Dissertations / Theses on the topic 'Extremities (anatomy)'

Skeletal muscles of the limb are derived from somites and their precursors migrate to the limb prior to muscle formation. Upon migration, a limited number of stem cells multiply and differentiate to give rise to fusion-competent muscle cells, which fuse to form the multinucleated myotubes. During the course of myogenesis there is thus a period of few days when cells at different developmental stages such as migrating, proliferating, differentiating and fully differentiated co-reside within the developing limb bud. Current understanding on how these cells interact and behave during early and later myogenesis in vivo is lacking. The aim of this project was to identify and further classify the mononucleated myogenic cells present within the developing limb muscle and examine their behaviours at different stages of myogenesis. The lack of an appropriate method to extract and visualise cellular constituents of developing muscles has been a major limitation hindering such investigations in vivo. In this project, we first developed a unique cell isolation method to extract mononucleated cells from developing muscles, allowing examination of mononucleated cells in vivo using immunocytochemistry. As Pax3, Pax7 and Myogenic Regulatory Factors (MRFs) are the key players for the muscle formation, they were used to mark the different myogenic sub-populations. The results from chicken and rats clearly demonstrate that three myogenic cell pools, namely Pax3, Pax7 and MRFs positive cells, and 4 sub-populations formed by their overlap, co-exist in specific proportions within the developing limb muscle, and that their proportions undergo dynamic changes during the course of myogenesis. The most striking observation was that the sizes of Pax3 and MRF compartments remain constant while that of Pax7 compartment increases dramatically during myogenesis. Thus each myogenic cell compartment in the developing muscle has different cell kinetics during primary and secondary myogenesis. The dynamic changes in the proportions of these myogenic sub-populations may constitute a dynamically maintained cellular niche, within which the muscle stem cells reside. Our study suggests that the concept of community effect - the interaction between a group of cells and their surrounding cells, originally from invertebrate muscle system, may be conserved in mammalian systems. Furthermore, this study for the first time, reports that the earliest fully differentiate muscle cells in the rat hindlimb are highly elongated mononucleated cells which express Pax3, MyoD, myogenin and myosin but not Myf-5 protein. In summary, this study provides quantitative data to demonstrate dynamic changes in various mononucleated myogenic cell populations during skeletal muscle formation and reveals that Pax7(+ve) population becomes significantly upregulated during secondary myogenesis.

Thesis (Ph. D.)--West Virginia University, 2008.
Title from document title page. Document formatted into pages; contains xv, 239 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

It has been shown that maximal, bilateral efforts result in both a force and EMG deficit when compared to maximal, unilateral activation of the same musculature. It is unclear whether this deficit is the result of interactions of central or peripheral origin. The first aim study investigated the bilateral performance index (BPI (%) = [100 x bilateral force/(right unilateral + left unilateral forces)] - 100) for maximal, isometric, extensor torques about the knee joint in three groups of subjects: untrained (never lifted weights), cyclists (leg musculature trained reciprocally), and weightlifters (legs trained bilaterally). The BPI for the weightlifters (+7.0 ± 5.0%) was significantly (p < 0.05) greater than the BPI of the cyclists (-4.0 ± 6.3%) or the untrained subjects (-9.7 ± 5.2%). These results indicate that the inhibitory mechanisms previously proposed to act during bilateral efforts are inadequate, and that excitatory factors must be present to achieve a BPI > 0. The second aim study showed that the BPI can be altered as a result of three weeks of bilateral isometric strength training. The BPI's for the control and unilateral training groups were not significantly different pre- to posttraining. However, the BPI of the bilateral training group increased significantly (p < 0.05) from -3.7 ± 6.9% prior to training, to +4.2 ± 4.4% after training. These findings indicate that bilateral strength training can alter the relationship between unilateral and bilateral force output. The third aim study demonstrated that subjects with a positive BPI (+6.8 ± 4.3%) responded differently to an afferent perturbation (electrical stimulation) than subjects with a negative BPI (-10.0 ± 5.2%). The negative BPI group showed a 5.7 ± 3.4% facilitation in force during contralateral electrical stimulation. This was significantly (p < 0.05) less than the 16.5 ± 7.5% facilitation shown by the positive BPI group. These results indicate that afferent feedback can alter the force output in the contralateral limb, and may thereby play a role in unilateral-bilateral force differences.

Slits and their Roundabout (Robo) receptors were identified based on their role in regulating axon guidance, but are known to play multiple roles in development, including regulating heart development and myoblast migration. There are 3 vertebrate Slits (Slit1 – 3) and 4 Robos (Robo1 – 4), and previous work has demonstrated expression of Slit and Robo family members in and around developing joints where their function is unclear. Mutations in human Robo3 have been linked to degenerative joint disorders, such as scoliosis and rheumatoid arthritis. Misregulation of other members of the Slit/Robo signalling pathway is also reported in cells from arthritic joints. This suggests that Slit/Robo signalling is required for normal joint development and/or maintenance, though our understanding of their roles in these processes is rudimentary. The central question of my thesis is to determine the role/s of Slit/Robo signalling in limb and joint development. In situ hybridisation confirmed strong expression of Slits and Robos throughout mouse limb and joint development, though no expression of Slit1 or Robo3 was detected. Analysis of Slit1/2, Slit3 and Robo1 mutant (loss-of-function) mice revealed normal limb development, however misexpression of dominant-negative Robo2 during chicken limb development caused shortening of cartilage elements. To begin to identify molecular changes that may compensate for the loss of Slit/Robo signalling I demonstrated members of the Sema3/PlexinA/Nrp axon guidance family are expressed in patterns comparable to those of Robo1, Robo2 and Slit3. I discovered that PlexinA1 is downregulated in Slit3 mutant mouse limbs. My results suggest the role for Silt/Robo signalling may be more complex than previously thought and do not define a clear role for signalling during limb development. My results suggest the role for Silt/Robo signalling may be more complex than previously thought and do not define a clear role for signalling during limb development. Previous work has linked Slit/Robo signalling to development of degenerative joint disorders, and I propose some hypotheses as to how Slit/Robo signalling could cause bone and joint defects.

Thesis (Ph.D.)--University of Missouri-Columbia, 2007.
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 19, 2009) Vita. Includes bibliographical references.

Correct race and sex determination of unknown skeletal material is an important aspect of forensic anthropology. Numerous studies have focused on the differences, both osteometric and morphological, between the sexes of a particular racial phenotype, between race groups, and populations. From previous work by a variety of researchers, the necessity of population specific standards for identification has been demonstrated. The purpose of this research was to examine the metric and morphological differences in the pelvis between the sexes and races of South African whites and blacks. Results will be used in developing standards of identification tailored to this population. A sample of 400 known sex/race os coxae were examined. Skeletal material was obtained from the Pretoria collection housed at the University of Pretoria, Department of Anatomy and the Dart collection located at the University of Witwatersrand, Department of Anatomical Sciences. A series of thirteen measurements and five morphological characteristics were examined. Indices were calculated from data obtained from the metric analysis. Left and right sides were examined and those bones visibly pathologically deformed were excluded from the study. Data were subjected to SPSS stepwise and direct discriminant analysis. Results showed ischial length as the most sexually dimorphic characteristic in whites, while acetabulum diameter was best in blacks. Four functions (using pelvic dimensions) were developed for determining sex. Highest accuracies were achieved from function 1 (including all dimensions) which correctly classified 92-96% of individuals. Race differences were also investigated. Pubic length was chosen as best for discriminating between races for males and iliac breadth as best in females. Accuracies were 86-89% for males and 82-88% for females. Accuracies for sex discrimination were consistent with earlier studies. Morphological results yielded >80% accuracy for all traits in white males except greater sciatic notch shape where only 33% were correctly classified. A population specific variation in sciatic notch shape was observed where >50% of the white males had a wide sciatic notch previously thought to be a female expression. Black males recorded 81 % correct classification for pubic shape and >90% for the remaining characteristics. Greater sciatic notch and pubic bone shape achieved highest accuracies with 96% for both traits in white females, and 84% and 88% in black females respectively. In conclusion, this study conclusively demonstrates that race and population differences affect the expression of sexual dimorphism and must be accounted for to develop the most effective methods of analysis.
Dissertation (MSc)--University of Pretoria, 2001.
Anatomy
unrestricted

As Doenças Osteomusculares Relacionadas ao Trabalho (DORT) são as patologias que demandam atenção das empresas do setor industrial devido à alta incidência de absenteísmo e pela prevalência nos afastamentos previdenciários, sendo os membros superiores o segmento corporal mais atingido. A mensuração da força muscular através da dinamometria é um dos métodos para estimar a capacidade funcional de um indivíduo, porém as tabelas internacionais de valores dinamométricos que são utilizadas como parâmetros de normalidade são conflitantes com a população do setor industrial brasileiro. Neste contexto, percebe-se a necessidade de criar um padrão de normatização específico para o setor da indústria eletromecânica que auxilie a medicina ocupacional na percepção de aptidão para execução de uma atividade laboral, prevenindo o aparecimento de DORT. O objetivo deste estudo é desenvolver valores de normalidade nos exames de dinamometria palmar e escapular através do método de cartas percentílicas, que atendessem a população brasileira do setor industrial, correlacionando com as variáveis: faixa etária, sexo e lado de dominância, para servir de apoio na decisão de aptidão profissional. Para tanto, foi realizado um estudo retrospectivo, descritivo e transversal com 2902 funcionários saudáveis entre 16 e 63 anos, a partir de banco de dados de empresas do setor eletromecânico da região metropolitana de Curitiba. Os dados foram analisados a partir da estatística descritiva com medidas de posição e dispersão e cartas de referência foram elaboradas a partir do método LMS (Least Median Square), sendo L transformação “BoxCox”, M mediana e S coeficiente de variação. Os resultados mostraram que as medianas de dinamometrias palmares desta pesquisa estão abaixo dos estudos internacionais e que as curvas percentílicas formadas pelos valores das dinamometrias desta amostragem apresentam um valor progressivo com a idade. Para o gênero masculino, a metodologia permitiu a formatação de gráficos de que apontam intervalos normalidade de acordo com cada idade. Conclui-se assim, que os valores dinamométricos palmares e escapulares encontrados hoje na literatura internacional não se aplicam para a população do setor eletromecânico nacional. O método de cartas percentílicas relacionadas com a idade e gênero permitiu formatar uma modelagem matemática com gráficos de normalidade, de fácil empregabilidade, que quando relacionado ao grau de risco ergonômico do posto de trabalho auxilia o raciocínio médico quanto a aptidão para assumir uma determinada atividade laboral. Como proposta futura, sugere-se a continuidade de estudos com esta mesma metodologia para o gênero feminino e a associação de outros métodos tecnológicos sensíveis à detecção e prevenção de doenças osteoarticulares relacionadas ou não, com o trabalho, como a termografia
The Musculoskeletal Diseases related to work (WRMD) are the pathologies that require attention of companies in the industrial sector due to high incidence of absenteeism and the prevalence in through INSS, and the upper limbs the most affected body part. The measurement of muscular strength by grip strength is one of the methods to measure the functional capacity a person, but international tables dynamometric values that are used as normal parameters are conflicting with the population of the Brazilian industrial sector. In this context, we see the need to create a specific standards model for the electromechanical industry sector to assist occupational medicine to check the capability to execute a labor activity, preventing from DORT. The aim of this study is to develop normal values for palmar grip strength and scapular tests by percentile cards method that met the Brazilian population in the industrial sector, correlating to the variables: age, gender and hand dominance, to provide support in the fitness professional decision. A retrospective, descriptive cross-sectional study was made with 2902 healthy employees between 16 and 63 years from database of electromechanical companies of the Curitiba metropolitan area. The data was analyzed using descriptive statistics with position and dispersion measurements and reference cards have been elaborated from the LMS method (Least Median Square), where L is transformation "BoxCox", M is median and S is coefficient of variation. The results showed that the median grip dinamometric of this research are below international studies and that percentílicas curves formed by the values of dinamometrias this sample have a progressive value with age. This methodology for the male gender allowed the formatting charts that show normal ranges according to each age. It was concluded that the dynamometric values grip and scapular found today in the international literature are contradictory when applied to the population of the national electromechanical industry. Percentile cards method related to age and gender, it was possible to format a mathematical modeling with normal graphics, easy usage, when related to the degree of ergonomic risk of working location aids medical thinking as the ability to take a certain labor activity. As a future proposal, it is suggested to continue their studies with the same methodology for the female gender and the association of other technological methods sensitive to the detection and prevention of osteoarticular diseases related or not with work, as thermography.

Description d'un nouveau genre et d'une nouvelle espece d'iguanodontide en provenance du gisement de gadoufaoua. L'etude osteologique et biometrique, l'analyse et la reconstitution de la musculature pelvienne indiquent qu'il s'agit du premier ornithopode quadrupede franc actuellement connu. On precise sa phylogenie. On le compare avec les autres ornithopodes. L'interpretation des rapports biometriques concernant le squelette appendiculaire, bien que delicate, permet de differencier certains groupes. On analyse la position systematique du nouveau taxon ce qui nous amene a declarer lesothosaurus comme etant l'ornithopode s. S. Le plus primitif actuellement connu

Thesis (M.Tech.: Chiropractic)-Dept. of Chiropractic, Durban University of Technology, 2007 xiii, 77, Annexures 1-19, 19 leaves
The increasing contribution of chiropractors in health care has generated greater interest in understanding the characteristics of chiropractic practice patterns and treatments (Mootz et al., 2005). However, despite the rapid growth and extensive use of chiropractic, good descriptive data on chiropractors and their patients remains limited (Coulter and Shekelle, 2005). Even fewer studies have been reported which deal specifically with patients attending chiropractic-teaching clinics (Nyiendo and Olsen, 1988). According to Nyiendo and Haldeman (1986), there remains a paucity of empirical data regarding the type of patients seeking care at a chiropractic-teaching clinic and the types of treatments provided at these clinics. According to Till and Till (2000), South Africa is largely a developing country with scattered developed communities. Its requirements and opportunities as they relate to chiropractic may differ significantly from those in other developed countries. It was also estimated that in South Africa only a fraction of the country’s population have any notion of what chiropractic is, thus the largest challenge lies with educating the public about chiropractic (http://www.chiroweb.com, 2005). The lack of attention given to the chiropractic management of extremity conditions has contributed to a perception that chiropractic is unable to manage extremity conditions proficiently (Hoskins et al., 2006). There is a noted lack of research on the management of extremity conditions within chiropractic (Hoskins et al., 2006); therefore the current study focused on all components of the extremity system. Objectives: The purpose of this research is to conduct a descriptive study of extremity cases on record at the Durban University of Technology Chiropractic Day Clinic from 1995 to 2005 and the objectives are as follows: •To determine the prevalence of extremity complaints over the past decade at the Durban University of Technology Chiropractic Day Clinic. •To identify the demographics of patients that visited the Durban University of Technology Chiropractic Day Clinic. •To identify the most common presenting region and complaints of the extremity system as well as the aetiology and associated signs and symptoms of these complaints at the Durban University of Technology Chiropractic Day Clinic. •To identify the nature of the interventions and methods most commonly used in the management of patients at the initial consult and where possible contra-indications to any treatment modality

Indiana University-Purdue University Indianapolis (IUPUI)
Biological systems behave differently under different conditions. Advances in sequencing technology over the last decade have led to the generation of enormous amounts of condition-specific data. However, these measurements often fail to identify low abundance genes/proteins that can be biologically crucial. In this work, a novel text-mining system was first developed to extract condition-specific proteins from the biomedical literature. The literature-derived data was then combined with proteomics data to construct condition-specific protein interaction networks. Further, an innovative condition-specific differential analysis approach was designed to identify key differences, in the form of subnetworks, between any two given biological systems. The framework developed here was implemented to understand the differences between limb regeneration-competent Ambystoma mexicanum and –deficient Xenopus laevis. This study provides an exhaustive systems level analysis to compare regeneration competent and deficient subnetworks to show how different molecular entities inter-connect with each other and are rewired during the formation of an accumulation blastema in regenerating axolotl limbs. This study also demonstrates the importance of literature-derived knowledge, specific to limb regeneration, to augment the systems biology analysis. Our findings show that although the proteins might be common between the two given biological conditions, they can have a high dissimilarity based on their biological and topological properties in the subnetwork. The knowledge gained from the distinguishing features of limb regeneration in amphibians can be used in future to chemically induce regeneration in mammalian systems. The approach developed in this dissertation is scalable and adaptable to understand differential subnetworks between any two biological systems. This methodology will not only facilitate the understanding of biological processes and molecular functions which govern a given system but also provide novel intuitions about the pathophysiology of diseases/conditions.

Wong, Wan Man.
Thesis submitted in: December 2006.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2007.
Includes bibliographical references (leaves 85-98).
Abstracts in English and Chinese.
Abstract --- p.i
Abstract in Chinese --- p.iii
Acknowledgements --- p.v
Lists of Figures and Tables --- p.vi
Table of Abbreviations --- p.xi
Table of Contents --- p.xv
Chapter Chapter I --- Introduction
Chapter 1.1 --- Brain and Reproductive Organ Expressed Gene --- p.1
Chapter 1.2 --- Programmed cell death --- p.4
Chapter 1.3 --- Limb development in mouse --- p.8
Chapter 1.4 --- Role of BRE in apoptosis --- p.12
Chapter 1.5 --- Role of programmed cell death in interdigital tissue regression --- p.14
Chapter 1.6 --- Aim of study --- p.17
Chapter Chpater II --- Materials and methods
Chapter 2.1 --- Mice --- p.18
Chapter 2.2 --- In-situ hybridization
Chapter 2.2.1 --- Histology --- p.18
Chapter 2.2.2 --- Preparation of riboprobe for in-situ hybridization --- p.19
Chapter 2.2.3 --- In-situ hybridization --- p.20
Chapter 2.3 --- Interdigital tissue culture --- p.21
Chapter 2.4 --- Gene interference
Chapter 2.4.1 --- Construction of Bre-siRNA --- p.22
Chapter 2.4.2 --- siRNA transfection of cultured interdigital cells --- p.23
Chapter 2.5 --- Semi-quantitative RT-PCR
Chapter 2.5.1 --- Sample collection of interdigital cells and explants --- p.23
Chapter 2.5.2 --- RNA isolation and extraction --- p.24
Chapter 2.5.3 --- Reverse-transcription and cDNA synthesis --- p.25
Chapter 2.5.4 --- Polymerase chain reaction --- p.26
Chapter 2.6 --- Assay of cell viability by MTT --- p.28
Chapter 2.7 --- Comparative proteomics --- p.30
Chapter 2.7.1 --- Collection of interdigital cells --- p.30
Chapter 2.7.2 --- Preparation of cell lysate --- p.31
Chapter 2.7.3 --- Assay of protein concentration in cell lysate --- p.31
Chapter 2.7.4 --- Two-dimensional gel electrophoresis --- p.33
Chapter 2.7.5 --- Protein identification by mass fingerprinting --- p.36
Chapter 2.8 --- Statistical Method --- p.38
Chapter Chapter III --- Results
Chapter 3.1 --- Spatial and temporal expression of Bre in murine embryonic hindlimbs --- p.39
Chapter 3.2 --- Expression of Bre isoforms in interdigital tissues --- p.45
Chapter 3.3 --- Silencing of Bre expression by siRNA in interdigital cells --- p.49
Chapter 3.4 --- Effect on viability of Bre-silenced interdigital cells by siRNA --- p.51
Chapter 3.5 --- Comparative proteomic profile of Bre-silenced interdigital cultured cells --- p.53
Chapter 3.6 --- Identification of proteins that were differentially expressed by MALDI- TOF --- p.71
Chapter 3.7 --- The mRNA levels of proteins identified that were differentially expressed --- p.74
Chapter Chapter IV --- Discussion --- p.77
References --- p.85
Appendices --- p.99
Publication --- p.108

Cheung Ho Yan.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2005.
Includes bibliographical references (leaves 164-175).
Abstracts in English and Chinese.
Abstract --- p.i
Acknowledgements --- p.vi
Publications based on the work in this thesis --- p.vii
Table of content --- p.viii
Abbreviations --- p.xii
Chapter CHAPTER 1 --- INTRODUCTION --- p.1
Chapter 1.1 --- Traditional Chinese Medicine --- p.1
Chapter 1.1.1 --- Danshen --- p.2
Chapter 1.1.2 --- Chemical constituents --- p.5
Chapter 1.1.3 --- Pharmacological effects --- p.7
Chapter 1.1.3.1 --- On blood vessels --- p.7
Chapter 1.1.3.2 --- On blood pressure --- p.8
Chapter 1.1.3.3 --- On heart --- p.8
Chapter 1.1.3.4 --- On myocardial ischaemia and reperfusion --- p.9
Chapter 1.1.3.5 --- On platelet activity --- p.10
Chapter 1.1.3.6 --- Other actions --- p.11
Chapter 1.1.4 --- Clinical studies --- p.12
Chapter 1.2 --- The Vascular System --- p.13
Chapter 1.2.1 --- The circulation network --- p.13
Chapter 1.2.2 --- Physiology of blood vessels --- p.13
Chapter 1.2.3 --- Control of vascular lone --- p.14
Chapter 1.3 --- Mechanisms of Vasodilatation --- p.16
Chapter 1.3.1 --- Endothelium derived relaxant factors (EDRFs) --- p.16
Chapter 1.3.1.1 --- Nitric oxide (NO) --- p.16
Chapter 1.3.1.2 --- Prostacyclin (PGI：) --- p.17
Chapter 1.3.1.3 --- Endotheliun-derived hyperpolarization factors (EDHFs) --- p.18
Chapter 1.3.1.3.1 --- Epoxyeicosatrienoic acids (EETs) --- p.19
Chapter 1.3.1.3.2 --- Potassium ion (IC) --- p.20
Chapter 1.3.1.3.3 --- Gap junction --- p.20
Chapter 1.3.2 --- Signal transduction pathways --- p.21
Chapter 1.3.2.1 --- Guanylyl cyclase-cGMP pathway --- p.21
Chapter 1.3.2.2 --- Adenylyl cyclase-cAMP pathway --- p.22
Chapter 1.3.3 --- Ion channels in vascular smooth muscle cell --- p.24
Chapter 1.3.3.1 --- Potassium channels (K+ channels) --- p.24
Chapter 1.3.3.2 --- Calcium channels (Ca2+ channels) --- p.24
Chapter 1.3.3.3 --- Chloride channel (Cl channel) --- p.25
Chapter 1.3.4 --- Receptor-operated mechanisms --- p.27
Chapter 1.3.4.1 --- Muscarinic receptors --- p.27
Chapter 1.3.4.2 --- Adrenoceptors --- p.27
Chapter 1.3.4.3 --- Histamine receptors --- p.28
Chapter 1.3.4.4 --- CGRP receptors --- p.29
Chapter 1.3.4.5 --- Tachykinin receptors --- p.30
Chapter 1.4 --- Aims of the studies --- p.31
Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.32
Chapter 2.1 --- Extraction of Water and Lipid-solubie Fractions from Danshen --- p.32
Chapter 2.1.1 --- Preparation of water-soluble and lipid-soluble fractions --- p.33
Chapter 2.2 --- Experiments on Rat Knee Joint --- p.35
Chapter 2.2.1 --- Animals --- p.35
Chapter 2.2.2 --- Materials --- p.35
Chapter 2.2.3 --- Preparatory protocols --- p.37
Chapter 2.2.3.1 --- Anaesthesia of animals --- p.37
Chapter 2.2.3.2 --- Cannulation of trachea --- p.37
Chapter 2.2.3.3 --- Cannulation of carotid artery --- p.38
Chapter 2.2.3.4 --- Blood pressure measurement --- p.38
Chapter 2.2.4 --- Measurement of knee joint blood flow --- p.39
Chapter 2.2.4.1 --- Preparation for measurement of knee joint blood flow --- p.41
Chapter 2.2.5 --- Experimental protocols --- p.41
Chapter 2.2.5.1 --- Danshen on knee joint blood flow --- p.41
Chapter 2.2.5.2 --- Antagonists on Danshen --- p.41
Chapter 2.2.5.3 --- Positive controls --- p.43
Chapter 2.2.6 --- Image analysis --- p.44
Chapter 2.2.7 --- Data analysis --- p.44
Chapter 2.3 --- Experiments on Rat Femoral Artery --- p.45
Chapter 2.3.1 --- Animals --- p.45
Chapter 2.3.2 --- Materials --- p.45
Chapter 2.3.2.1 --- Chemicals --- p.45
Chapter 2.3.2.2 --- Physiological salt solution --- p.48
Chapter 2.3.3 --- Preparatory protocols --- p.48
Chapter 2.3.3.1 --- Small vessel myograph --- p.48
Chapter 2.3.3.2 --- Isolation and mounting of tissue --- p.49
Chapter 2.3.4 --- Experimental protocols --- p.50
Chapter 2.3.4.1 --- Studies on the vasodilator response to Danshen --- p.50
Chapter 2.3.4.2 --- Studies of antagonists on Danshen --- p.50
Chapter 2.3.4.2.1 --- Endothelium-dependent mechanisms --- p.51
Chapter 2.3.4.2.2 --- Endothelium-independent mechanisms --- p.54
Chapter 2.3.4.2.3 --- K+ channel blockers --- p.54
Chapter 2.3.4.2.4 --- Positive controls --- p.55
Chapter 2.3.4.3 --- Danshen on Ca2+-induced contraction --- p.56
Chapter 2.3.5 --- Data analysis --- p.57
Chapter CHAPTER 3 --- RESULTS --- p.58
Chapter 3.1 --- Danshen on Rat Knee Joint Blood Flow --- p.58
Chapter 3.1.1 --- Topical administration of Danshen --- p.58
Chapter 3.1.2 --- Antagonists on Danshen --- p.59
Chapter 3.1.2.1 --- Muscarinic receptor antagonist --- p.59
Chapter 3.1.2.2 --- β-adrenoceptor antagonist --- p.60
Chapter 3.1.2.3 --- Histamine receptor antagonists --- p.60
Chapter 3.1.2.4 --- Nitric oxide synthase inhibitor --- p.61
Chapter 3.1.2.5 --- Cyclo-oxygenase inhibitors --- p.62
Chapter 3.1.2.6 --- CGRPi receptor antagonist --- p.62
Chapter 3.1.2.7 --- NK1 receptor antagonist --- p.63
Chapter 3.1.2.8 --- Potassium channel inhibitor --- p.64
Chapter 3.1.2.9 --- "Combination of cyclo-oxygenase inhibitor, nitric oxide synthase inhibitor and CGRP1 receptor antagonist" --- p.64
Chapter 3.1.3 --- Antagonists on water-soluble fraction of Danshen --- p.91
Chapter 3.1.3.1 --- Nitric oxide synthase inhibitor --- p.91
Chapter 3.1.3.2 --- Cyclo-oxygenase inhibitors --- p.91
Chapter 3.1.3.3 --- CGRP1 receptor antagonist --- p.92
Chapter 3.1.3.4 --- NK1 receptor antagonist --- p.92
Chapter 3.1.3.5 --- Potassium channel inhibitor --- p.92
Chapter 3.2 --- Danshen on Rat Femoral Artery --- p.99
Chapter 3.2.1 --- Danshen on precontracted arterial ring --- p.99
Chapter 3.2.2 --- Endothelium-dependent mechanisms --- p.106
Chapter 3.2.3 --- Endothelium-independent mechanisms --- p.114
Chapter 3.2.4 --- K+ channel blockers --- p.119
Chapter 3.2.4.1 --- Effect on Danshen --- p.119
Chapter 3.2.4.2 --- Effect on water-soluble and lipid-soluble fractions of Danshen --- p.121
Chapter 3.2.4.3 --- Effect on Danshensu --- p.122
Chapter 3.2.5 --- Danshen on Ca2+-induced contractions --- p.133
Chapter CHAPTER 4 --- DISCUSSION --- p.138
Chapter 4.1 --- In Vivo Studies of Danshen on Rat Knee Joint Blood Flow --- p.139
Chapter 4.2 --- In Vitro Studies of Danshen on Isolated Rat Femoral Artery --- p.148
Chapter 4.2.1 --- Comparisons of the use of different precontractors --- p.148
Chapter 4.2.2 --- Investigations on endothelium-dependent mechanisms --- p.151
Chapter 4.2.3 --- Investigations on endothelium-independent mechanisms --- p.152
Chapter 4.2.4 --- Effects of K+ channel blockers --- p.154
Chapter 4.2.5 --- Inhibition of Ca2+ influx in vascular smooth muscle --- p.157
Chapter 4.3 --- Comparisons of Results from In Vivo and In Vitro Studies --- p.159
Chapter 4.4 --- Future Studies --- p.161
Chapter 4.5 --- Conclusion --- p.162
REFERENCES --- p.164

Indiana University-Purdue University Indianapolis (IUPUI)
Peripheral arterial disease is caused by plaque buildup in the peripheral arteries. Standard treatments are available when the blockage is proximal and focal, however when distal and diffuse the same type of the treatment options are not beneficial due to the diseased locations. Restoration of blood flow and further salvaging of the limb in these patients can occur in a retrograde manner through the venous system, called retroperfusion or arteriovenous reversal. Retroperfusion has been explored over the last century, where early side to side artery to venous connections had issues with valve competency prohibiting distal flows, edema buildup, and heart failure. However, more recent clinical studies create a bypass to a foot vein to ensure distal flows, and though the results have been promising, it requires a lengthy invasive procedure. It is our belief that the concerns of both retroperfusion approaches can be overcome in a minimally invasive/catheter based approach in which the catheter is engineered to a specific resistance that avoids edema and the perfusion location allows for valves to be passable and flow to reach distally. In this approach, the pressure flow relations were characterized in the retroperfused venous system in ex-vivo canine legs to locate the optimal perfusion location followed by in-vivo validation of canines. Six canines were acutely injured for 1-3 hours by surgical ligation of the terminal aorta and both external iliac arteries. Retroperfusion was successfully performed on five of the dogs at the venous popliteal bifurcation for approximately one hour, where flow rates at peak pressures reached near half of forward flow (37±3 vs. 84±27ml/min) and from which the slope of the P/F curves displayed a retro venous vasculature resistance that was used to calculate the optimal catheter resistance. To assess differences in regional perfusion, microspheres were passed during retroperfusion and compared to baseline microspheres passed arterially prior to occlusion in which the ratio of retroperfusion and forward perfusion levels were near the ratio of reversed and forward venous flow (0.44) throughout the limb. Decreases in critical metabolites during injury trended towards normal levels post-retroperfusion. By identifying the popliteal bifurication as a perfusion site to restore blood flow in the entirety of the distal ischemic limb, showing reversal of injury, and knowing what catheter resistances to target for further chronic studies, steps towards controlled retroperfusion and thus more efficient treatment options can be made for severe PAD patients.