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Capillary Density (capillary + density)
Selected AbstractsEffect of smoking on the gingival capillary density: assessment of gingival capillary density with orthogonal polarization spectral imagingJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2005J. A. Lindeboom Abstract Objectives: Microvascular changes because of smoking are frequently presumed in models because of the negative effect of smoking portrayed on the microcirculation. We hypothesized that cigarette smoke might lead to a decrease in gingival capillary density. Materials and Methods: Capillary density was assessed with orthogonal polarization spectral (OPS) imaging, a technique using special optics by which a virtual light source is created at a depth of 1 mm within the mucosa. The light is absorbed by haemoglobin, resulting in an image of the capillaries in negative contrast. The gingival capillary density was measured in 20 healthy male dental students with a mean age of 25. Ten of the students were smokers and 10 were non-smokers. In each subject six images of the right maxillary pre-molar region were obtained, and the mean gingival capillary density was determined through the use of K&K software technology. Results: The mean capillary density in smokers was 69.3±8.9 capillaries per visual field compared with a mean capillary density in non-smokers of 60.6±5.4 (p=0.33). Conclusion: No significant differences were found between the gingival capillary density of smokers and non-smokers. [source] Functional Capillary Rarefaction in Mild Blood Pressure ElevationCLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2008Cynthia Cheng Abstract Capillary rarefaction is described in patients with moderate-to-severe hypertension. The study objective was to determine if structural and/or functional capillary rarefaction is detectable and associated with endothelial dysfunction in patients with mild blood pressure elevation (HBP: Systolic blood pressure 130,160 mm Hg). Capillary density was quantified by direct capillaroscopy in 110 nondiabetic black and non-black subjects. Endothelial function was quantified by plethysmographic measures of flow-mediated vasodilation. Compared to normotensives (NBP: N = 90), functional capillary rarefaction was detected in HBP (N = 20; p < 0.001). Functional capillary density measures correlated with endothelial function (p < 0.001). Functional, but not structural, capillary rarefaction is detectable and associated with endothelial dysfunction in both black and non-black individuals with mild blood pressure elevation. [source] Enhancement of Viability of Fat Grafts in Nude Mice by Endothelial Progenitor CellsDERMATOLOGIC SURGERY, Issue 12 2006CHENGGANG YI MD BACKGROUND A recent discovery showed that endothelial progenitor cells (EPCs) could augment collateral vessel growth to ischemic tissues. OBJECTIVE The objective was to demonstrate the effects of EPCs on the vasculogenesis and survival of free transplanted fat tissues in nude mice. METHODS EPCs from human donors were cultured in vitro for 7 days. Human fat tissues were injected subcutaneously into the scalps of 20 6-week-old nude male mice. EPCs stained with CM-DiI were mixed with the transplanted fat tissues and injected into the mice. EBM-2 medium was used as control group. The animals were euthanized 15 weeks after the procedure. Graft volume were measured, and histologic evaluation was performed. The central part of fat tissues was histologically evaluated 15 weeks after the fat injection. RESULTS The survival volume of the experimental group was significantly greater than that of the control group (p< .05). Less cyst formation and fibrosis was obtained in the experimental group. Histologic evaluation of the central part of fat tissues 15 weeks after the fat injection showed that capillary densities increased markedly in the experimental group mice. CONCLUSION The results indicate that EPCs have the ability to enhance the survival and the quality of the transplanted fat tissues. [source] Muscle fibre size and capillarity in Korean diving womenACTA PHYSIOLOGICA, Issue 2 2003K. A. Bae Abstract Aim:, Effects of prolonged habitual cold-water immersion on fibre size and capillarity in vastus lateralis muscle were studied in human beings. The hypothesis tested in the present study was that cold acclimatized human skeletal muscle would have reduced muscle fibre size and higher capillarity, favouring the idea of efficacy of recruitment under cold environment. Methods:, Ten women breath-hold divers (BHDs) and 10 active women (controls CONs) participated in this study. Muscle biopsy was obtained from vastus lateralis and determined fibre type composition and capillary density. Results: A major finding was that all BHDs revealed a markedly smaller cross-sectional area (CSA) in all fibre types than the CONs, or even than any other morphological data reported in previous investigations. Furthermore, mean CSA of type II fibre (range 1205,2766 ,m2) was much smaller than type I fibre (2343,4327 ,m2). The number of capillaries per fibre in different fibre types in the BHDs was higher than in the CONs (P < 0.001), and diffusional area was smaller in type II fibres than in type I fibres (P < 0.001). The BHDs and the CONs have similarity in the percentage of type I fibres, but type II fibre was predominant in both groups. Interestingly the proportion of type IIx fibre in the BHDs was higher (31%) than in the CONs (22%). No significant difference was found in the thigh circumference between the groups. Conclusion:, The present study demonstrates that prolonged habitual cold-water immersion may induce a decrease in fibre size and an increase in capillarity in human skeletal muscle. [source] Changes in capillary luminal diameter in rat soleus muscle after hind-limb suspensionACTA PHYSIOLOGICA, Issue 4 2000Kano This study examined the time course change of the capillary luminal diameter and the number of capillaries in the rat soleus muscle during hind-limb suspension. Male Wistar rats were divided into 1 and 3 weeks of hind-limb suspension (HS) groups (HS-1 and HS-3). The HS groups were compared with age-matched control groups. All morphometric parameters with respect to capillary and muscle fibre cross-sectional area were determined in perfusion-fixed soleus muscles. After 1 and 3 weeks of hind-limb suspension, the mean muscle fibre cross-sectional area was significantly decreased in HS-1 (,32.0%) and HS-3 (,59.3%) compared with age-matched control groups. Despite a lower capillary-to-fibre ratio (HS-1, ,19.3%; HS-3, ,21.2%), the capillary density was unchanged in HS-1 and significantly increased in HS-3 compared with age-matched control groups. The mean capillary luminal diameter was significantly smaller in HS-1 (,19.9%) and HS-3 (,21.9%) than in the age-matched control groups. The capillary-to-fibre perimeter ratio which indicates the capillary surface area available for gas exchange between blood and tissue did not significantly differ between control groups and HS groups. In conclusion, the morphometrical adaptations in rat soleus with the suspension involved changes in both the capillary luminal diameter and number of capillaries, and the change in capillary surface area was proportional to the degree of muscle atrophy in HS groups. [source] Gene targeted ablation of high molecular weight fibroblast growth factor-2DEVELOPMENTAL DYNAMICS, Issue 2 2009Mohamad Azhar Abstract Fibroblast growth factor-2 (FGF2) is produced as high molecular weight isoforms (HMW) and a low molecular weight isoform (LMW) by means of alternative usage of translation start sites in a single Fgf2 mRNA. Although the physiological function of FGF2 and FGF2 LMW has been investigated in myocardial capillarogenesis during normal cardiac growth, the role of FGF2 HMW has not been determined. Here, we report the generation of FGF2 HMW-deficient mice in which FGF2 HMW isoforms are ablated by the Tag-and-Exchange gene targeting technique. These mice are normal and fertile with normal fecundity, and have a normal life span. Histological, immunohistochemical, and morphometric analyses indicate normal myocardial architecture, blood vessel, and cardiac capillary density in young adult FGF2 HMW-deficient mice. These mice along with the FGF2- and FGF2 LMW-deficient mice that we have generated previously will be very useful for elucidating the differential functions of FGF2 isoforms in pathophysiology of cardiovascular diseases. Developmental Dynamics 238:351,357, 2009. © 2008 Wiley-Liss, Inc. [source] Chronic Hypoxia Induces Prolonged Angiogenesis in Skeletal Muscles of RatEXPERIMENTAL PHYSIOLOGY, Issue 3 2002D. Deveci Skeletal muscle capillarity and fibre cross-sectional area were investigated within and between diaphragm (Diaph), extensor digitorum longus (EDL), soleus (SOL) and tibialis anterior (TA) muscles of control and chronic hypoxic (12% O2 for 6 weeks) adult male Wistar rats (final body mass ,355 g). Cryostat sections were stained for alkaline phosphatase activity to depict all capillaries, and for succinic dehydrogenase to demonstrate regional differences in oxidative capacity within the muscles. Hypoxia-induced angiogenesis occurred in all muscles (P < 0.01), with capillary-to-fibre ratio (C:F) being higher in the more active and oxidative muscles, Diaph (27%) and SOL (26%), than phasically active and glycolytic muscles, TA (21%) and EDL (15%). Diaph, SOL and EDL maintained fibre size, and hence showed an increased capillary density (CD) and reduced intramuscular diffusion distance (DD), whereas TA showed fibre hypertrophy and maintained CD and DD compared to control muscles. The extent of angiogenesis among different regions of muscle varied so as to suggest that muscle fibre size has an additional influence on capillary growth during chronic systemic hypoxia, which is progressive over an extended period of systemic hypoxia. [source] Differential Effects of Cold Exposure on Muscle Fibre Composition and Capillary Supply in Hibernator and Non-Hibernator RodentsEXPERIMENTAL PHYSIOLOGY, Issue 5 2001S. Egginton Changes in the composition of fibre types and the capillary supply of skeletal muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8-10 weeks of cold exposure and reduced photoperiod (10 °C, 1 h light-23 h dark). Muscle mass decreased in both species (by 12% and 17%, respectively). Following acclimation to cold there were no specific changes in fibre cross-sectional area (FCSA) in rats, whereas in hamsters there was a substantial atrophy of Type II, but not Type I fibres. In rat muscle there was little difference between the two groups in average capillary to fibre ratio (C:F) (1.76 ± 0.15, normothermia, N; 1.69 ± 0.05, hypothermia, H) and average capillary density (CD) (188 ± 14 mm,2, N; 201 ± 12 mm -2, H). Similarly, the average C:F was unaltered in hamsters (2.75 ± 0.11, N; 2.72 ± 0.15, H), although the 30% smaller fibre size observed with hypothermia resulted in a corresponding increase in average CD, to 1539 ± 80 mm,2 (P < 0.01). However, there was a coordinated regional adaptation to cold exposure in hamsters resulting in capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative core. Following acclimation of rats to cold there was a reduction in the supply area of individual vessels (capillary domain), particularly in the cortex (9310, N; 8938 ,m2, H; P < 0.05). In contrast, hypothermic hamsters showed only a small decrease in mean domain area in the cortex (948 ,m2, N; 846 ,m2, H; n.s.) but a marked reduction in the core (871 ,m2, N; 604 ,m2, H; P < 0.01). Rats showed little or no change in local capillary supply (LCFR) to fast fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a simulated onset of winter rats maintain FCSA and capillary supply as part of an avoidance strategy, whereas hamsters increase muscle capillarity in part as a consequence of disuse atrophy. [source] Characterisation of human soft palate muscles with respect to fibre types, myosins and capillary supplyJOURNAL OF ANATOMY, Issue 2 2000PER S. STÅL Four human soft palate muscles, and palatopharyngeus, the uvula, the levator and tensor veli palatini were examined using enzyme-histochemical, immunohistochemical and biochemical methods and compared with human limb and facial muscles. Our results showed that each palate muscle had a distinct morphological identity and that they generally shared more similarities with facial than limb muscles. The palatopharyngeus and uvula muscles contained 2 of the highest proportions of type II fibres ever reported for human muscles. In contrast, the levator and tensor veli palatini muscles contained predominantly type I fibres. A fetal myosin heavy chain isoform (MyHC), not usually found in normal adult limb muscles, was present in a small number of fibres in all palate muscles. The mean muscle fibre diameter was smaller than in limb muscles and the individual and intramuscular variability in diameter and shape was considerable. All palate muscles had a high capillary density and an unusually high mitochondrial enzyme activity in the type II fibres, in comparison with limb muscles. No ordinary muscle spindles were observed. The fibre type and MyHC composition indicate that the palatopharyngeus and uvula muscles are functionally involved in quick movements whereas the levator and tensor veli palatini muscles perform slower and more continuous contractions. The high aerobic capacity and the rich capillarisation suggest that the palate muscles are relatively fatigue resistant. Absence of ordinary muscle spindles indicates a special proprioceptive control system. The special morphology of the palate muscles may be partly related to the unique anatomy with only one skeletal insertion, a feature consistent with muscle work at low load and tension and which may influence the cytoarchitecture of these muscles. Other important factors determining the special morphological characteristics might be specific functional requirements, distinct embryological origin and phylogenetic factors. [source] Liposome-based vascular endothelial growth factor-165 transfection with skeletal myoblast for treatment of ischaemic limb diseaseJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1-2 2010Lei Ye Abstract The study aims to use cholesterol (Chol) + DOTAP liposome (CD liposome) based human vascular endothelial growth factor-165 (VEGF165) gene transfer into skeletal myoblasts (SkMs) for treatment of acute hind limb ischaemia in a rabbit model. The feasibility and efficacy of CD liposome mediated gene transfer with rabbit SkMs were characterized using plasmid carrying enhanced green fluorescent protein (pEGFP) and assessed by flow cytometry. After optimization, SkMs were transfected with CD lipoplexes carrying plasmid-VEGF165 (CD-pVEGF165) and transplanted into rabbit ischaemic limb. Animals were randomized to receive intramuscular injection of Medium199 (M199; group 1), non-transfected SkM (group 2) or CD-pVEGF165 transfected SkM (group 3). Flow cytometry revealed that up to 16% rabbit SkMs were successfully transfected with pEGFP. Based on the optimized transfection condition, transfected rabbit SkM expressed VEGF165 up to day 18 with peak at day 2. SkMs were observed in all cell-transplanted groups, as visualized with 6-diamidino-2-phenylindole and bromodeoxyuridine. Angiographic blood vessel score revealed increased collateral vessel development in group 3 (39.7 ± 2.0) compared with group 2 (21.6 ± 1.1%, P < 0.001) and group 1 (16.9 ± 1.1%, P < 0.001). Immunostaining for CD31 showed significantly increased capillary density in group 3 (14.88 ± 0.9) compared with group 2 (8.5 ± 0.49, P < 0.001) and group 1 (5.69 ± 0.3, P < 0.001). Improved blood flow (ml/min./g) was achieved in animal group 3 (0.173 ± 0.04) as compared with animal group 2 (0.122 ± 0.016; P= 0.047) and group 1 (0.062 ± 0.012; P < 0.001). In conclusion, CD liposome mediated VEGF165 gene transfer with SkMs effectively induced neovascularization in the ischaemic hind limb and may serve as a safe and new therapeutic modality for the repair of acute ischaemic limb disease. [source] The temporal course of mucoperiosteal flap revascularization at guided bone regeneration-treated implant sites: a pilot studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2009Dan M. J. Milstein Abstract Aims: To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. Material and Methods: A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging for assessment of capillary density during the course of mucoperiosteal flap wound healing for 6 weeks in patients receiving dental implants. Results: The greatest increase in capillary regeneration occurred in the early wound-healing phase, during weeks 1 and 2, and recovery to baseline was achieved between weeks 4 and 5. A comparison of adjacent OPS measurements indicated that differences between the time point immediately following administration of local anaesthesia and directly post-operatively ( p=0.002), between a directly post-operative time point and after 1 week (p=0.009), and between post-operative weeks 1 and 2 (p=0.036) were statistically significant. Conclusions: The early healing phase of mucoperiosteal flaps is characterized by rapid capillary regeneration. OPS imaging enabled the possibility to monitor and quantify the temporal development of mucoperiosteal flap revascularization following periodontal surgery. [source] Effect of smoking on the gingival capillary density: assessment of gingival capillary density with orthogonal polarization spectral imagingJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2005J. A. Lindeboom Abstract Objectives: Microvascular changes because of smoking are frequently presumed in models because of the negative effect of smoking portrayed on the microcirculation. We hypothesized that cigarette smoke might lead to a decrease in gingival capillary density. Materials and Methods: Capillary density was assessed with orthogonal polarization spectral (OPS) imaging, a technique using special optics by which a virtual light source is created at a depth of 1 mm within the mucosa. The light is absorbed by haemoglobin, resulting in an image of the capillaries in negative contrast. The gingival capillary density was measured in 20 healthy male dental students with a mean age of 25. Ten of the students were smokers and 10 were non-smokers. In each subject six images of the right maxillary pre-molar region were obtained, and the mean gingival capillary density was determined through the use of K&K software technology. Results: The mean capillary density in smokers was 69.3±8.9 capillaries per visual field compared with a mean capillary density in non-smokers of 60.6±5.4 (p=0.33). Conclusion: No significant differences were found between the gingival capillary density of smokers and non-smokers. [source] Tissue Distribution, Autoradiography, and Metabolism of 4-(2,-Methoxyphenyl)-1-[2, -[N -2,-Pyridinyl)- p -[18F]Fluorobenzamido]ethyl]piperazine (p -[18F]MPPF), a New Serotonin 5-HT1A Antagonist for Positron Emission TomographyJOURNAL OF NEUROCHEMISTRY, Issue 2 2000An In Vivo Study in Rats The in vivo behavior of 4-(2,-methoxyphenyl)-1-[2,-[N -(2,-pyridinyl)- p -[18F]fluorobenzamido]ethyl]-piperazine (p -[18F]MPPF), a new serotonin 5-HT1A antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p -[18F]MPPF and in vitro 8-hydroxy-2-(di- n -[3H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p -[18F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT1A receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p -[18F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT1A specificity of p -[18F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT1A binding sites in the brain. [source] Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcomaJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2008Saminathan S. Nathan Abstract We have previously shown that osteosarcomas (OS) have states of increased interstitial fluid pressure (IFP), which correlate with increased proliferation and chemosensitivity. In this study, we hypothesized that constitutively raised IFP in OS regulates angiogenesis. Sixteen patients with the clinical diagnosis of OS underwent blood flow and IFP readings by the wick-in-needle method at the time and location of open biopsy. Vascularity was determined by capillary density in the biopsy specimens. We performed digital image analysis of immunohistochemical staining for CD31, VEGF-A, VEGF-C, and TPA on paraffin-embedded tissue blocks of the biopsy samples. Clinical results were validated in a pressurized cell culture system. Interstitial fluid pressures in the tumors (mean 33.5,±,SD 17.2 mmHg) were significantly higher (p,=,0.00001) than that in normal tissue (2.9,±,5.7 mmHg). Pressure readings were significantly higher in low vascularity tumors compared to high vascularity tumors (p,<,0.001). In the OS cell lines, growth in a pressurized environment was associated with VEGF-A downregulation, VEGF-C upregulation, and TPA upregulation. The reverse was seen in the OB cell line. Growth in the HUVEC cell line was not significantly inhibited in a pressurized environment. Immunohistochemical assessment for VEGF-A (p,=,0.01), VEGF-C (p,=,0.008), and TPA (p,=,0.0001) translation were consistent with the findings on PCR. Our data suggests that some molecules in angiogenesis are regulated by changes in IFP. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1520,1525, 2008 [source] Muscle fiber properties and thermal stability of intramuscular connective tissue in porcine M. semimembranosusJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 15 2009Liisa Voutila Abstract BACKGROUND: Strips can be easily peeled from raw destructured pork (M. semimembranosus, SM muscle) by hand but in normal meat these strips break. In general, destructured meat is pale in color. Porcine SM muscles have thick muscle fibers which could predispose them to destructuration. This study investigated whether the onset and peak temperatures of thermal shrinkage (To and Tp) of intramuscular connective tissue from SM muscles were associated with muscle fiber thickness, capillary density or extracellular space. We also investigated whether these muscle fiber properties of destructured muscles differed from those of normal muscles. RESULTS: The destructured and normal muscles were similar in muscle fiber cross-sectional area, capillary density, extracellular space and sarcomere length. To correlated negatively with sarcomere length. The water content of differential scanning calorimetry samples consisting of intramuscular connective tissue was higher in destructured muscles than in normal muscles. CONCLUSION: Muscle fiber properties (muscle fiber cross-sectional area and sarcomere length) and capillary density are similar in destructured and normal SM muscles. To and Tp of intramuscular connective tissue are similar in destructured and normal muscles. Muscle fiber properties show no association with the thermal shrinkage properties of intramuscular connective tissue. Copyright © 2009 Society of Chemical Industry [source] Quantification of Video-Taped Images in Microcirculation Research Using Inexpensive Imaging Software (Adobe Photoshop)MICROCIRCULATION, Issue 2 2000Joachim Brunner ABSTRACT Background: Study end-points in microcirculation research are usually videotaped images rather than numeric computer print-outs. Analysis of these videotaped images for the quantification of microcirculatory parameters usually requires computer-based image analysis systems. Most software programs for image analysis are custom-made, expensive, and limited in their applicability to selected parameters and study end-points. Methods and Result: We demonstrate herein that an inexpensive, commercially available computer software (Adobe Photoshop), run on a Macintosh G3 computer with inbuilt graphic capture board provides versatile, easy to use tools for the quantification of digitized video images. Using images obtained by intravital fluorescence microscopy from the pre- and postischemic muscle microcirculation in the skinfold chamber model in hamsters, Photoshop allows simple and rapid quantification (i) of microvessel diameters, (ii) of the functional capillary density and (iii) of postischemic leakage of FITC-labeled high molecular weight dextran from postcapillary venules. We present evidence of the technical accuracy of the software tools and of a high degree of interobserver reliability. Conclusions: Inexpensive commercially available imaging programs (i.e., Adobe Photoshop) provide versatile tools for image analysis with a wide range of potential applications in microcirculation research. [source] Quantitative measurement of muscle fiber composition in a normal populationMUSCLE AND NERVE, Issue 1 2003Ingrid Toft MD Abstract To obtain normative muscle morphology data on a healthy population recruited from a population survey, we examined vastus lateralis biopsies from 58 men and 33 women, aged 26,67 years. Biopsies were measured with automated, computer-aided techniques. Data were analyzed according to gender and age, and the influence of blood pressure, body mass index (BMI), and smoking habits was also examined. Men had larger muscle fibers (fiber area ,5,400 ,m2) than women (,4,000 ,m2, P = 0.003). No gender differences were seen in fiber composition, fiber roundness, percentage of connective tissue, or capillary density. Blood pressure did not influence fiber size or composition, but was correlated with fiber roundness in men. BMI was associated with fiber area in men, but not in women. Variations in age, smoking habits, and physical activity did not influence muscle morphology data substantially. Thus, in a normal population, men have larger muscle fibers than women, but similar fiber composition. Variation in gender, BMI, blood pressure, and physical activity may influence morphological features to a minor degree. Muscle Nerve 28: 101,108, 2003 [source] Angiogenesis in the Caprine Caruncles in Non-Pregnant and Pregnant Normal and Swainsonine-Treated DoesTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2007S.A. Hafez Abstract Microvascular corrosion casts of caruncles from non-pregnant and pregnant doe goats at 4, 7, 10, 13, 16, and 18 weeks were examined with scanning electron microscopy. The internal convex surface of the caruncles of non-pregnant does was covered with capillary meshes of regular diameter and form, without crypts. As pregnancy advanced the complexity of the vasculature increased: at 4 weeks the surface showed a pattern of ridges separated by troughs. At later stages, branches of radial arteries penetrated the periphery forming an extensive mesh of capillaries on the concave surface. Capillary diameters increased significantly during pregnancy, especially after 4 weeks, when large flattened sinusoids formed. These sinusoids had a great deal of surface area for potential contact with the fetal component. The caprine placenta is usually considered to have increased interhemal distance compared with endotheliochorial and hemochorial types: our results suggest that the very extensive development of sinusoids and crypts may compensate for any negative consequences of the placental architecture. Placental angiogenesis, which is physiologically normal, may serve as a general model of this process in other circumstances, such as tumor. The effect of swainsonine (active compound of locoweed and a potential anticancer drug) on vascular development showed no differences in sinusoidal diameters at 7 weeks, but a decrease in capillary density was noted. Swainsonine caused a great distortion to the vasculature at 18 weeks. The effects of this compound on the vascular development lend credibility to its potential as an anticancer agent. Anat Rec, 2007. © 2007 Wiley-Liss, Inc. [source] Critical overexpression of thrombospondin 1 in chronic leg ischaemiaTHE JOURNAL OF PATHOLOGY, Issue 3 2005Judith Favier Abstract The aim of this study was to identify gene expression governing the balance of angiogenic and angiostatic factors in human ischaemic leg tissues. In situ hybridization was used to screen for the expression of angiogenesis-related genes in tissues from 13 amputated limbs from patients suffering from critical leg ischaemia. The authors tested for mRNA of hypoxia-inducible transcription factors 1, and 2,, vascular endothelial growth factor, and its receptors VEGFR-1 and -2, the angiopoietin receptor Tie2, and the anti-angiogenic molecule thrombospondin 1. The expression levels of the genes in proximal, healthy muscles were compared with those in the distal, ischaemic counterparts. Surprisingly, only thrombospondin 1 was overexpressed in the ischaemic part of the leg of all patients studied. Thrombospondin 1 mRNA was assayed by real-time RT-PCR and the gene was overexpressed 20-fold. The presence of its encoded protein was confirmed by western blotting. The overproduction of this anti-angiogenic molecule was associated with a decrease in capillary density in the affected muscles. Thrombospondin 1 is thus a marker of chronic ischaemia and may affect angiogenesis in ischaemic tissues. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Angiogenesis and Interstitial Pressure in a Rat Tumour ModelANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005H. Hünigen Introduction and Aim:, Angiogenesis, the formation of new blood vessels, is a crucial process in physiological and pathological growth. Pathological angiogenesis is responsible for growth and metastasis of solid tumours, and, when blocked, improves prognosis. As a result of the angiogenic cascade in solid tumours an irregular, leaky capillary network develops. The aim of the present study was to define malignant tumours' vascular characteristics and reveal functional anatomy by quantification of the microvasculature and interstitial pressure (IP) in relation to tumour fluid dynamics as visualized by contrast enhanced magnetic resonance imaging (MRI). Material and Methods:, Dynamic MRI and measurement of the IP was performed in 21 rats implanted with colon carcinomas subcutaneously. Angiogenesis was studied by morphometry of the capillaries, and immunolocalization of the angiogenic factor VEGF and VEGF-Receptor 2. Results and Conclusions:, Histology, immunohistochemistry and MRI confirmed concentric arrangement of 4 tumour zones. The tumour margin included loose connective tissue with abundant mononuclear cells. Many large microvessels were seen in this most intensely vascularized zone. IP measurement in this zone was adjusted to the zero level. Diameter of the peripheral zone of vital cells measured 1.3 mm. Capillaries were smaller and sparse. Dynamic MRI revealed peripheral washout of the contrast agent in this zone. After an initial increase of the signal intensity a hypo-intense rim was formed within a few minutes. The intermediate region was characterized by islands of vital tumour cells containing 3% capillaries (hot spots). The innermost area, the necrotic zone, took 35% of the total tumour area with less than 0.5% vessels. The IP increased from the periphery to the centre. VEGF and VEGF-receptor 2 was found in the vessels of the tumour margin and vital tumour cells of the peripheral zone. From this can be concluded that the peripheral washout phenomenon seems to be correlated with elevated interstitial pressure and increased capillary density and therefore may be a reliable sign of malignancy. [source] Polyurethane Scaffolds Seeded With Genetically Engineered Skeletal Myoblasts: A Promising Tool to Regenerate Myocardial FunctionARTIFICIAL ORGANS, Issue 2 2010Britta Blumenthal Abstract In animal models, intramyocardial injection of primary skeletal myoblasts is supposed to promote tissue regeneration and to improve cardiac function after myocardial infarction. The usage of genetically engineered myoblasts overexpressing the paracrine factors involved in tissue repair is believed to enhance these effects. However, cell therapy via injection is always accompanied by a high death rate of the injected cells. Here, we describe the construction of a growth factor-producing myoblast-seeded scaffold to overcome this limitation. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were seeded on polyurethane (PU) scaffolds (Artelon) and transfected with DNA of VEGF-A, HGF, SDF-1, or Akt1 using the lipid-based Metafectene Pro method. Overexpression was verified by ELISA, RT-PCR (VEGF-A, HGF, and SDF-1) and Western blot analysis (Akt1). The seeded scaffolds were transplanted onto damaged myocardium of Lewis rats 2 weeks after myocardial infarction. Six weeks later, their therapeutic potential in vivo was analyzed by measurement of infarction size and capillary density. Primary rat skeletal myoblasts seeded on PU scaffolds were efficiently transfected, achieving transfection rates of 20%. In vitro, we noted a significant increase in expression of VEGF-A, HGF, SDF-1, and Akt1 after transfection. In vivo, transplantation of growth factor-producing myoblast-seeded scaffolds resulted in enhanced angiogenesis (VEGF-A, HGF, and Akt1) or a reduced infarction zone (SDF-1 and Akt1) in the ischemically damaged myocardium. In summary, we constructed a growth factor-producing myoblast-seeded scaffold which combines the beneficial potential of stem cell transplantation with the promising effects of gene-therapeutic approaches. Because this matrix also allows us to circumvent previous cell application drawbacks, it may represent a promising tool for tissue regeneration and the re-establishment of cardiac function after myocardial infarction. [source] Oestrogen Promotes Coronary Angiogenesis even under Normoxic ConditionsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2008Mehdi Nematbakhsh Oestrogen has angiogenic properties under hypoxic condition, and if oestrogen also induces angiogenesis under normoxic condition, it could be used in combination with other angiogenic therapies in the treatment of ischaemic heart disease. In this study, we evaluated the angiogenic effect of high-dose oestrogen treatment in normoxic rat heart tissue. Fifty-two ovariectomized rats were randomized in oestrogen-treated and control groups. 17,-Oestradiol (1 mg/week) and normal saline (1 mg/week) were administered intramuscularly in the treatment and control groups for 2 months. After that, coronary capillary density and coronary vessel permeability were measured. The serum vascular endothelial growth factor (VEGF) level was also measured before and after the treatment. The results indicate that coronary capillary density (number of capillary per square millimetre) and coronary vessel permeability (fluorescence intensity) were significantly higher in the oestrogen-treated group than in the control group (628 ± 26 per mm2 versus 540 ± 26 per mm2; P < 0.05 and 207 ± 10 versus 147 ± 19 per gram tissue; P < 0.05). Oestrogen treatment increased serum VEGF level in the oestrogen-treated group compared to the control group (52 ± 3 versus 33 ± 6 pg/ml; P < 0.05), but interestingly VEGF was also increased in the control group after placebo treatment. It seems that high-dose oestrogen administration has angiogenic properties even in normoxic conditions. These angiogenic properties may result from oestrogen's direct effect on VEGF or other mechanisms, such as endothelial progenitor cell mobilization. Because of the broad effect of oestrogen on angiogenic growth factors and endothelial cells, more studies are required to clarify angiogenic properties of high-dose oestrogen. [source] Local heat-shock priming-induced improvement in microvascular perfusion in osteomyocutaneous flaps is mediated by heat-shock protein 32BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2001Dr M. Rücker Background: Stress conditioning is thought to improve microvascular free flap survival but the mechanisms of protection are not clear. The aim of this study was to determine whether local induction of heat-shock protein (HSP) 32 improves microvascular perfusion in transferred osteomyocutaneous flaps. Methods: The hindlimb harvest region of osteomyocutaneous flaps in Wistar rats was subjected to stress conditioning by local heating (30 min, 42·5°C) 24 h before microvascular flap transfer. In a second group of animals, after heat-shock priming, the action of HSP-32 was inhibited by tin protoporphyrin IX. Animals with unconditioned flaps served as controls. After transfer, the microcirculation of the muscle, cutaneous, subcutaneous and periosteal tissue of the flap was analysed quantitatively for 6 h using intravital fluorescence microscopy. Results: Immunohistochemistry revealed that HSP-32 was detectable only after priming and not in unconditioned flaps. Priming did not alter functional capillary density or capillary red blood cell velocity compared with that in unconditioned flaps. However, heat-shock priming induced significant capillary dilatation (P < 0·05) and thus a substantial increase in capillary blood flow volume (P < 0·05) in all tissues of the transferred flaps. Inhibition of HSP-32 by tin protoporphyrin IX completely abolished the priming-induced improvement in capillary perfusion, as indicated by the lack of increased capillary diameters and volumetric blood flow. Conclusion: The present study demonstrated that stress conditioning by local heat-shock priming improves nutritive perfusion in osteomyocutaneous flaps by capillary dilatation, probably mediated through the vasoactive action of HSP-32. © 2001 British Journal of Surgery Society Ltd [source] Growth hormone, acromegaly, and heart failure: an intricate triangulationCLINICAL ENDOCRINOLOGY, Issue 6 2003Luigi Saccà Summary Short-term GH or IGF-I excess provides a model of physiological cardiac growth associated with functional advantage. The physiological nature of cardiac growth is accounted for by the following: (i) the increment in cardiomyocyte size occurs prevalently at expense of the short axis. This is the basis for the concentric pattern of left ventricular (LV) hypertrophy, with consequent fall in LV wall stress and functional improvement; (ii) cardiomyocyte growth is associated with improved contractility and relaxation, and a favourable energetic setting; (iii) the capillary density of the myocardial tissue is not affected; (iv) there is a balanced growth of cardiomyocytes and nonmyocyte elements, which accounts for the lack of interstitial fibrosis; (v) myocardial energetics and mechanics are not perturbed; and (vi) the growth response is not associated with the gene re-programming that characterizes pathologic cardiac hypertrophy and heart failure. Overall, the mechanisms activated by GH or IGF-I appear to be entirely different from those of chronic heart failure. Not to be neglected is also the fact that GH, through its nitric oxide (NO)-releasing action, contributes to the maintenance of normal vascular reactivity and peripheral vascular resistance. This particular kind of interaction of GH with the cardiovascular system accounts for: (i) the lack of cardiac impairment in short-term acromegaly; (ii) the beneficial effects of GH and IGF-I in various models of heart failure; (iii) the protective effect of GH and IGF-I against post-infarction ventricular remodelling; (iv) the reversal of endothelial dysfunction in patients with heart failure treated with GH; and (v) the cardiac abnormalities associated with GH deficiency and their correction after GH therapy. If it is clear that GH and IGF-I exert favourable effects on the heart in the short term, it is equally undeniable that GH excess with time causes pathologic cardiac hypertrophy and, if it is not corrected, eventually leads to cardiac failure. Why then, at one point in time in the natural history of acromegaly, does physiological cardiac growth become maladaptive and translate into heart failure? Before this transition takes places, the acromegalic heart shares very few features with other models of chronic heart failure. None of the mechanisms involved in the progression of heart failure is clearly operative in acromegaly, save for the presence of insulin-resistance and mild alterations of lipoproteins and clot factors. Is this enough to account for the development of heart failure? Probably not. On the other hand, it must be stressed that GH and IGF-I activate several mechanisms that play a protective role against the development of heart failure. These include ventricular unloading, deactivation of neurohormonal components, antiapoptotic effect and enhanced vascular reactivity. Ultimately, all data available concur to hypothesize that acromegalic cardiomyopathy represents a progressive model of cardiac hypertrophy in which the cardiotoxic and pro-remodelling effect is intrinsic to the excessive and unrestrained myocardial growth. [source] | |||||||||||||