A mini dissertation submitted in partial compliance with the requirements for M.Tech.: Homoeopathy, Durban Institute of Technology, 2004. / The purpose of this investigation was to determine the effects of the thirtieth centesimal (30CH) potency of the venom of Bitis gabonica gabonica on healthy individuals in order to elucidate the total morbid symptomatology produced by the drug so that it may be prescribed by Homoeopathic practitioners according to the Law of Similars, as is required by Homoeopathic methodology. It was hypothesized that the 30CH potency of Bitis gabonica gabonica would produce clearly observable signs and symptoms in healthy Provers. / M

Thesis (M.Tech.: Homoeopathy) -Dept. of Homoeopathy, Durban Institute of Technology, 2004 1 v. (various pagings) / The purpose of this investigation was to determine the effects of the thirtieth centesimal (30CH) potency of the venom of Bitis gabonica gabonica on healthy individuals in order to elucidate the total morbid symptomatology produced by the drug so that it may be prescribed by Homoeopathic practitioners according to the Law of Similars, as is required by Homoeopathic methodology. It was hypothesized that the 30CH potency of Bitis gabonica gabonica would produce clearly observable signs and symptoms in healthy Provers.

Mini-dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Homoeopathy at the Durban Institute of Technology, 2002. / Dream provings are considered to be a new era in Homoeopathy and as such are met with a lot of scepticism. They involve getting in touch with the dynamic influence of the remedy and observing this influence on the vital force in the form of symptoms (Dam, 1998: 128). Dreams are a main focus of the proving as they are considered to be the 'royal way to the psycho-dynamic depth of the state of the remedy being proved' (Dam, 1998: 128). The motivations for their acceptance or rejection are both reasonable. To determine if they are provings that should appear in the Materia Medica and Repertory it needed to be seen if they revealed the same features of a remedy that a classical proving provides. / M

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Technikon Natal, 1999. / The purpose of this investigation was to determine the effects of the thirtieth centesimal (30 CH) potency of the venom of Bitis arietans arietans (the Puffadder) on healthy individuals in order to elucidate the totality of morbid symptoms produced by the drug, so that it may be prescribed according to the Law of Similars, as required by homoeopathic science. It was hypothesised that the 30 CH potency of Bitis arietans arietans would produce clearly observable symptoms and signs in healthy volunteers. / M

Snake envenomations are often medical emergencies and occur regularly in dogs. Snake venom contains hundreds of enzymes, proteins and peptides that assist in paralysing, killing and digesting prey, or as a defence against predators. Multiple snake venom components affect haemostasis in the victim. Inadvertent activation of coagulation may also result from expression of large amounts of tissue factor (TF) from injured tissues at the envenomation site, especially with potent cytotoxic venoms. The purpose of this study was to investigate the haemostatic functions in dogs envenomed by two South African snakes (Bitis arietans and Naja annulifera) using thromboelastography and traditional plasma-based coagulation assays. This prospective study included 18 client-owned dogs, of which nine dogs were envenomed by African puffadder and nine by snouted cobra. Blood was collected at presentation and at 24 hours post-envenomation. Complete blood count, thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin (AT) activity and C-reactive protein (CRP) and fibrinogen (Fib) concentrations were measured. Ten healthy client-owned dogs served as controls. These dogs were presented for routine ovariohysterectomy, castration or blood donation. Haematologic and haemostatic assay results at presentation were compared between groups using ANCOVA (analysis of covariance), and results over time between the puffadder and cobra groups were compared using linear mixed models at 5% significance. At presentation, the mean TEG R-time was significantly prolonged in the puffadder group when compared to the cobra and control groups (P=0.01 and 0.05, respectively). Visual appraisal of the thromboelastograms at presentation revealed that 5/9 (56%) of puffadder-envenomed dogs had hypocoagulable thromboelastograms as was demonstrated by prolonged R-time and decreased Angle (á), maximal amplitude (MA) and global clot strength (G). Despite this observation of hypocoagulability, none of the other TEG parameters (á, MA or G) were significantly decreased when compared to the cobra and control groups. This finding of hypocoagulability was surprising, because puffadder venom is cytotoxic, often inducing severe tissue necrosis and potentially leading to limb loss and disability in people. It therefore seems that certain components in puffadder venom affect the thromboelastograph by either interfering with or consuming coagulation factors, resulting in a hypocoagulable tracing. It is also possible that this is a dose-dependent effect, with only dogs with a significant amount of envenoming demonstrating this phenomenon. This effect appears to be transient, as 6/8 dogs (one fatality) envenomed by puffadders reverted to a severely hypercoagulable state at 24 hours post-envenomation. One dog was still hypocoagulable and one dog that was hypocoagulable became normocoagulable but still had a prolonged R-time. In the cobra-envenomed group hypercoagulable thromboelastograms were observed in 5/9 (56%) dogs at presentation as was demonstrated by increased MA and G. At 24 hours post-envenomation all cobra-envenomed dogs demonstrated hypercoagulable thromboelastograms. This hypercoagulability at presentation and 24 hours post-envenoming was not statistically significant between groups. This hypercoagulable state was likely due to tissue factor-activated coagulation promoted by inflammation at the envenomation site. At presentation, marked thrombocytopenia was evident in the puffadder-envenomed dogs when compared to the cobras and controls (P=0.04 and 0.001, respectively). Thrombocytopenia following puffadder envenomation has been reported in dogs and baboons. Components have been identified in puffadder venom that interfere with platelet function either by inhibiting or promoting aggregation. At 24 hours post-envenomation mean platelet count (Plt) was mildly increased compared to its value at presentation in the puffadder-envenomed dogs. There were Plt abnormalities in the cobra-envenomed dogs at presentation or at 24 hours post-envenomation. Marked leucocytosis was detected in the puffadder-envenomed dogs at presentation when compared to the cobras and controls (P=0.003 and 0.001, respectively) and was more severe at 24 hours post-envenomation when compared to the cobra group (P=0.01). Leucocytosis has been reported in different types of snake envenoming including puffadder-envenomed dogs. C-reactive protein (CRP) concentration at presentation was below the lowest detection limit for most dogs (14/18) in this study. At 24 hours post-envenoming all but two dogs (one each in the puffadder and cobra groups) had severely elevated CRP. This increase in CRP was statistically significant in both puffadder and cobra-envenomed dogs when compared to its concentration at presentation (P=0.04 and 0.001, respectively). Fibrinogen (Fib) concentration was not elevated in any envenomed dogs at presentation, but increased 24 hours post-envenoming. Although this increase was not statistically significant, an increase would suggest activation of the inflammatory response, as both Fib and CRP are positive acute phase proteins. Elevated CRP, neutrophilic leucocytosis and increases in cytokine IL-6 and IL-8 has been documented in four human patients bitten by Bothrops and Crotalus snakes (two each) in Brazil. CRP levels were low immediately post-envenoming, peaked at two days post-envenoming and dropped to within normal limits four days post-envenoming. These findings demonstrated a typical acute-phase response and it is likely that a similar acute phase response occurred after puffadder and cobra envenoming in our study. Mean antithrombin (AT) activity was mildly decreased in both the puffadder- and cobra-envenomed dogs compared to the controls (P=0.002 and 0.004, respectively), suggesting that the activation of haemostasis led to some AT consumption. Mean PT and mean aPTT were prolonged in the cobra-envenomed dogs compared to the controls (P=0.03 for both), but were within their reference intervals (RI). At 24 hours post envenomation mean haematocrit (Ht) was significantly decreased in the puffadder group compared to the cobra group (P=0.01), but was within RI. The Ht was significantly lower at 24 hours post envenomation compared to presentation values in both these groups (P<0.001 and 0.02, respectively). At presentation, marked thrombocytopenia, leucocytosis and prolonged clot initiation were common features in puffadder-envenomed dogs and were likely venom-induced. Snouted cobra-envenomed dogs were normo- to hypercoagulable at presentation. Both puffadder- and cobra-envenomed dogs equally showed hypercoagulability at 24 hours post-envenomation and this was more pronounced compared to their coagulability at presentation. TEG proved to be a useful tool to detect abnormal haemostasis in all envenomed dogs in this study. TEG also provided additional insights into certain aspects of snake envenomation (such as hypercoagulability) that has not been reported on previously and cannot be assessed using traditional coagulation assays. TEG may serve as a differentiating tool in early envenomation between these two types of snake envenoming in scenarios where the identity of the snake species involved is not known. / Dissertation (MMedVet)--University of Pretoria, 2012. / Companion Animal Clinical Studies / unrestricted

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology. 2013. / This study was a homoeopathic drug proving of Bitis atropos 30CH (derived from Berg adder venom) with a subsequent comparison of the proving symptoms to known venom toxicology and existing remedies from the materia medica, that on repertorisation, yielded the greatest similarities in the Mental, General, Physical and unique symptomatology of Bitis atropos. Methodology : The proving was carried out in the form of a double-blinded, placebo controlled trial on healthy subjects who were administered the proving substance or placebo. The resultant influence of this substance on the health of provers (i.e. symptoms produced) was recorded in journal format and formed the materia medica and ultimately the clinical indications thereof according to the Law of Similars. Twenty eight healthy consenting provers who meet the inclusion criteria (Appendix B), were randomly split into two groups, one being the experimental group comprising 22 provers, and the other a placebo control group comprising 6 provers. This was further split between the researcher and co-researcher, each responsible for 11 provers receiving verum and 3 receiving placebo. The researchers and the individual provers were unaware of their respective group allocation and the provers were unaware of the identity of the proving substance. The fresh venom sourced from a wild, Berg adder, was processed according to the German Homoeopathic Pharmacopoeia (Appendix G) to produce the 30CH Homoeopathic potency thereof. Six lactose powders were dispensed to each prover (either placebo or verum) and taken sublingually three times a day or until the onset of symptoms. Symptoms were recorded by the provers in journals over 4 weeks and were closely supervised by the researcher. When the symptoms subsided, the combined journals were collected, collated, analysed, interpreted and validated. Accepted symptoms were converted to materia medica and Repertory format. Results : The proving yielded a total of 903 rubrics, of which 18 were newly created. The systems mostly affected were Dreams, Mind, Head and Eye. Comparison of proving symptoms to that of venom toxicology, as seen in case studies of envenomation by Bitis atropos, yielded similar results, as the sensations experienced in provers closely matched that of known venom toxicology. On repertorisation of the proving symptoms, the existing remedies that were closely related were Sepia officinalis, Lachesis mutus and Argentum nitricum. Further repertorisation of toxicological symptoms indicated a further relation to Belladonna, Natrum muriaticum and Hyoscyamus niger. Conclusion : Clearly observable signs and symptoms were produced by healthy provers in response to administration of Bitis atropos 30CH, in addition there was a significant degree of similarity between proving symptoms and that of known toxicology of the crude substance. The researcher identified Sepia officinalis, Lachesis mutis and Argentum nitricum as the three most similar existing homoeopathic remedies and a detailed comparison thereof was conducted. A further repertorisation of the toxicological symptoms of envenomation by the snake, yielded the remedies Belladonna, Natrum muriaticum and Hyoscyamus niger which were also compared to Bitis atropos.

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2013. / Introduction The aim of this study was to investigate the homeopathic potential of Bitis atropos 30CH (Homoeopathically prepared Berg adder venom) and to compare the materia medica of Bitis atropos with that of existing remedies originating from remedies derived from the same genus: Bitis. It was hypothesised that the thirtieth centesimal potency of the substance Bitis atropos would produce clearly observable signs and symptoms in healthy volunteers, furthermore it was hypothesised that the materia medica of Bitis atropos would be comparable with those of existing remedies originating from the genus Bitis. Methodology The homeopathic drug proving of the substance Bitis atropos 30CH took the form of a double-blinded, randomised, placebo controlled trial. A total of 28 provers took part in the proving, twenty one percent (6 provers) were randomly administered placebo, the other seventy nine percent (22 provers) were randomly administered verum (active proving drug). Each prover received six lactose powder sachets, either placebo or verum, and were instructed to take one powder three times a day or until symptoms arose. Symptoms induced in healthy provers by Bitis atropos or placebo were recorded in journal format on a daily basis for a period of 4 weeks or until symptoms subsided. This data was subsequently transcribed into nomenclature suitable for the materia medica and repertory. A general picture of the remedy was described which according to the Law of Similars forms the clinical indications of the substance in homoeopathic practice. A concurrent study of the proving of Bitis atropos 30CH was conducted by Brijnath (2013), and focused on comparing the results of the proving with the venom toxicology of the snake and other related remedies. Results A wide variety of mental, emotional and physical symptoms were produced. Some of the main themes included feelings of antagonism with one’s self, polarity, anxiety, irritability and a lack of focus with a feeling of confusion. Some of the physical symptoms produced were a lack of energy, fatigue, temperature sensitivity, skin eruptions, eye symptoms, ear symptoms, back pain, asthma symptoms, and an increase in libido. The symptoms from the proving of Bitis atropos 30CH were subsequently compared with remedies that belong to the same genus: Bitis. This analysis aimed to demonstrate the similarities between the remedies in the same genus: Bitis. A significant degree of similarity was noted within the mental sphere, where the remedies shared the same themes of anxiety, irritability, polarity, confusion and lack of mental focus. Some of the physical symptoms shared by the remedies were those of respiratory symptoms, temperature sensitivity, fatigue, lack of energy and headaches and an increased libido. Conclusion This investigation supported the hypothesis that Bitis atropos 30CH would produce clear and observable signs and symptoms in healthy volunteers in addition it supported the hypotheses that the materia medica produced would be comparable to the existing remedies sharing the same genus i.e.- Bitis arietans arietans(Puff adder) and Bitis gabonica gabonica (Gaboon viper).

Na África subsaariana, as serpentes do gênero Bitis são de extrema importância, pois suas vítimas apresentam sintomas como dano local, hemorragia e uma severa hipotensão. Este trabalho identificou moléculas capazes de inibir a atividade da enzima conversora de angiotensina I (ECA) presentes no veneno de quatro serpentes do gênero Bitis. Para isto, as porções de baixa massa molecular desses 4 venenos foram fracionadas em RP-HPLC e as frações com boa inibição sobre a atividade da ECA foram analisadas por espectrometria de massas. Foram identificados 34 oligopeptídeos ricos em prolina (PRO), sendo 8 sintetizados e suas constantes de inibição (Ki) determinadas. Em testes com substratos naturais da ECA, angiotensina I e bradicinina, foi constatada a maior inibição da hidrólise da angiotensina I por quatro PROs. Todos os PROs in vivo reduziram a pressão arterial, e seis deles aumentaram a frequência cardíaca em ratos Wistar. Com isto, conclui-se que existem toxinas no veneno de serpentes do gênero Bitis responsáveis pela hipotensão. / In the sub-saharian Africa, snakes from the Bitis genus are of extreme medical importance, since its victims show symptoms as local tissue damage, hemorrhage and a severe hypotension. This work identified molecules that inhibit the angiotensin I converting enzyme (ACE) in the venom of 4 snakes from the Bitis genus. The low molecular portions of the venom of these snakes were fractionated in RP-HPLC and the fractions that efficiently inhibited the ACE activity were analyzed by mass spectrometry. 34 proline-rich oligopeptides were identified, 8 of them synthesized and had their inhibition constants (Ki) determined. In tests using natural substrates of ACE, angiotensin I and bradykinin, the angiotensin I hydrolysis were better inhibited by four PROs. In vivo tests results showed that all PROs decreased the mean arterial pressure and six of them increased the heart rate. Therefore, we can conclude that there are toxins present in the venom of Bitis capable of cause hypotension.

Na África subsaariana, as serpentes do gênero Bitis são de extrema importância, pois suas vítimas apresentam sintomas como dano local, hemorragia e uma severa hipotensão. Este trabalho identificou moléculas capazes de inibir a atividade da enzima conversora de angiotensina I (ECA) presentes no veneno de quatro serpentes do gênero Bitis. Para isto, as porções de baixa massa molecular desses 4 venenos foram fracionadas em RP-HPLC e as frações com boa inibição sobre a atividade da ECA foram analisadas por espectrometria de massas. Foram identificados 34 oligopeptídeos ricos em prolina (PRO), sendo 8 sintetizados e suas constantes de inibição (Ki) determinadas. Em testes com substratos naturais da ECA, angiotensina I e bradicinina, foi constatada a maior inibição da hidrólise da angiotensina I por quatro PROs. Todos os PROs in vivo reduziram a pressão arterial, e seis deles aumentaram a frequência cardíaca em ratos Wistar. Com isto, conclui-se que existem toxinas no veneno de serpentes do gênero Bitis responsáveis pela hipotensão. / In the sub-saharian Africa, snakes from the Bitis genus are of extreme medical importance, since its victims show symptoms as local tissue damage, hemorrhage and a severe hypotension. This work identified molecules that inhibit the angiotensin I converting enzyme (ACE) in the venom of 4 snakes from the Bitis genus. The low molecular portions of the venom of these snakes were fractionated in RP-HPLC and the fractions that efficiently inhibited the ACE activity were analyzed by mass spectrometry. 34 proline-rich oligopeptides were identified, 8 of them synthesized and had their inhibition constants (Ki) determined. In tests using natural substrates of ACE, angiotensin I and bradykinin, the angiotensin I hydrolysis were better inhibited by four PROs. In vivo tests results showed that all PROs decreased the mean arterial pressure and six of them increased the heart rate. Therefore, we can conclude that there are toxins present in the venom of Bitis capable of cause hypotension.