TY - JOUR. T1 - Estrogen deficiency attenuates neovascularization in a murine model of hindlimb ischemia. AU - Matsubara, Kentaro. AU - Harada, Hirohisa. AU - Ando, Nobutoshi. AU - Watada, Susumu. AU - Obara, Hideaki. AU - Matsumoto, Kenji. AU - Kitagawa, Yuukou. PY - 2012/12. Y1 - 2012/12. N2 - Background: The possible relation between menopause and the development of peripheral arterial disease, especially lower extremity disease, has not been fully studied. To explore this issue, we investigated whether estrogen deficiency affected neovascularization in a murine model of hindlimb ischemia. Methods: Ischemia was surgically induced in one hindlimb of oophorectomized and control female BALB/c mice. Neovascularization in the ischemic hindlimbs was evaluated using laser Doppler blood flow analysis and capillary density analysis of the adductor muscle. The expression of endothelial nitric oxide synthase protein in the adductor muscle of the ischemic hindlimbs was assessed. Results: The plasma 17-β ...
The present study first demonstrates that ex vivo cell therapy, consisting of culture-expanded EPC transplantation, may be a novel therapy for diabetic neuropathy. The transplantation of cord blood-derived EPCs into unilateral hindlimb skeletal muscles reversed the impairment of sciatic MNCV and SNBF in the EPC-injected side of diabetic animal. The immunohistological study revealed that the number of the vessels was increased in the EPC-injected side of hindlimb skeletal muscle.. After the discovery of EPCs in adult peripheral blood in 1997, many experimental studies revealed that EPCs have a potent ability for neovascularization and that the transplantation of EPCs improves ischemic tissue (11,17). Because EPCs exist in bone marrow and cord blood and small percentages are found in peripheral blood, clinical trials of the transplantation of MNCs from bone marrow or peripheral blood were performed for the treatment of ischemic diseases. The Therapeutic Angiogenesis Using Cell Transplantation ...
Objective- Recent clinical studies of therapeutic neovascularization using angiogenic growth factors demonstrated smaller therapeutic effects than those reported in animal experiments. We hypothesized that nanoparticle (NP)-mediated cell-selective delivery of statins to vascular endothelium would more effectively and integratively induce therapeutic neovascularization.. Methods and Results- In a murine hindlimb ischemia model, intramuscular injection of biodegradable polymeric NP resulted in cell-selective delivery of NP into the capillary and arteriolar endothelium of ischemic muscles for up to 2 weeks postinjection. NP-mediated statin delivery significantly enhanced recovery of blood perfusion to the ischemic limb, increased angiogenesis and arteriogenesis, and promoted expression of the protein kinase Akt, endothelial nitric oxide synthase (eNOS), and angiogenic growth factors. These effects were blocked in mice administered a nitric oxide synthase inhibitor, or in eNOS-deficient ...
The present study used a gene-targeting strategy to establish a novel role for EC-derived MMP-2 in neovascularization. We provided both in vitro and in vivo evidence that MMP-2 promotes the migratory and angiogenic capacity of cultured aortic EC and BM-derived EPC-like c-Kit+ cells and further neovessel growth. In line with recent studies indicating that certain MMPs are involved in EPC mobilization, our data underscore the critical role of MMP-2 in EPC mobilization into the circulation to support ischemia-induced neovascularization. The mechanisms underlying the impairment of ischemia-induced neovascularization in MMP-2-deficient mice are schematically represented in supplemental Figure X.. The capillary density, collateral artery, and blood flow in the ischemic tissues were much lower in MMP-2−/− mice than in MMP-2+/+ mice, despite the compensatory increase of MMP-9 expression and its activity and TIMP-1 expression. This suggested that endogenous MMP-2 contributes to ischemia-induced ...
In the present study, we demonstrated in vivo that AM infusion or MNC transplantation alone induced angiogenesis in a rat model of hindlimb ischemia, the combination of AM infusion and MNC transplantation enhanced MNC-induced angiogenesis, and AM increased the number of MNC-derived vWF-positive cells and generated α-SMA-positive vascular structures. We also demonstrated in vitro that AM inhibited serum starvation-induced MNC apoptosis, promoted MNC adhesiveness to an HUVEC monolayer, increased the number of MNC-derived EPCs, and stimulated SMC migration.. MNC transplantation causes therapeutic angiogenesis by supplying EPCs and multiple angiogenic cytokines such as VEGF.3,4 The present study showed that local infusion of AM significantly increased blood perfusion and capillary density in ischemic hindlimb muscle. Furthermore, a combination of AM infusion and MNC transplantation significantly increased blood perfusion and capillary density of the ischemic hindlimb compared with MNC ...
TY - JOUR. T1 - NADPH oxidase 2 regulates bone marrow microenvironment following hindlimb ischemia. T2 - Role in reparative mobilization of progenitor cells. AU - Urao, Norifumi. AU - McKinney, Ronald D.. AU - Fukai, Tohru. AU - Ushio-Fukai, Masuko. PY - 2012/5/1. Y1 - 2012/5/1. N2 - Bone marrow (BM) microenvironment, which is regulated by hypoxia and proteolytic enzymes, is crucial for stem/progenitor cell function and mobilization involved in postnatal neovascularization. We demonstrated that NADPH oxidase 2 (Nox2)-derived reactive oxygen species (ROS) are involved in postischemic mobilization of BM cells and revascularization. However, role of Nox2 in regulating BM microenvironment in response to ischemic injury remains unknown. Here, we show that hindlimb ischemia of mice increases ROS production in both the endosteal and central region of BM tissue in situ, which is almost completely abolished in Nox2 knockout (KO) mice. This Nox2-dependent ROS production is mainly derived from Gr-1+myeloid ...
Objective Oxygen delivery, underpinned by vascular tone, is the principle limiting factor in the study of skeletal muscle physiology, particularly during muscle contraction. The aim of this study was to develop an autologous perfused rat hind limb preparation for the study of skeletal muscle contractile function. Methods Adult Wistar rats were surgically prepared using a by-pass system for pump-controlled arterial blood flow to, and venous return from the hind limb during periods of quiescence and twitch contraction of the gastrocnemius-plantaris-soleus muscle bundle. Results During rest, hind limb perfusion pressure (102 ± 5 mmHg) was not different to systemic arterial pressure (99 ± 4 mmHg). Hind limb pressure was responsive to vasoconstrictors and vasodilators (±50 mmHg). The arterial PO2 (100 ± 3 mmHg), O2 saturation, and acid-base balance (pH: 7.42 ± 0.01) contributed to resting hind limb (a-v)O2 difference (4.8 ± 0.5 mL/100 mL) and VO2 (0.31 ± 0.03 μmol/g/min wet weight). Repetitive
Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α ) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P , 0 ...
Canine Hindlimb Muscles Test your knowledge on this science quiz to see how you do and compare your score to others. Quiz by Kirkypls42
Bone marrow mononuclear cells (BM MNC), specifically monocytic cells, can augment new blood vessel formation in a hind limb ischemia model of angiogenesis. Approaches to track the activity of such cells in vivo with MRI have employed labeling with ferrous compounds to provide MR contrast effects. We propose a new labeling method utilizing perfluorocarbon nanoparticles (PFC NP) that avoids the ubiquitous background water signal and the susceptibility artifact that accompanies iron oxide particles, and also allows quantification of the signal to determine nanoparticle concentration,. The advantage of PFC NP is their inherent fluorine signal that can be analyzed using 19F MR imaging and spectroscopy. BM MNCs isolated from the femur and tibia of donor mice were labeled in 6 hours without the use of transfection agents and without detriment to viability (,95% via dye exclusion). Analysis by flow cytometry showed that the PFC NP labeling efficiency for the Gr-1+ cells and CD11b+ cells (both monocytic ...
TY - GEN. T1 - Advances in Pulsed Doppler Methods for Peripheral Perfusion Imaging. AU - Insana, Michael F.. AU - Zhu, Yang. AU - Kim, Min Woo. AU - Dobrucki, L. Wawrzyniec. PY - 2019/10. Y1 - 2019/10. N2 - We report on methods for imaging blood perfusion in peripheral skeletal muscle tissues without exogenous contrast enhancement. The ultimate goal is to provide new tools for monitoring the development and treatment of peripheral artery disease (PAD) in diabetic patients. Sparse ultrasonic pulse-echo acquisitions are arranged into 3-D echo data arrays. Each array is decomposed using higher-order singular value decomposition (HOSVD) methods to uncouple echo sources for clutter filtering before signal power is mapped into power Doppler (PD) images. This method enables further segmentation of the blood-echo power into flow maps covering non-overlapping velocity ranges. Our method is compared with other imaging modalities that together assess the recovery in a murine hindlimb ischemia model of ...
TY - JOUR. T1 - Role of nox2-based NADPH 0xidase in bone marrow and progenitor cell function involved in neovascularization induced by hindlimb ischemia. AU - Urao, Norifumi. AU - Inomata, Hyoe. AU - Razvi, Masooma. AU - Kim, Ha Won. AU - Wary, Kishore. AU - McKinney, Ronald. AU - Fukai, Tohru. AU - Ushio-Fukai, Masuko. PY - 2008/7/18. Y1 - 2008/7/18. N2 - Bone marrow (BM) is the major reservoir for endothelial progenitor cells (EPCs). Postnatal neovascularization depends on not only angiogenesis but also vasculogenesis, which is mediated through mobilization of EPCs from BM and their recruitment to the ischemic sites. Reactive oxygen species (ROS) derived from Nox2-based NADPH oxidase play an important role in postnatal neovascularization; however, their role in BM and EPC function is unknown. Here we show that hindlimb ischemia of mice significantly increases Nox2 expression and ROS production in BM-mononuclear cells (BMCs), which is associated with an increase in circulating EPC-like cells. ...
TY - JOUR. T1 - Detection of extracellular genomic DNA scaffold in human thrombus. T2 - Implications for the use of deoxyribonuclease enzymes in thrombolysis. AU - Oklu, Rahmi. AU - Albadawi, Hassan. AU - Watkins, Michael T.. AU - Monestier, Marc. AU - Sillesen, Martin. AU - Wicky, Stephan. PY - 2012/5. Y1 - 2012/5. N2 - Purpose: Mechanisms underlying transition of a thrombus susceptible to tissue plasminogen activator (TPA) fibrinolysis to one that is resistant is unclear. Demonstration of a new possible thrombus scaffold may open new avenues of research in thrombolysis and may provide mechanistic insight into thrombus remodeling. Materials and Methods: Ten human thrombus samples were collected during cases of thrombectomy and open surgical repair of abdominal aortic aneurysms (five samples , 3 d old and five samples , 1 y old). Additionally, an acute murine hindlimb ischemia model was created to evaluate thrombus samples in mice. Human sections were immunostained for the H2A/H2B/DNA complex, ...
Lee CW, Stabile E, Kinnaird T, Shou M, Devaney JM, Epstein SE, Burnett MS. Temporal patterns of gene expression after acute hindlimb ischemia in mice: insights into the genomic program for collateral vessel development. J Am Coll Cardiol. 2004 Feb 04; 43(3):474-82 ...
The domestic dog is believed to be a direct descendant from modern wolves. Dogs have been bred as pets for thousands of years with the earliest known domestication taking place as long as 12,000 years ago. Today, dogs serve man in many ways: as guides, search and rescue, for hunting purposes, to sniff out drugs or othe
Three-Dimensional Cell Aggregates Composed of HUVECs and cbMSCs for Therapeutic Neovascularization in a Mouse Model of Hindlimb Ischemia
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1-(3,5-dimethyl-4-propionylamino)benzoyl-4-(N-methyl-2-phenylethyl)aminopiperidine: a canine hindlimb vasodilator; structure in first source
Hind-limb function indicated a progressive decline in function of ischemia-reperfusion IR controls. The scores of Sham group at the same time point were higher
Study. U251 cells (56106) were injected into the right hind flank subcutaneously. When the tumors reached a volume of ,150 mm3 they were randomized into one of
TY - JOUR. T1 - The impact of pelvic lateral rotation on hindlimb kinematics and stride-length in the red-legged running frog, Kassina maculata. AU - Collings, Amber. AU - Porro, Laura. AU - Hill, Cameron. AU - Richards, Christopher T.. PY - 2019/5/8. Y1 - 2019/5/8. N2 - Some frog species, such as Kassina maculata (red-legged running frog), use an asynchronous walking/running gait as their primary locomotor mode. Prior comparative anatomy work has suggested that lateral rotation of the pelvis improves walking performance by increasing hindlimb stride length; however, this hypothesis has never been tested. Using non-invasive methods, experimental high-speed video data collected from eight animals were used to create two three-dimensional kinematic models. These models, each fixed to alternative local anatomical reference frames, were used to investigate the hypothesis that lateral rotation of the mobile ilio-sacral joint in the anuran pelvis plays a propulsive role in walking locomotion by ...
The main result of this study is that CXCR3 expression positively modulates ischemia-induced neovascularization, likely through modulation of inflammatory cell infiltration within the ischemic area. This study also extends previous results on the role of MCP-1 in this process and shows a significant impairment in postischemic neovascularization in MCP-1-deficient mice.. Classically, inflammatory cells have been shown to promote neovascularization through various mechanisms, including production of angiogenic factors, secretion of proinflammatory cytokines, and increased matrix degradation.7-9 LPS-induced monocyte accumulation promotes vessel growth, whereas absence of macrophages is associated with a deficient neovascularization response.10,11 A specific role of T cells in this setting was also suggested in Nude mice and in CD4-deficient mice, which exhibit a marked reduction in the angiogenic/arteriogenic process.4,5 In this study, we showed that CXCR3 and its ligands CXCL-10 and CXCL-9 were ...
TY - JOUR. T1 - A transgenic rat expressing green fluorescent protein (GFP) in peripheral nerves provides a new hindlimb model for the study of nerve injury and regeneration. AU - Moore, Amy M.. AU - Borschel, Gregory H.. AU - Santosa, Katherine B.. AU - Flagg, Eric R.. AU - Tong, Alice Y.. AU - Kasukurthi, Rahul. AU - Newton, Piyaraj. AU - Yan, Ying. AU - Hunter, Daniel A.. AU - Johnson, Philip J.. AU - Mackinnon, Susan E.. PY - 2012/2/1. Y1 - 2012/2/1. N2 - Background: In order to evaluate nerve regeneration in clinically relevant hindlimb surgical paradigms not feasible in fluorescent mice models, we developed a rat that expresses green fluorescent protein (GFP) in neural tissue. Methods: Transgenic Sprague-Dawley rat lines were created using pronuclear injection of a transgene expressing GFP under the control of the thy1 gene. Nerves were imaged under fluorescence microscopy and muscles were imaged with confocal microscopy to determine GFP expression following sciatic nerve crush, ...
Gene therapy stimulating the growth of blood vessels is considered for the treatment of peripheral and myocardial ischemia. Here we aimed to achieve angiogenic synergism between vascular endothelial growth factor-A (VEGF-A, VEGF) and fibroblast growth factor 4 (FGF4) in murine normoperfused and ischemic limb muscles. Adeno-associated viral vectors (AAVs) carrying β-galactosidase gene (AAV-LacZ), VEGF-A (AAV-VEGF-A) or two angiogenic genes (AAV-FGF4-IRES-VEGF-A) were injected into the normo-perfused adductor muscles of C57Bl/6 mice. Moreover, in a different experiment, mice were subjected to unilateral hindlimb ischemia by femoral artery ligation followed by intramuscular injections of AAV-LacZ, AAV-VEGF-A or AAV-FGF4-IRES-VEGF-A below the site of ligation. Post-ischemic blood flow recovery was assessed sequentially by color laser Doppler. Mice were monitored for 28 days. VEGF-A delivered alone (AAV-VEGF-A) or in combination with FGF4 (AAV-FGF4-IRES-VEGF-A) increased the number of capillaries in normo
Subcutaneous infusion of ANG II at 450, but not 150, ng·kg−1·min−1 for 14 days elevated baseline MAP compared with sham rats. We found that RSNA and pressor responses to continuous contraction and the RSNA response to intermittent contraction were significantly larger in ANGII450 rats than those in sham rats. We also found that, in ANGII450 rats, intra-arterial injection into the hindlimb circulation of tempol, a membrane-permeable SOD mimetic, reduced RSNA, arterial pressure, and HR responses to continuous contraction as well as the RSNA response to intermittent contraction. Tiron, another SOD mimetic, mirrored the effect of tempol; intra-arterial injection of Tiron into the hindlimb circulation reduced RSNA and pressor responses to continuous contraction of the hindlimb muscles of hypertensive rats. In sham and ANGII150 rats, on the other hand, tempol injected intra-arterially did not modulate RSNA and cardiovascular responses to either continuous or intermittent static contraction. ...
The kinematics of basilisk water running varied considerably. Basilisks weighing up to 20 g sometimes exhibited an aerial phase in a run. Yet it was unclear which variables other than mass were responsible for this variability. In general, the forearms `windmill during a run but to different extents. When basilisks ran with a large trunk angle to the water, they extended their arms forwards with minimal rotation around the shoulder. By contrast, when the trunk was held at ∼45° to the water - the much more common body posture - basilisks arm movements matched directions with the leg on the contralateral side. In other runs, the arms moved with a slight delay to the contralateral hindlimb and were sometimes so delayed that it nearly matched the movements with the hindlimb on the same side. Windmilling the forearms may serve to counteract torques placed on the body during a stride, as have been reported in human studies to explain the pendulum-like motion of the arms during walking (Li et al., ...
... Barnes B.R., T.C. Selix, D.C. Wright, and B.W. Craig. Ball State University, Muncie, IN.The purpose of this investigation was to determine the effects of a glucocorticoid-antagonist (RU486) on insulin-like-growth-factor-1 (IGF1)stimulated glucose transport following two weeks of hindlimb suspension (HS) on 100 gm male rats. After two weeks of HS and/or oral RU486 administration the animals were anesthetized, and the soleus (SOL) and extensor digitorum longus (EDL) muscles isolated and clamped at their resting length. Following an incubation series to prepare the muscle, the muscle was incubated in radioactive 3-O-methylglucose for 10 min. in the presence/absence of 75 ng/ml of IGF1, digested with 0.5 NaOH, and the amount of glucose transported measured. Two weeks of RU486 treatment significantly (P:5 0.05) elevated IGF1-stimulated glucose transport of SOL (0.576 ± 0.071 vs ...
Advanced age is a major risk factor of peripheral artery disease. We examined the effects of the aging-suppressor gene klotho on angiogenesis in response to ischemia by introducing ischemic hindlimb model in mice heterozygously deficient for the klotho gene and in wild type mice. Blood flow recovery …
We have characterized the early stages of murine hindlimb morphogenesis in the legless (lgl)mutant and non-mutant littermates. Initially the entire ventral ectoderm expresses many genetic markers characteristic of the AER (en-1, fgf-8, msx-2, dlx-2, cd44, and cx-43). Subsequently, the expression dom …
This is the first study showing the physiological role of the interaction between the non-NMDA receptor (AMPA) activation and NO produced endogenously in the NTS of conscious rats. The present data show that inhibition of NO production within the NTS changes the hemodynamic responses elicited by AMPA receptor stimulation.. Activation of the AMPA receptor in the NTS of conscious rats induces an initial reduction in hindquarter blood flow that is followed by a large increase (9). Increased blood flow is due to hindquarter vasodilation. The origin and pathway of this vasodilation was not clear, but studies of Davisson et al. (6, 7) suggested a neurogenic hindquarter vasodilation mediated by release of preformed stores of nitrosyl factors after sympathetic stimulation. Colombari et al. (4) showed a hindquarter vasodilation elicited by activation of glutamatergic receptors in the NTS that was abolished after systemic l-NAME administration. The systemic administration of l-NAME probably blocked NOS in ...
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My 8 yo beagle started limping suddenly on his right hind leg. He didnt appear to be in any pain and it got better after a couple of weeks! Now, he is suddenly limping on his left hind leg and can b...
Structural and functional anatomy and biomechanics of the hindlimb in general, and in specific for the art. coxae, the art. genus, the art. tarsales, the art metatarso-phalangealis, the art. interphalangealea proximalis et distales, the ossae sesamoideae, and the patellae. The heamodynamic relations and the osteopathic relevance, of the art. coxae. The biomechanics and osteopathic relevance of the menisci. Introduction to the examination and normalizing technics for the hindlimb. Find out more » ...
Ability, B-cells, Blood, Cells, Enzyme Immunoassay, Flow Cytometry, Hindlimb, Hindlimb Unloading, Immunity, Immunoassay, Infection, Infections, Leukocyte, Lymphocyte, Mice, Nervous System, Plasma, Population, Rodent, Spaceflight
Supplementary Material for: VEGF and IGF Delivered from Alginate Hydrogels Promote Stable Perfusion Recovery in Ischemic Hind Limbs of Aged Mice and Young Rabbits
(13)N-ammonia PET as a measurement of hindlimb perfusion in a mouse model of peripheral artery occlusive disease. (13)N-ammonia PET as a measurement of hindlimb perfusion in a mouse model of peripheral artery occlusive disease
REASONS FOR PERFORMING STUDY: The compensatory mechanisms of horses with weightbearing hindlimb lameness are still not fully understood. HYPOTHESIS: That weightbearing, unilateral hindlimb lameness would not only alter stride characteristics to diminish structural stress in the affected limb but also induce compensatory load adjustments in the other supporting limbs. OBJECTIVE: To document the load and time shifting mechanisms of horses with unilateral weightbearing hindlimb lameness. METHODS: Reversible lameness was induced in 8 clinically sound horses by applying a solar pressure model. Three degrees of lameness (subtle, mild and moderate) were induced and compared with the nonlame (sound) control measurement. Vertical ground reaction forces were recorded for all 4 limbs simultaneously on an instrumented treadmill. RESULTS: Compared to the sound situation, moderate hindlimb hoof lameness induced a decrease in stride duration (-3.3%) and stride impulse (-3.1%). Diagonal impulse decreased ...
This study combines two well-known vascular research models, hyperoxia and hind limb ischemia, aiming to better characterize capacities of the hyperoxia challenge. We studied two groups of C57/BL6 male mice, a control (C) and a hind limb ischemia (HLI) group. Perfusion from both limbs was recorded in all animals by laser Doppler techniques under an oxygen (O 2) saturated atmosphere, once for control and, during 35 days for the HLI group. We used a third set of normoxic animals for HLI morphometric control. The expected variability of responses was higher for the younger animals. In the HLI group, capillary density normalized at Day 21 as expected, but not microcirculatory physiology. In the operated limb, perfusion decreased dramatically following surgery (Day 4), as a slight reduction in the non-operated limb was also noted. Consistently, the response to hyperoxia was an increased perfusion in the ischemic limb and decreased perfusion in the contralateral limb. Only at Day 35, both limbs exhibited
We selected the rat model of a brain lesion induced by photochemically initiated thrombosis(PIT) through platelet aggregation. The technique involved in this model is simple enough to design the brain lesion as focal and uniform, and the hemiparesis of the hindlimb, induced by injury to the unilateral motor cortex, recovers completely by the 10th day with few individual differences after operation. The purpose of this study was to examine whether using the stem cell transplantation or the mesenchymal stem cell transplantation promotes motor recovery after brain damage in this PIT model. After recovery of left hindlimb function caused by a right sensorimotor cortex lesion, a lesion was induced photochemically in the left sensorimotor cortex as a second PIT and the beam-walking score was recorded for right hindlimb function. As a result, these two methods were not able to promote motor recovery after brain damage in this PIT model. ...
After complete spinal transection in adult rats, careful combinations of pharmacological and physical therapies create a novel cortical sensorimotor circuit that may bypass the lesion through biomechanical coupling, allowing animals to recover unassisted hindlimb locomotion.
Background. Preclinical perfusion studies are useful for the improvement of diagnosis and therapy in dermatologic, cardiovascular and rheumatic human diseases. The Laser Doppler Perfusion Imaging (LDPI) technique has been used to evaluate superficial alterations of the skin microcirculation in surgically induced murine hindlimb ischemia. We assessed the reproducibility and the accuracy of LDPI acquisitions and identified several critical factors that could affect LDPI measurements in mice. Methods. Twenty mice were analysed. Statistical standardisation and a repeatability and reproducibility analysis were performed on mouse perfusion signals with respect to differences in body temperature, the presence or absence of hair, the type of anaesthesia used for LDPI measurements and the position of the mouse body. Results. We found excellent correlations among measurements made by the same operator (i.e., repeatability) under the same experimental conditions and by two different operators (i.e.,
Substance P (SP) is a therapeutic peptide that has been widely used to induce angiogenesis and tissue regeneration. However, its therapeutic efficacy is often limited due to rapid degradation in vivo and a short half-life (1 min) after systemic administration. In the present study, we chemically modified SP with polyethylene glycol (PEG) to generate long-lasting formulations with increased stability and extended retention time in vivo and evaluated their ability to enhance therapeutic angiogenesis. Compared to the unmodified SP, PEGylated SP (PEG-SP) exhibited significantly increased half-life in vivo ('360-fold increase in normal mouse and (similar to)120-fold increase in diabetic mouse). Systemic injection of PEG SP led to a marked increase in therapeutic efficacy and angiogenesis in diabetic hindlimb ischemia, as evident from the remarkable improvement in salvage of ischemic limb and recovery of blood perfusion in diabetic mice with limb ischemia. These formulations increased endogenous ...
Our ability to link amplified arteriogenesis to a unique hemodynamic stimulus (ie, reversed flow with increase shear stress magnitude) was facilitated by the development of a LSF approach for mouse hindlimb collaterals.18 We developed that approach because, despite the known importance of hemodynamic stimuli in driving collateral development, there was a surprising lack of quantitative data on the hemodynamic changes within these arteries. This is likely because both the small size of the arteries (,100 μm) and the fact that different surgical models elicit arteriogenesis along different collateral pathways.2 Using LSF,18 we determined the occurrence of at least 3 distinct hemodynamic conditions in these collateral vessels: a nonreversed increase in shear stress near the feeding entrance to the collateral loop, an increase in shear stress from low/oscillating flow to sustained high shear stress at the central anastomotic region, and an increase in shear stress but in a reversed direction at the ...
Effects of 24-72 h of hindlimb suspension on body and muscle weights (a), muscle-to-body weight ratio (b), and parameters (c) of rat soleus twitch tensions.
Video articles in JoVE about bone density include Scanning Skeletal Remains for Bone Mineral Density in Forensic Contexts, Semiautomated Longitudinal Microcomputed Tomography-based Quantitative Structural Analysis of a Nude Rat Osteoporosis-related Vertebral Fracture Model, Subject-specific Musculoskeletal Model for Studying Bone Strain During Dynamic Motion, Establishment of a Segmental Femoral Critical-size Defect Model in Mice Stabilized by Plate Osteosynthesis, A Method to Estimate Cadaveric Femur Cortical Strains During Fracture Testing Using Digital Image Correlation, Longitudinal Evaluation of Mouse Hind Limb Bone Loss After Spinal Cord Injury using Novel, in vivo, Methodology, Peptides from Phage Display Library Modulate Gene Expression in Mesenchymal Cells and Potentiate Osteogenesis in Unicortical Bone Defects, Preparation of Herbal Medicine: Er-Xian Decoction and Er-Xian-containing Serum for In Vivo and In Vitro Experiments, Tissue Characterization after a New
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Video articles in JoVE about long term care include Using a Real-Time Locating System to Measure Walking Activity Associated with Wandering Behaviors Among Institutionalized Older Adults, Using Retinal Imaging to Study Dementia, Oral Health Assessment by Lay Personnel for Older Adults, Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury.
Pentobarbital sodium-anesthetized animals were injected with 0.4 ml of 0.1% bovine serum albumin with 0 or 0.1 U bovine insulin/rat via the dorsal vein of the penis. A preliminary study indicated that the insulin-stimulated activity of Akt1 kinase peaked in both soleus and plantaris muscles at 5 min and remained above control level for at least 15 min (data not shown). This time course is in agreement with studies by Cross et al. (10). Therefore, soleus and plantaris muscles were quickly excised at 5 min after the intravenous injection. In each rat, the muscles were excised only from one hindlimb, either the denervated hindlimb or the contralateral sham hindlimb, to ensure that the muscles were removed exactly at the 5-min interval. Each excised muscle was immediately frozen in liquid nitrogen and subsequently kept at −85°C until further use. Each muscle was powdered under liquid nitrogen within 24 h. The powder was transferred into a 6-ml polypropylene tube containing 0.5 ml of ...
Almost simultaneously with the occurrence of the specific complaints we see the disappearing pulse curves (see Figure 2). A simple test that may be performed by medical personnel accompanying cyclists is the measurement of the ankle / arm systolic blood pressure ratio after maximum effort. An appropriate cycle ergometer is after all usually available. This allowed the rider to undergo a rising load protocol, with the typical cycling position. The cyclist is instructed to continue up to the occurrence of the known symptoms. Prior to the test, one measures the systolic blood pressures of brachial artery (arm) and the two posterior arteries tibiales (leg) at rest. Immediately after the breakdown of the exercise test the rider lies on the examination couch and the aforementioned systolic blood pressures are recorded every minute until the rest values are reached again. A significantly reduced ankle/arm systolic blood pressure ratio in the symptomatic leg in comparison with the free leg during ...
Diabetes in the United States today is an explosive major public health issue that directly impacts cardiovascular morbidity and mortality. One major reason for...