou pré-incubées avec le dithiothreitol ou les agents oxydants. L’interprétation des résultats indiquent que la MCa et son mutant sont plus efficaces à activer RyR1 sous des conditions de réduction. Par ailleurs, des résultats ont montré que MCa E12A réduit significativement l’inhibition de la liaison du [³H]-ryanodine aux RyR1 induite par Mg²⁺. / Animal venoms are complex mixtures of toxic substances that are used to defend themselves against predators and / or to hunt. Venom is a solution containing many compounds, especially proteins and peptides. The venom of a single animal may contain several hundred different substances. Peptides derived from venom can target membrane receptors and ion channels with strong affinity and high specificity. The best known venomous animals are snakes, scorpions and spiders, and their toxins are widely used in research as molecular tools and for the development of new treatments. Therefore, animal venoms are an extremely rich and complex source of biologically active molecules. In these studies, we screened the venom of the Egyptian snake Walterinnesia aegyptia for the discovery of peptides able to activate sperm motility in vitro of mice OF1. Spermatin and actiflagelin are two peptides of 57 and 63 amino acids, respectively, isolated from the venom of Walterinnesia aegyptia by the RP-HPLC separation technique followed by cation exchange chromatography. Spermatin and actiflagelin are two activators of the spermatic motility of OF1 mice. Spermatin was sequenced by de novo sequencing using digestion of enzymes proteases such as trypsin, chymotrypsin and V8 protease, and further TOF / TOF MS / MS and LC-ESI-QTOF MS / MS. While the complementarity between de novo sequencing, Edman degradation and ESI MS / MS analyzes allowed the identification of the sequence of actiflagelin. Then, Spermatin and actiflagelin can be used as pharmacological tools to decrease the rate of infertility. On the other hand, maurocalcin (MCa) is a 33-residue peptide derived from the venom of the scorpion Scorpio maurus palmatus. MCa is an activator of ryanodine receptors (RyR1) of skeletal muscles. It strongly stimulates the binding of [³H]-ryanodine to RyR1 and ensures the release of intracellular calcium from the vesicles of the sarcoplasmic reticulum (SR). Different MCa mutants were used and the results showed that Arg24 plays a critical role in the binding of MCa to RyR1. Other mutations were able to alter the binding of [³H]-rhyanodine to RyR1 but with low efficiency. In addition, MCa is able to cross the plasma membrane and is considered a cell-penetrating peptide. Here, we have shown that MCa is a substrate of PKA in vitro following the phosphorylation of Thr26. We have also demonstrated that MCa P-Thr26 reverses the effect of MCa. MCa P-Thr26 inhibits the binding of [³H]-ryanodine to RyR1 from the rabbit skeletal muscle, and is unable to promote the release of calcium from the SR vesicles. Then, MCa can be used for the development of phosphatase resistant analogs.Keywords: Animal venom, Walterinnesia aegyptia, RP-HPLC, ion exchange chromatography, de novo sequencing, Spermatin, X, maurocalcine (MCa), [³H]-ryanodine, ryanodine receptors (RyR1), calcium, phosphorylation, sarcoplasmic reticulum (SR).

Yes / Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence. / European Union's Seventh Framework Programme FP7. Grant Number: 601763

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Includes bibliographical references. / 151 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The venom from the Australian brown snakes (Pseudonaja spp.) contains a strong procoagulant component that produces bleeding due to consumption of clotting factors in bite victims. Investigation of the role of phospholipid and calcium found neither was essential for activity, but calcium could shorten the clotting time. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2000