M.Tech. (Homoeopathy) / Baptisia tinctoria and Thuja occidentalis are reported to be immunostimulants, and thus have an effect on white blood cells. Little formal research has been done to demonstrate their effects on the different white cell populations. The purpose of this study was to determine the effects of these substances on the circulating leukocytes, and to compare these effects to a placebo. An initial full blood count was conducted to establish a baseline level for each subject. The subjects were required to take 18.75 millilitres of the medication or placebo in split doses over a three-hour period. Thereafter, a second full blood count was taken at one-hour intervals. The medication appeared to cause an increase in the lymphocyte count, thus suggesting a possible indication for viral infection. There was an increase in both groups of the total WBC count as well as in the lymphocyte count, raising the question of what substance actually caused these changes to occur. Expansion of this study, including using a larger sample size and longer test period, may be required to validate these results.

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The field of cancer therapeutic development has been dominated by two research and discovery paradigms, the cytotoxicity-based or phenotype driven strategy and the target-based rational approach. This thesis describes the standardization of novel assays used in both approaches and the discoveries made using these processes. Rational drug design or the target-based approach to discovering novel anti-cancer agents requires a basic understanding of the oncogenic signals that induce uncontrolled cellular proliferation. c-MET is a proto-oncogene, linked to a number of different cancers, that encodes a receptor tyrosine kinase. As an oncogene, c-MET has been shown to transform cells in the laboratory setting and is dysregulated in number of malignancies. Thus, we sought to discover a small molecule inhibitor of c-MET kinase activity by screening a novel library of small molecules. In the second part of this dissertation, we describe the standardization of a high-throughput assay to identify putative c-MET inhibitors and the results of our screening attempt. Cytotoxicity-based screening is another validated approach that is used to discover anti-cancer agents. As a parallel program to our c-MET discovery effort, we designed a high-throughput cytotoxicity assay to identify a novel small molecule with high cytotoxic activity towards tumor cells. The result of this screen was the identification of ON015640, a novel anti-cancer therapeutic with tubulin-depolymerizing activity. Throughout the course of this project, we tried to discern the advantages and disadvantages of the two predominant paradigms in cancer therapeutic research. Both strategies require careful assay design and an acute understanding of the molecular and genetic underpinnings of cancer. While it is clear that structure-based rational drug design has its merits and its success stories, it has become increasingly clear that seeking out a desired biological effect may serve as a more effective staring point when dealing with cancers for which no clear oncogene addiction phenotype has been observed. / Molecular and Cellular Physiology

Equines have been used for utilized for manual labor, recreation, and companionship amongst many other valuable conveniences since their domestication. As the modern horse progressed from livestock to athlete, attention was paid to the body conformation to be used as an indicator of biomechanics and can dictate equine performance. Poor conformation can put physical limitations on the body and predispose the horse to injury and chronic disease. When not managed properly, these flaws can lead to injury, lameness, and premature retirement in sport horses. The distal limb is composed of tendons and ligaments that are all susceptible to tear or rupture. Protective wraps or boots are typically applied to the distal limb prior to exercise to prevent superficial injury from the environment or interference. However, these preventatives can trap heat against the skin which can have detrimental effects on the fibroblasts which can lead to failure. It was not until the early twentieth century that the idea of equine physiotherapy was adopted, and practices changed to meet remedial needs and create a sustainable, healthy equine athlete. Equine physiotherapy is a broad-spectrum term used to describe the therapeutic efforts made to keep the body in good health by means of prevention of injury to improve or maintain performance. Traditionally, therapeutics are administered by a veterinarian or trained professional in the event of an existing injury. In recent years therapeutics have been commercialized and are readily available for everyday preventative use. The most common readily available treatments being variations of pulsating electromagnetic fields (PEMF), vibration therapy, cryotherapy, and thermotherapy. When used prior to or after exercise, the therapeutics are designed to prepare the body for exercise and improve recovery by increasing circulation and down regulating the inflammatory response. The studies performed evaluate the efficacy of Rambo®Ionic (Horseware, Dundalk,Ireland), Lux Ceramic Therapy® (Schneider Saddlery Co., Inc., Ohio, USA), and Ice-Vibe® (Horseware, Dundalk,Ireland) therapeutic boots when applied to the distal limb as per manufacturer recommendation. The first study evaluated the therapeutic boots ability to alter performance performing gait analysis using the ALOGO™ MovePro (Alogo Technologies, Switzerland) stride sensor, blood analysis measuring serum concentrations of C reactive protein (CRP), basic fibroblast growth factor (bFGF) and tenascin-C (TN-C), and capturing thermal images of the distal limb using an HT-19 thermal imaging camera (HTI, La Vergne, TN). In this study, eight healthy horses were exercised for approximately ten minutes per day for five consecutive days. There was a ten-day washout period where the horse received no treatment between each period; there was a total of four periods. The second study only evaluated Rambo®Ionic (Horseware, Dundalk,Ireland) and Ice-Vibe® (Horseware, Dundalk,Ireland) therapeutic boots on seventeen healthy horses in the Virginia Tech equitation lesson program. There were three periods with five days of consecutive data collection and a ten-day washout period in between where the horses received no treatment. Gait analysis was measured using the ALOGO™ MovePro (Alogo Technologies, Switzerland) stride sensor and a blind behavioral analysis was performed to analyze behavioral changes under saddle in response to a rider. / Master of Science / Equines have been used for utilized for manual labor, recreation, and companionship amongst many other valuable conveniences since their domestication. As the modern horse progressed from livestock to athlete, attention was paid to the structure of the horse, otherwise known as conformation. Conformation is an indicator of physical movement and can dictate what uses the horse is best suited for. In undesirable cases, poor conformation can put physical limitations on the body and predispose the horse to injury and chronic disease. When not managed properly, these flaws can lead to injury, lameness, and premature retirement in sport horses. The distal limb is a particularly vulnerable structure. It is free of muscle and is comprised of tendons, ligaments, and mobile joints. A protective wrap or boot is typically applied to the distal limb prior to exercise which can have detrimental effects on the cellular components of the associated structures which can lead to failure. It was not until the early twentieth century that the idea of equine physiotherapy was adopted, and practices changed to meet remedial needs and create a sustainable, healthy equine athlete. Equine physiotherapy is a broad-spectrum term used to describe the therapeutic efforts made to keep the body in good health by means of prevention of injury to improve or maintain performance. Traditionally, therapeutics are administered by a veterinarian or trained professional in the event of an existing injury. In recent years therapeutics have been commercialized and are readily available for everyday preventative use. The most common readily available treatments being variations of pulsating electromagnetic fields (PEMF), vibration therapy, cryotherapy, and thermotherapy. When used prior to or after exercise, the therapeutics are designed to prepare the body for exercise and improve recovery by increasing circulation and down regulating the inflammatory response. The studies performed evaluate the efficacy of Rambo®Ionic (Horseware, Dundalk,Ireland), Lux Ceramic Therapy® (Schneider Saddlery Co., Inc., Ohio, USA), and Ice-Vibe® (Horseware, Dundalk,Ireland) therapeutic boots when applied to the distal limb as per manufacturer recommendation. The first study evaluated the therapeutic boots ability to alter performance performing gait analysis using the ALOGO™ MovePro (Alogo Technologies, Switzerland) stride sensor, blood analysis measuring serum concentrations of C reactive protein (CRP), basic fibroblast growth factor (bFGF) and tenascin-C (TN-C), and capturing thermal images of the distal limb using an HT-19 thermal imaging camera (HTI, La Vergne, TN). In this study, eight healthy horses were exercised for approximately ten minutes per day for five consecutive days. There was a ten-day washout period where the horse received no treatment between each period; there was a total of four periods. The second study only evaluated Rambo®Ionic (Horseware, Dundalk,Ireland) and Ice-Vibe® (Horseware, Dundalk,Ireland) therapeutic boots on seventeen healthy horses in the Virginia Tech equitation lesson program. There were three periods with five days of consecutive data collection and a ten-day washout period in between where the horses received no treatment. Gait analysis was measured using the ALOGO™ MovePro (Alogo Technologies, Switzerland) stride sensor and a blind behavioral analysis was performed to analyze behavioral changes under saddle in response to a rider.

This study investigated the beneficial potential effects of grape pomaces obtained after winemaking of different Mediterranean grape varieties from crude materials to their in vivo effectiveness. Grapes and their respective grape pomaces from six different V. vinifera L. cultivar were studied namely Grenache (from two different locations [GRE1 and GRE2]), Syrah (from two different locations [SYR1 and SYR2]), Carignan (CAR), Mourvèdre (MOU), Counoise (COU) and Alicante (ALI) grape varieties from the Rhône Valley. The comparison of several wine industry by-products with their respective grapes provided evidence that pomace remaining at the end of the winemaking process can be very rich sources of antioxidants. The quantitative and qualitative distribution of polyphenols by HPLC-PDA-Fluo-MS in grape pomaces showed significant differences through varieties and vintages varying from 15% to 70% of polyphenols extracted. Seeds from Grenache (GRE1), Syrah (SYR1) and skins from Syrah (SYR1), Carignan and Alicante were of particular interest because of their higher polyphenol contents in terms of flavan-3-ols (monomers, dimers and trimers) up to 8.7 mg/g DW and anthocyanins (glycosides, acetylated and coumaroylated derivatives up to 17.40, 1.57 and 2.38 mg/g DW, respectively). The investigation of aqueous and hydro-alcoholic 70% extracts of seeds from Carignan and Syrah (SYR1) and skins from Carignan and Alicante was carried out as they contained high levels of total phenols and antioxidant activity. Several extracts, were tested in order to evaluate their in vivo biological effects on hypertension using a spontaneously hypertensive rat (SHR) model. A series of different grape pomace extracts were tested in association with verapamil. All in vivo experiments demonstrated that some grape pomace extracts administrated with or without co-ingestion with verapamil possessed an anti-hypertensive activity. This was evident with GRE1 (EA70) seed pomace extract, SYR1 (EA70) seed pomace extract, ALI (EA70) skin pomace extract administrated alone and with GRE1 (EA70) seed pomace extract, SYR1 (EAQ) seed pomace extract, ALI (EA70) skin pomace extract and SYR2 (EAQ) skin pomace extract administrated in association with verapamil. Grape pomace extracts with or without co-ingestion with verapamil were absorb as phase II metabolites mainly including glucuronide, O-methyl glucuronide, sulfate, and O-methyl sulfate derivatives of (epi)catechin which arise from the metabolism of monomeric flavan-3-ols. The detection by HPLC-PDA-Fluo-MSn and GC-MS of microbial-derived metabolites of flavan-3-ols, hydroxyphenyl-γ-valerolactones in their glucuronide and sulfate forms confirmed the absorption of metabolites derived from both monomeric and polymeric flavan-3-ols from grape pomace extracts and subsequent post-absorption conjugation. Numerous metabolites derived from further microbial degradation of hydroxyvalerolactones were also detected. The urinary excretion of these metabolites accounted for a larger proportion of the total polyphenol ingested than phase II metabolites of monomeric flavan-3-ols, indicating the important role of intestinal bacteria in the metabolism of polymerized procyanidins. All these metabolites may have exerted biological effects during the period in which they circulated in the bloodstream. This study constitutes the first step of assessing grape pomace as an enhancer of the verapamil, an anti-hypertensive drug. Substantial levels of polyphenols, especially flavan-3-ols, procyanidins and anthocyanins, remain in pomace after the winemaking process in quantities sufficient to exert anti-hypertensive effects. In addition, according to the extract used and its composition, it is feasible to modulate anti-hypertensive effects by amplifying or decreasing polyphenols and/or verapamil absorption.

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2013. / The proving study of Strychnos henningsii 30CH was primarily conducted to extract as many symptoms as possible from healthy provers to create a Homoeopathic picture of the drug. This would allow practitioners in clinical practise to prescribe Strychnos henningsii 30CH based on the Law of Similars. The second part of this study was to assess the symptoms produced, and thereafter determine the relationship to the natural history of the Strychnos henningsii plant as it relates to the Doctrine of Signatures. Methodology The Homoeopathic drug proving of Strychnos henningsii 30CH took the form of a mixed-method triple-blind, placebo-controlled study. The proving population consisted of a minimum of 32 subjects who met all the inclusion criteria. The proving was conducted by 4 M.Tech.Hom students, under the supervision of the principal researcher. The 32 provers were randomly divided into four equal groups of eight provers, with each group supervised by one of four M.Tech.Hom student researchers. Nine powders each of the respective test substance (verum or placebo) was randomly assigned by an independent clinician to 32 prover numbers (16 verum and 16 placebo). Randomisation was conducted by an independent clinician who was unaware of the proving substance. The physical and behavioural symptoms that were noted by the provers were extracted from their prover journals, case-histories and post-proving group discussions. This was then written up into Materia Medica and Repertory format and graded accordingly. Once this proving data was captured it allowed for the application of the Doctrine of Signatures. During this analysis, similarities were compared between the behaviour of the patient and the behaviour of the substance in nature, which indicated the therapeutic action of the plant. The main characteristics used to link the Strychnos henningsii plant in its natural state to the Homoeopathic remedy developed was the plants habitat, kingdom, toxicity, structure, Anthroposophy and Vibrational therapy. By applying the Anthroposophical and vibrational therapy view, it allowed the researcher to establish a more holistic approach. Results A broad spectrum of symptoms was obtained which resulted in the formation of 876 rubrics. The areas that Strychnos henningsii had a profound affinity for were the mind which yielded 170 rubrics, head (76 rubrics), extremities (82 rubrics), dreams (91 rubrics) and the generals (80 rubrics). These rubrics were used in the evaluation of the Doctrine of Signatures. The sensation of heat, dryness and burning appeared to be an integral part of the manifestation of symptoms in this proving study which correlated to the habitat of the plant in its natural environment. Many mind themes were noted, but in particular emotional sensitivity was one of the major themes. Sensitivity is the Plant Kingdom’s key sensation in general. The remedy was prepared using the bark of the plant which contained high levels of the alkaloid strychnine. This reflected in the provers symptoms (itching, skin eruptions, cramps, stiffness, tingling). The structure, colour, mode and speed of growth were all factors which yielded satisfactory comparative results. Chakras, Colour Therapy and Anthroposophy allowed the researcher to apply a more dynamic scientific methodology. This tied in well with the Doctrine of Signatures and essentially provided a broader understanding of the remedy. Conclusion The hypotheses of this study were largely validated by the symptoms produced and analysis conducted, after applying the scientific methodology. The Doctrine of Signatures evaluation helped to reveal the intrinsic nature of Strychnos henningsii, further highlighting the underlying themes in the remedy and explained certain symptoms in more detail and finally distinguished between the behaviour of the patient and the substance in nature aiding us with a better understanding for clinical practise. It is important to note that recommendations have been made for future provings.

Thesis (M.Tech.: Chiropractic) -Dept. of Chiropractic, Durban Institute of Technology, 2002 xiii, 93 leaves / The purpose of this study was to determine the short to medium term effectiveness of Proprioceptive Neuromuscular Facilitaion (P.N.F.) stretching [using the Contract- Relax-Antagonist-Contract (C.R.A.C.) technique] as an adjunct treatment to cervical manipulation in the treatment of Mechanical Neck Pain.