Correlation of endoanal sonography with cross-sectional anatomy of the anal sphincter

Abstract Background: Anal endosonography has become an important imaging method in the diagnosis of anorectal disorders. However, little information exists as to whether anal endosonography reliably defines pelvic floor structures. The aim of this study was to correlate endoanal sonography with cross-sectional anatomy and histology. Methods: Endosonographic tomograms were obtained from 9 human cadavers before fixation and cross-sectioning at identical levels. Muscular layers were defined by visual inspection, histology, immunohistology, and morphometry using three-dimensional sphincter reconstructions. Results: Endosonography visualized only two muscular layers, whereas anatomic sections al…

Micromechanical forces regulate vascular patterning in the chick chorioallantoic membrane (15.3)

Glycoconjugate expression in the extracellular matrix of the mouse lung (87.7)

Morphology of the dorsal and lateral calcaneocuboid ligaments.

Background: The dorsolateral calcaneocuboid ligaments have different configurations. In the literature they are only described as either the dorsal or lateral calcaneocuboid ligament. However, recent reconstructive surgical techniques may benefit from a better understanding of the anatomy. The aims of this study were to classify the morphology and attachments of the dorso-lateral calcaneocuboid ligaments and to determine their dimensions. Materials and Methods: The dorso-lateral aspects of the calcaneocuboid joint of 30 cadaver feet were dissected to expose the associated ligaments. Further, we evaluated possible bony landmarks of the calcaneus that could imply which shape or course the li…

Impact of single-dose application of TGF-β, copper peptide, stanozolol and ascorbic acid in hydrogel on midline laparatomy wound healing in a diabetic mouse model.

Despite numerous advances and improvements in surgical techniques the incidence of incisional hernias after laparotomy remains high. The aim of this study was to investigate possible effects of single application of ascorbic acid, stanozolol, a synthetic anabolic steroid, copper peptide and transforming growth factor-β (TGF-β) on laparotomy wound healing in an incisional wound model in diabetic mice. After diabetes induction with streptozotozin in Balb-c mice, midline laparatomies were carried out. Closure of the linea alba was followed by single-dose application of the agents dissolved in a hydrogel before skin closure. The functional outcome was assessed in terms of maximum tensile streng…

Intussusceptive Remodeling of Vascular Branch Angles in Chemically-Induced Murine Colitis

Intussusceptive angiogenesis is a developmental process linked to both blood vessel replication and remodeling in development. To investigate the prediction that the process of intussusceptive angiogenesis is associated with vessel angle remodeling in adult mice, we systematically evaluated corrosion casts of the mucosal plexus in mice with trinitrobenzesulphonic acid (TNBS)-induced and dextran sodium sulfate (DSS)-induced colitis. The mice demonstrated a significant decrease in vessel angles in both TNBS-induced and DSS-induced colitis within 4 weeks of the onset of colitis (p<.001). Corrosion casts 28–30 days after DSS treatment were studied for a variety of detailed morphometric changes.…

Migration of CD11b+ accessory cells during murine lung regeneration

In many mammalian species, the removal of one lung leads to growth of the remaining lung to near-baseline levels. In studying post-pneumonectomy mice, we used morphometric measures to demonstrate neoalveolarization within 21 days of pneumonectomy. Of note, the detailed histology during this period demonstrated no significant pulmonary inflammation. To identify occult blood-borne cells, we used a parabiotic model (wild-type/GFP) of post-pneumonectomy lung growth. Flow cytometry of post-pneumonectomy lung digests demonstrated a rapid increase in the number of cells expressing the hematopoietic membrane molecule CD11b; 64.5% of the entire GFP(+) population were CD11b(+). Fluorescence microscop…

Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice

Growth factors and/or angiogenic factors are supposed to improve wound healing. The aim of our study was to evaluate the effects of subcutaneous pretreatment with combinatory proangiogenic factors on wound closure, mechan - ical properties, vessel density and morphology. Twenty-eight Balb/c mice were divided equally into two groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg) and P dGF (3.5 µg) was administered subcutaneously 3, 5 and 7 days to 14 mice before full thickness skin punch biopsy wounding, whereas 14 control animals received three injections of 0.2 ml saline solution. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after complete wound closure. Comp…

Priming with proangiogenic growth factors and endothelial progenitor cells improves revascularization in linear diabetic wounds

In the present study, we investigated whether proangiogenic growth factors and endothelial progenitor cells (EPCs) induce favourable effects on cutaneous incisional wound healing in diabetic mice. The proangiogenic effects of human EPCs were initially analyzed using a HUVEC in vitro angiogenesis assay and an in vivo Matrigel assay in nude mice (n=12). For the diabetic wound model, 48 Balb/c mice with streptozotocin (STZ)-induced diabetes were divided randomly into 4 groups (12 mice in each group). Subsequently, 3, 5 and 7 days before a 15-mm full-thickness incisional skin wound was set, group 1 was pre-treated subcutaneously with a mixture of vascular endothelial growth factor (VEGF)/basic …

Effect of unilateral diaphragmatic paralysis on postpneumonectomy lung growth.

Respiratory muscle-associated stretch has been implicated in normal lung development (fetal breathing movements) and postpneumonectomy lung growth. To test the hypothesis that mechanical stretch from diaphragmatic contraction contributes to lung growth, we performed left phrenic nerve transections (PNT) in mice with and without ipsilateral pneumonectomy. PNT was demonstrated by asymmetric costal margin excursion and confirmed at autopsy. In mice with two lungs, PNT was associated with a decrease in ipsilateral lung volume ( P &lt; 0.05) and lung weight ( P &lt; 0.05). After pneumonectomy, PNT was not associated with a change in activity level, measureable hypoxemia, or altered minute venti…

Bridging Mucosal Vessels Associated with Rhythmically Oscillating Blood Flow in Murine Colitis

Oscillatory blood flow in the microcirculation is generally considered to be the result of cardiopulmonary influences or active vasomotion. In this report, we describe rhythmically oscillating blood flow in the bridging vessels of the mouse colon that appeared to be independent of known biological control mechanisms. Corrosion casting and scanning electron microscopy of the mouse colon demonstrated highly branched bridging vessels that connected the submucosal vessels with the mucosal plexus. Because of similar morphometric characteristics (19 +/- 11 microm vs. 28 +/- 16 microm), bridging arterioles and venules were distinguished by tracking fluorescent nanoparticles through the microcircul…

Structural Remodeling of the Post‐pneumonectomy Lung is Characterized by Septal Retraction and Alveolar Duct Dilation

Murine pneumonectomy (PNX) is an established model of adult compensatory lung growth, involving structural remodeling of the peripheral parenchyma. Following left PNX, positron emission tomography and computerized tomography have demonstrated heterogeneous growth patterns within the remaining right lung. To characterize the structural changes associated with these observations, we analyzed histological sections of the right lung between 3 and 22 days after PNX. Within 3 days of PNX, alveolar septae were significantly shorter (p<0.05) in a majority of alveolar ducts, while septal angle remained unchanged. Septal retraction resulted in an apparent dilation of the alveolar duct with a signific…

Regulatory Network Of Angiogenesis Gene Expression During Post-Pneumonectomy Compensatory Growth

Impact of combinatory growth factor application on rabbit Achilles tendon injury with operative versus conservative treatment: A pilot study

Acute Achilles tendon (AT) rupture is a common injury with a comparatively high complication rate. Presently, surgical treatments compete with nonoperative treatment modalities. The aim of this study was to elucidate the possible beneficial effects of short-term combinatory application of growth factors on tendon healing during operative or conservative treatment. In this controlled laboratory study, the left ATs of 40 adult New Zealand White rabbits were transected and either sutured or treated conservatively. Half of the animals from each treatment modality group repetitively received a mixture of VEGF165, bFGF, and rPDGF which was administered peritendineally. The left legs were immobili…

Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

Abstract Background Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. Methods The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular…

Ocular angiogenesis: translating preclinical indications to successful clinical development

Angiogenesis-related ocular diseases such as age-related macular degeneration (AMD) or diabetic retinopathy have a high socioeconomic impact in western countries and are the leading causes of blindness. Conventional treatment modalities for AMD are of limited success. Inhibition of new vessel formation and targeting of pathological vessels seem to be the best choice in AMD. A variety of animal models mimic the relevant aspects of choroidal neovascularisation (CNV) and allow for therapy screening. Preclinical and clinical studies show that a variety of different strategies are very promising. Stategies include inhibition or blocking of vascular endothelial growth factor, a key player in angi…

Elastin Cables Define the Axial Connective Tissue System in the Murine Lung

The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanni…

Mechanostructural adaptations preceding postpneumonectomy lung growth

In many species, pneumonectomy results in compensatory growth in the remaining lung. Although the late mechanical consequences of murine pneumonectomy are known, little is known about the anatomic adaptations and respiratory mechanics during compensatory lung growth. To investigate the structural and mechanical changes during compensatory growth, mice were studied for 21 days after left pneumonectomy using microCT and respiratory system impedance (FlexiVent). Anatomic changes after left pneumonectomy included minimal mediastinal shift or chestwall remodeling, but significant displacement of the heart and cardiac lobe. Mean displacement of the cardiac lobe centroid was 5.2 ± 0.8 mm. Lung imp…

Priming with a Combination of Proangiogenic Growth Factors Enhances Wound Healing in Streptozotocin-Induced Diabetes in Mice

&lt;i&gt;Background:&lt;/i&gt; Numerous proangiogenic growth factors have been shown to improve impaired wound healing. This study evaluated the effects of subcutaneous pretreatment with a combination of proangiogenic growth factors on wound closure, mechanical properties, vessel density, and morphology. &lt;i&gt;Methods:&lt;/i&gt; Thirty-six Balb/c mice with streptozotocin-induced diabetes were divided into 3 groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg), and PDGF (3.5 µg) was administered subcutaneously 3, 5, and 7 days prior to wounding in the first group, whereas the second group received three doses of 3.5 µg PDGF. Wound sizes were assessed daily and the repaired tissues were harv…

Adnectin CT-322 inhibits tumor growth and affects microvascular architecture and function in Colo205 tumor xenografts

Antiangiogenesis has become a promising pillar in modern cancer therapy. This study investigates the antiangiogenic effects of the PEGylated Adnectin™, CT-322, in a murine Colo-205 xenograft tumor model. CT-322 specifically binds to and blocks vascular endothelial growth factor receptor (VEGFR-2). Adnectins are a novel class of targeted biologics engineered from the 10th domain of human fibronectin. CT-322 treated tumors exhibited a significant reduction in tumor growth of 69%, a 2.8 times lower tumor surface area and fewer necrotic areas. Control tumors showed a 2.36-fold higher microvessel density (MVD) and a 2.42 times higher vessel volume in corrosion casts. The vascular architecture in…

Endoscopic transventricular third ventriculostomy through the lamina terminalis

Object Endoscopic third ventriculostomy (ETV) has become a well-accepted option for obstructive hydrocephalus. However, standard ventriculostomy at the floor of the third ventricle might not be feasible under certain conditions. Here, the authors report in detail on their initial experience with an alternative option of endoscopic ventriculostomy through the lamina terminalis via a transventricular route. Methods Endoscopic third ventriculostomy through the lamina terminalis from a transventricular transforaminal route was evaluated in 4 cadaveric human heads and in 4 clinical cases. Results In all 4 human cadavers, an opening of the lamina terminalis via a transventricular approach could …

Forces and deformations of the abdominal wall—A mechanical and geometrical approach to the linea alba

Force-elongation responses of the human abdominal wall in the linea alba region were determined by tensile tests in which the linea alba was seen to exhibit a nonlinear elastic, anisotropic behavior as is frequently observed in soft biological tissues. In addition, the geometry of the abdominal wall was determined, based on MRI data. The geometry can be specified by principal radii of curvature in longitudinal of approximately 470 mm and in the transverse direction of about 200 mm. The determined radii agree with values found in other studies. Mechanical stresses, deformations and abdominal pressures for load cases above 6% elongation can be related using Laplace's formula and our constitut…

Vascular Microarchitecture of Murine Colitis-Associated Lymphoid Angiogenesis

In permissive tissues, such as the gut and synovium, chronic inflammation can result in the ectopic development of anatomic structures that resemble lymph nodes. These inflammation-induced structures, termed lymphoid neogenesis or tertiary lymphoid organs, may reflect differential stromal responsiveness to the process of lymphoid neogenesis. To investigate the structural reorganization of the microcirculation involved in colonic lymphoid neogenesis, we studied a murine model of dextran sodium sulfate (DSS)-induced colitis. Standard 2-dimensional histology demonstrated both submucosal and intramucosal lymphoid structures in DSS-induced colitis. A spatial frequency analysis of serial histolog…

Anatomic and flow dynamic considerations for safe right axillary artery cannulation.

Objectives Neuroprotection is of paramount interest in cardiac surgery. Right axillary artery cannulation is well established in aortic surgery because it significantly improves survival and outcome, but malperfusion of the right brain after direct cannulation has been reported. Anatomically, 4 vessel segments are potentially amenable for cannulation of the subclavian and axillary arteries. Clinical studies vary widely in dissection sites and cannulation techniques. We investigated critical flow dynamics in the right brain caused by arterial inflow after direct cannulation and specified cannulation positions that provide optimal cerebral perfusion. Methods Distances from the lateral margin …

Stimulation of regional lymphatic and blood flow by epicutaneous oxazolone.

The application of the epicutaneous antigen oxazolone results in persistent induration and erythema; however, the relative changes in lymph and blood flow in the inflammatory skin are largely unknown. To define the contribution of lymph and blood flow to the clinical appearance of cutaneous inflammation, we studied the sheep ear after the application of oxazolone. As a model for the study of these changes, the sheep ear had several experimental advantages: 1) a simplified superficial vascular network, 2) defined lymphatic drainage, and 3) an avascular and alymphatic cartilaginous barrier. Lymph flow was continuously monitored by cannulation of the prescapular efferent lymph duct. Blood flo…

Investigation of inhibitory effects on EPC-mediated neovascularization by different bisphosphonates for cancer therapy.

Bisphosphonates (BPs) are potent drugs, used in metastatic cancer-like prostate or breast carcinoma. In recent studies, besides reduced bone remodeling, influences on angiogenesis and neovascularization were reported. Since BPs have the tendency to accumulate in the bones, the biological effect of various nitrogen- and non-nitrogen BPs on endothelial progenitor cells (EPCs) that originated from bone marrow and mobilized under physiological and pathophysiological conditions, such as tumor neovascularization, was investigated. EPCs subsequent to 72-h treatment with different concentrations of bisphosphonates comprised the non-nitrogen-containing BP clodronate and the nitrogen-containing BPs i…

Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization

In most rodents and some other mammals, the removal of one lung results in compensatory growth associated with dramatic angiogenesis and complete restoration of lung capacity. One pivotal mechanism in neoalveolarization is neovascularization, because without angiogenesis new alveoli can not be formed. The aim of this study is to image and analyze three-dimensionally the different patterns of neovascularization seen following pneumonectomy in mice on a sub-micron-scale. C57/BL6 mice underwent a left-sided pneumonectomy. Lungs were harvested at various timepoints after pneumonectomy. Volume analysis by microCT revealed a striking increase of 143 percent in the cardiac lobe 14 days after pneum…

The Vascular Anatomy of the Inner Anterior Abdominal Wall with Special Reference to the Transversus and Rectus Abdominis Musculoperitoneal (TRAMP) Composite Flap for Vaginal Reconstruction

This study was designed to clarify the vascularization of the inner anterior abdominal wall with respect to the novel transversus and rectus abdominis musculoperitoneal (TRAMP) flap, which was introduced recently for vaginal reconstruction. A series of human cadavers was injected with a lead oxide-gelatine mixture by means of the deep inferior epigastric artery and subsequently dissected and examined by radiography. In all cases we found that the blood supply of the entire rectus abdominis muscle from the symphysis to the costal arch and that of the medial 10 to 15 cm of the transversus abdominis muscle, as well as the underlying peritoneum, was provided by several branches of the deep infe…

Abstract B09: Nintedanib inhibits tumor and vessel growth and leads to vascular normalization in A549-NSCLC-xenografts

Abstract Angiogenesis plays a major role in the growth and progression of non-small-cell lung cancer (NSCLC). The triple angiokinase inhibitor nintedanib is a potent inhibitor of the receptor tyrosine kinases FGFR-1, 2, 3, PDGFR-α and β, VEGFR-1, 2, 3. and Flt-3. as well as of non-receptor tyrosine kinases like Src, Lyn and Lck by occupying the intracellular ATP-binding pocket. In the pivotal LUME-Lung 1 trial Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma. The aim of this study was to analyse treatment induced vascular normalization of nintedanib, bevacizumab and docetaxel …

Three-dimensional image analytical detection of intussusceptive pillars in murine lung

A variety of diseases can lead to loss of lung tissue. Currently, this can be treated only symptomatically. In mice, a complete compensatory lung growth within 21 days after resection of the left lung can be observed. Understanding and transferring this concept of compensatory lung growth to humans would greatly improve therapeutic options. Lung growth is always accompanied by a process called angiogenesis forming new capillary blood vessels from preexisting ones. Among the processes during lung growth, the formation of transluminal tissue pillars within the capillary vessels (intussusceptive pillars) is observed. Therefore, pillars can be understood as an indicator for active angiogenesis …

Metalloproteases meprin α and meprin β are C- and N-procollagen proteinases important for collagen assembly and tensile strength.

Type I fibrillar collagen is the most abundant protein in the human body, crucial for the formation and strength of bones, skin, and tendon. Proteolytic enzymes are essential for initiation of the assembly of collagen fibrils by cleaving off the propeptides. We report that Mep1a −/− and Mep1b −/− mice revealed lower amounts of mature collagen I compared with WT mice and exhibited significantly reduced collagen deposition in skin, along with markedly decreased tissue tensile strength. While exploring the mechanism of this phenotype, we found that cleavage of full-length human procollagen I heterotrimers by either meprin α or meprin β led to the generation of mature collagen molecules that s…

A comparison of three different micro-tomography systems for accurate determination of microvascular parameters

The investigation of micro-vessel dimensions in 3D is currently problematic due to their complex structures and fine scale. Quantification of vascular parameters is important in several fields of biomedicine; including embryogenesis, wound healing, diseases characterized by uncontrolled angiogenesis (e.g. tumor growth and metastasis) and the development of implantable bio-materials where a functional vascular supply is critical to their successful integration into host tissue. However, techniques that can resolve the micron-scaled features of these capillary beds, such as scanning electron and confocal microscopy, do not allow for total image reconstitution in 3 D in thick tissue samples [1…

Microangiectasias: Structural regulators of lymphocyte transmigration

The migration of lymphocytes into inflammatory tissue requires the migrating cell to overcome mechanical forces produced by blood flow. A generally accepted hypothesis is that these forces are overcome by a multistep sequence of adhesive interactions between lymphocytes and endothelial cells. This hypothesis has been recently challenged by results demonstrating wall shear stress on the order of 20 dyn/cm 2 in vivo and infrequent lymphocyte–endothelial adhesion at wall shear stress &gt;1–2 dyn/cm 2 in vitro . Here, we show that lymphocyte slowing and transmigration in the skin is associated with microangiectasias, i.e., focal structural dilatations of microvessel segments. Microangiectasias…

Acceleration of image filtering algorithms for 3D visualization of murine lungs using dataflow engines

Image filtering is one of the most common and important tasks in image processing applications. In this paper, image processing using a mean filtering algorithm combined with thresholding and binarization algorithms for the 3D visualization and analysis of murine lungs is explained. These algorithms are then mapped on the Maxler's MAX2336B Dataflow Engine (DFE) to significantly increase calculation speed. Several different DFE configurations were tested and each yielded different performance characteristics. Optimal algorithm calculation speed was up to 30 fold baseline calculation speed.

Vessel painting of the microcirculation using fluorescent lipophilic tracers

Flexible approaches to defining microvessel morphometry are useful in the study of both acute and chronic structural changes of the microcirculation. In this report, we examined the utility of the intravascular infusion of lipophilic carbocyanine tracers in the structural assessment of the retina, skin, lung, and colon microcirculation. The microvessel labeling technique, here termed fluorescent vessel painting, involved the intravascular injection of sulfonated lipophilic carbocyanine tracers. The utility of vessel painting in morphometry was assessed using morphometric comparisons with corrosion casting and 2-dimensional and 3-dimensional scanning electron microscopy. The comparisons demo…

The murine bronchopulmonary microcirculation in hapten-induced inflammation

ObjectiveThe clinical observation of central bronchial artery hypertrophy in chronic lung inflammation suggests the possibility that the bronchial circulation may also participate in adaptive responses in peripheral lung inflammation.MethodsTo investigate the potential role of the bronchial microcirculation in peripheral lung inflammation, we developed a murine model of lung inflammation using the intratracheal instillation of the peptide-hapten trinitrophenol in presensitized mice.ResultsClinical parameters indicated a peak inflammatory response at 96 hours. Similarly, gross and microscopic evidence of inflammation was observed 96 hours after antigen instillation. Using a forced oscillatio…

Freezing without surrounding cryomedium preserves the endothelium and its function in human internal mammary arteries

Abstract Purpose Cryopreserved human blood vessels may become important tools in bypass surgery. Optimal cryopreservation of an arterial graft should, therefore, preserve both histological and physiological characteristics of smooth muscle and endothelium comparable to the unfrozen artery. Methods Rings from human internal mammary arteries (IMA) were investigated in vitro either unfrozen or after immersion into a cryomedium (RPMI 1640 containing 1.8 M Me2SO and 0.1 M sucrose) and cryostorage with and without surrounding medium. Results In unfrozen IMA, neither contractile responses to noradrenaline (NA) nor endothelium-dependent relaxant responses to acetylcholine (ACH) was modified after e…

Computational flow dynamics in a geometric model of intussusceptive angiogenesis.

Intussusceptive angiogenesis is a process that forms new blood vessels by the intraluminal division of a single blood vessel into two lumens. Referred to as nonsprouting or intussusceptive angiogenesis, this angiogenic process has been described in morphogenesis and chronic inflammation. Mechanical forces are relevant to the structural changes associated with intussusceptive angiogenesis because of the growing evidence that physiologic forces influence gene transcription. To provide a detailed analysis of the spatial distribution of physiologic shear stresses, we developed a 3D finite element model of the intraluminal intussusceptive pillar. Based on geometries observed in adult intussuscep…

Alveolar Epithelial Dynamics in Postpneumonectomy Lung Growth

The intimate anatomic and functional relationship between epithelial cells and endothelial cells within the alveolus suggests the likelihood of a coordinated response during postpneumonectomy lung growth. To define the population dynamics and potential contribution of alveolar epithelial cells to alveolar angiogenesis, we studied alveolar Type II and I cells during the 21 days after pneumonectomy. Alveolar Type II cells were defined and isolated by flow cytometry using a CD45(-) , MHC class II(+) , phosphine(+) phenotype. These phenotypically defined alveolar Type II cells demonstrated an increase in cell number after pneumonectomy; the increase in cell number preceded the increase in Type …

Alveolar macrophage dynamics in murine lung regeneration

In most mammalian species, the removal of one lung results in dramatic compensatory growth of the remaining lung. To investigate the contribution of alveolar macrophages (AMs) to murine post-pneumonectomy lung growth, we studied bronchoalveolar lavage (BAL)-derived AM on 3, 7, 14 and 21 days after left pneumonectomy. BAL demonstrated a 3.0-fold increase in AM (CD45(+), CD11b(-), CD11c(+), F4/80(+), Gr-1(-)) by 14 days after pneumonectomy. Cell cycle flow cytometry of the BAL-derived cells demonstrated an increase in S + G2 phase cells on days 3 (11.3 ± 2.7%) and 7 (12.1 ± 1.8%) after pneumonectomy. Correspondingly, AM demonstrated increased expression of VEGFR1 and MHC class II between days…

Pulmonary Mechanics Suggest Mechanical Forces Trigger Neoalveolarization In A Murine Model Of Compensatory Lung Growth

QS159. Structural Adaptations Increase Mucosal Capillary Density in Prolonged Murine Colitis

Improved Regeneration of Autologous Nerve Transplants by Means of VEGF-Gene Therapy

The impact of the Vascular Endothelial Growth Factor (VEGF) on the angiogenic cascade is proven. Recently its neuroprotective effect after peripheral nerve injuries on α-motoneurons in the spinal cord was shown. Experiments on α-motoneurons demonstrated a decreased sensitivity to ischemia under VEGF-therapy. Aim of the study was to elucidate the effect of a localized VEGF-gene-therapy using an adenoviral vector construct in the model of a peripheral nerve defect in the rat treated with an autologous nerve transplant.

Biomechanical and histological evaluation of abdominal wall compliance with intraperitoneal onlay mesh implants in rabbits: A comparison of six different state-of-the-art meshes

Abstract Background An ideal prosthetic mesh for incisional hernia repair should mimic the anisotropic compliance of the abdominal wall, and at lower loads should exhibit higher distensibility without impairment of safety at higher loads. This study evaluated the biomechanical properties of six meshes in a rabbit model. Methods New Zealand white rabbits were used for this study. Two meshes of the same brand (Ethicon Physiomesh™, Bard Composix ® L/P, Gore Dualmesh ® , Bard Sepramesh ® , Ethicon Proceed ® or Parietex™ Composite) were implanted into each animal for assessment of intra-abdominal hernia repair, with a total of ten meshes per group. Twelve weeks after implantation, the abdominal …

Inflammation-Induced Intussusceptive Angiogenesis in Murine Colitis

Intussusceptive angiogenesis is a morphogenetic process that forms new blood vessels by the division of a single blood vessel into two lumens. Here, we show that this process of intraluminal division participates in the inflammation-induced neovascularization associated with chemically induced murine colitis. In studies of both acute (4-7 days) and chronic (28-31 days) colitis, intravital microscopy of intravascular tracers demonstrated a twofold reduction in blood flow velocity. In the acute colitis model, the decreased velocity was associated with marked dilatation of the mucosal plexus. In contrast, chronic inflammation was associated with normal caliber vessels and duplication (and trip…

Dynamic deformation of migratory efferent lymph-derived cells ?trapped? in the inflammatory microcirculation

The cellular immune response depends on the delivery of lymphocytes from the lymph node to the peripheral site of antigenic challenge. During their passage through the inflammatory microcirculaton, the migratory cells can become transiently immobilized or "trapped" in small caliber vessels. In this report, we used intravital microscopy and temporal area mapping to define the dynamic deformation of efferent lymph-derived mononuclear cells trapped in the systemic inflammatory microcirculation. Mononuclear cells obtained from the efferent lymph draining the oxazolone-stimulated microcirculation were labeled with fluorescent dye and reinjected into the feeding arterial circulation. Intravital v…

Mapping cyclic stretch in the postpneumonectomy murine lung

In many mammalian species, the removal of one lung [pneumonectomy (PNX)] is associated with the compensatory growth of the remaining lung. To investigate the hypothesis that parenchymal deformation may trigger lung regeneration, we used respiratory-gated micro-computed tomography scanning to create three-dimensional finite-element geometric models of the murine cardiac lobe with cyclic breathing. Models were constructed of respiratory-gated micro-computed tomography scans pre-PNX and 24 h post-PNX. The computational models demonstrated that the maximum stretch ratio map was patchy and heterogeneous, particularly in subpleural, juxta-diaphragmatic, and cephalad regions of the lobe. In these…

Non-viral VEGF(165) gene therapy--magnetofection of acoustically active magnetic lipospheres ('magnetobubbles') increases tissue survival in an oversized skin flap model.

Abstract Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF165-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound. We prepared perfluoropropane-filled magnetic lipospheres (‘magnetobubbles’) from Tween60-coated magnetic nanoparticles, Metafectene, soybean-oil and cDNA and studied the effect in an oversized random-pattern-flap model in the rats (n= 46). VEGF-cDNA-magnetobubbles were administered under a magnetic field with simultaneousl…

Angiogenesis in Wounds Treated by Microdeformational Wound Therapy.

BACKGROUND:: Mechanical forces play an important role in tissue neovascularization and are a constituent part of modern wound therapies. The mechanisms by which vacuum assisted closure (VAC) modulates wound angiogenesis are still largely unknown. OBJECTIVE:: To investigate how VAC treatment affects wound hypoxia and related profiles of angiogenic factors as well as to identify the anatomical characteristics of the resultant, newly formed vessels. METHODS:: Wound neovascularization was evaluated by morphometric analysis of CD31-stained wound cross-sections as well as by corrosion casting analysis. Wound hypoxia and mRNA expression of HIF-1α and associated angiogenic factors were evaluated by…

Three-dimensional analysis of tumour vascular corrosion casts using stereoimaging and micro-computed tomography

Objective: In order to perform effective translational research for cancer therapy, we need to employ preclinical models which reflect the clinical situation. The purpose of this study was to quantitatively compare the vascular architecture of human colorectal cancer and experimental tumour models to determine the suitability of animal models for vascular studies and antivascular therapy.Methods: In this study we investigated the three-dimensional properties of colonic tumour vasculature in both human clinical tissues (normal mucosa control [n = 20], carcinoma [n = 20] and adenoma In = 61) and murine colorectal xenografts (LS147T [n = 6] and SW1222 [n = 6]). Scanning Electron Microscope Ste…

Dendritic Cell Migration To The Post Pneumonectomy Lung

Bimodal Oscillation Frequencies of Blood Flow in the Inflammatory Colon Microcirculation

Rhythmic changes in blood flow direction have been described in the mucosal plexus of mice with acute colitis. In this report, we studied mice with acute colitis induced either by dextran sodium sulfate or by trinitrobenzenesulfonic acid. Both forms of colitis were associated with blood flow oscillations as documented by fluorescence intravital videomicroscopy. The complex oscillation patterns suggested more than one mechanism for these changes in blood flow. By tracking fluorescent nanoparticles in the inflamed mucosal plexus, we identified two forms of blood flow oscillations within the inflammatory mouse colon. Stable oscillations were associated with a base frequency of approximately 2 …

Laser Microdissection of the Alveolar Duct Enables Single-Cell Genomic Analysis

Complex tissues such as the lung are composed of structural hierarchies such as alveoli, alveolar ducts, and lobules. Some structural units, such as the alveolar duct, appear to participate in tissue repair as well as the development of bronchioalveolar carcinoma. Here, we demonstrate an approach to conduct laser microdissection of the lung alveolar duct for single-cell PCR analysis. Our approach involved three steps. The initial preparation used mechanical sectioning of the lung tissue with sufficient thickness to encompass the structure of interest. In the case of the alveolar duct, the precision-cut lung slices were 200µm thick; the slices were processed using near-physiologic conditions…

Selective Laser Photocoagulation Manipulates Blood Flow Dynamics in Microcirculation

Sequence of vascular patterning and gene transcription in the chick chorioallantoic membrane (15.1)

Introduction: The chick chorioallantoic membrane (CAM) is a well-established model of both vasculogenesis and angiogenesis; however, little is known about the genetic control of vascular patterning in the CAM. Methods: Using recent advances in chicken genomics, we investigated the relative expression of 84 angiogenesis genes during the growth and remodeling of the CAM microcirculatory network. Chick embryos, cultured ex ovo, were studied during embryonic development days (EDD) 8-14. UV laser microdissection was used to harvest capillary plexus and 1st, 2nd, and 3rd order conducting vessels for qRT-PCR analysis. Results: Two transcription peaks were observed between EDD 8 and 14. The first p…

Inflammation-responsive focal constrictors in the mouse ear microcirculation

In many capillary exchange beds, blood flow is locally regulated by precapillary sphincter-like activity. In this study, we used intravascular tracers and scanning electron microscopy to investigate precapillary blood flow regulation in the mouse ear. Gelatin ink injections of the normal mouse ear demonstrated 6.8 +/- 2.3 axial vessels with a cutoff of detectable tracer in the early branches: 19 +/- 11 focal constrictions were observed along the 1st to 5th order branches of the axial vessels. A perfusion tracer consisting of biotinylated anti-endothelial lectins (Ricinus Communis Agglutin, Lycopersicon Esculentum and Griffonia Simplicifolia) was circulated for 30 min under physiological con…

Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A188 from the αA-crystallin promoter

Purpose During growth of the embryonic eye, dose- and site-specific expression of heparin-binding growth factors is critical for the formation of an appropriate vascular supply. Overexpression of vascular endothelial growth factor-A188 (VEGF-A188), a strongly heparin-binding, endothelial-specific mitogen, leads to severe disturbance of vascular and overall ocular morphology. This study aimed to evaluate the effects of VEGF-A188 overexpression on growth of ocular tissue components. Methods Stereological and immunohistochemical methods were employed to identify the vascular profiles, ocular tissue proportions, and cell types in VEGF-A188 transgenic mice and compare them with wild-type mice. R…

Focal topographic changes in inflammatory microcirculation associated with lymphocyte slowing and transmigration

Microcirculation is the primary mechanism for delivering lymphocytes to inflammatory tissues. Blood flow within microvessels ensures a supply of lymphocytes at the blood-endothelial interface. Whether the structure of the inflammatory microcirculation facilitates lymphocyte transmigration is less clear. To illuminate the microcirculatory changes associated with lymphocyte transmigration, we used intravital videomicroscopy to examine the dermal microcirculation after application of the epicutaneous antigen oxazolone. Intravascular injection of fluorescein-labeled dextran demonstrated focal topographic changes in the microcirculation. These focal changes had the appearance of loops or hairpin…

Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells.

Proteolysis mediated by the ubiquitin-proteasome system has been implicated in the regulation of programmed cell death. Here we investigated the differential effects of proteasomal inhibitors on the viability of proliferating and quiescent primary endothelial cells in vitro and in vivo. Subconfluent, proliferating cells underwent carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI) -induced apoptosis at low concentrations (EC(50)=24 nM), whereas at least 340-fold higher concentrations of PSI were necessary to obtain the same effect in confluent, contact-inhibited cells. PSI-mediated cell death could be blocked by a caspase-3 inhibitor (Ac-DEVD-H), but not by a caspase…

Post‐pneumonectomy Lung Deformation is Associated with Alveolar Type II Cell Apoptosis and Altered Parenchymal Mechanics

Periosteal repair of the dorsal calcaneocuboid ligament: a comparative biomechanical study.

Background: Isolated lateral calcaneocuboid joint instability rarely is described. Missed or delayed diagnosis resulting in inadequate treatment may lead to chronic instability, followed by sports inability and handicap in daily life. Besides arthrodesis, anatomic repair augmenting the elongated dorsal calcaneocuboid ligament with a local periosteal flap has recently been described for treatment. Methods: In a controlled laboratory study, eight isolated fresh-frozen human cadaver calcaneocuboid specimens were strained in a varus direction until failure of the dorsal calcaneocuboid ligaments. Then the dorsal calcaneocuboid ligaments were reconstructed with free periosteal flaps and tensile …

Blood flow patterns spatially associated with platelet aggregates in murine colitis.

In the normal murine mucosal plexus, blood flow is generally smooth and continuous. In inflammatory conditions, such as chemically-induced murine colitis, the mucosal plexus demonstrates markedly abnormal flow patterns. The inflamed mucosal plexus is associated with widely variable blood flow velocity as well as discontinuous and even bidirectional flow. To investigate the mechanisms responsible for these blood flow patterns, we used intravital microscopic examination of blood flow within the murine mucosal plexus during dextran sodium sulphate-and trinitrobenzenesulfonic acid-induced colitis. The blood flow patterns within the mucosal plexus demonstrated flow exclusion in 18% of the vessel…

Murine Microvideo Endoscopy of the Colonic Microcirculation

Natural orifice endoscopy in small animal models has been limited in the past by instrument size and optical performance. In this report, we investigate the feasibility of using a recently developed microvideo endoscopy system to evaluate the colon microcirculation. Using a murine model of acute colitis, microvideo endoscopy was useful in mapping the topography of inflammation as well as identifying relevant structures in the microcirculation. We conclude that natural orifice endoscopy is a useful method for the minimally invasive longitudinal assessment of the colonic mucosal microcirculation.

Magnetofection of acoustically active „magnetic microspheres“ (Magnetobubbles) — Induction of angiogenesis via non-viral transfection of VEGF

Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study we investigated the potential of magnetofection of magnetic lipospheres containing VEGF165-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound.

Architectural changes of the extracellular matrix in compensatory lung growth (540.2)

Compensatory growth of the remaining lung after murine pneumonectomy (PNX) involves the structural remodeling of the peripheral acini. Although the role of stem cells and local cellular proliferati...

Finger injuries caused by power-operated windows of motor vehicles: an experimental cadaver study.

The aim of this experimental cadaver study was to investigate which kinds of lesions could occur in jam events between the glass and seal entry of power-operated motor vehicle side door windows at two different closing forces. Ten hands of fresh cadaver specimens were used. Three different hand positions chosen to simulate real events in which a finger is jammed between the glass and seal entry of the window of a current motor vehicle were examined. The index, middle, ring, and little finger of each hand were separately jammed both at the proximal and distal interphalangeal joint at closing forces of 300 and 500 N with a constant window glass closing speed of 10 cm/s. Macroscopically visibl…

Chirurgische Anatomie und neurophysiologische Parameter zur intraoperativen Identifikation und Funktionsprüfung autonomer Beckennerven bei TME wegen Rektumkarzinom

Introduction The identification and preservation of parasympathetic and sympathetic pelvic nerves is required to avoid urogenital malfunctions after TME for rectal carcinoma. The objective was to determine the surgical topography of the nerves with regard to TME. Neurophysiologiecl parameters for the intraoperative stimulation of the detrusor muscle were assessed in order to establish a functional test for the intraoperative identification of the pelvic autonomic nerves.

Möglichkeiten und Grenzen der Mikrogefäßdarstellung

Vessel systems and the microvascular unit may be studied by a variety of morphological techniques which enable improved structure-function analyses. Two-dimensional light and electron microscopic sectioning techniques with and without specific markers are complemented by 3D vascularisation and perfusion study techniques. Static ex vivo modalities still prevail, however, the future will be dominated by intravital high-resolution techniques.

Regulation Of Post-Pneumonectomy Angiogenesis By Type II Pneumocytes

Vascular Endothelial Growth Factor Gene Therapy Promotes Nerve Regeneration in a Sciatic Nerve Graft Model in Rats

: Incomplete nerve regeneration after injuries to the peripheral nervous system remains a significant problem in clinical routine and raises the need for supportive strategies. In this study we examined the effect of VEGF-gene therapy on nerve recovery after an auto-graft implantation in a 2 cm sciatic nerve defect model in 18 rats, using an adenoviral vector encoding for VEGF165 (AdCMV.VEGF 165 ) for gene transduction. Functional recovery was assessed weekly by gait analyses of the rats’ hind limbs. Morphometric evaluation including histology, axon counts, motor neuron counts and corrosion casting was carried out 18 weeks post-op. VEGF-treated animals contained a higher proportion of large…

Remodeling of alveolar septa after murine pneumonectomy

In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) ( P &gt…

AdVEGF165gene transfer increases survival in overdimensioned skin flaps

Background Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. VEGF A also plays an important role in wound healing of the skin by promoting angiogenesis and by stimulating blood vessel growth. Therefore we tested the hypothesis that flap survival could be increased by the preoperative injection of AdVEGF165. Methods We studied the effect of AdVEGF165 in an overdimensioned ischemic random-pattern-flap model in the rat (n = 50) with a length-to-width ratio of 4 : 1. VEGF cDNA was administered in two concentrations of 5 × 108 plaque-forming units (pfU) and 1 × 109 pfU using a recombinant adenoviral vector. Recombinant virus was injected subdermally 7, 3 or 0 days pri…

QS280. Mesoscopic Traffic Flow Theory Characterizes Microhemodynamics in Chemically-Induced Murine Colitis

Submicron Scale-Structured Hydrophilic Titanium Surfaces Promote Early Osteogenic Gene Response for Cell Adhesion and Cell Differentiation

cid_339 166..175 ABSTRACT Background and Purpose: Titanium (Ti) surface roughness and surface hydrophilicity are key factors to regulate osteogenic cell responses during dental implant healing. In detail, specific integrin-mediated interactions with the extracellular environment trigger relevant osteogenic cell responses like differentiation and matrix synthesis via transcriptions factors. Aim of this study was to monitor surface-dependent osteogenic cell adhesion dynamics, proliferation, and specific osteo- genic cell differentiation over a period of 7 days. Materials and Methods: Ti disks were manufactured to present smooth pretreatment (PT) surfaces and rough sandblasted/ acid-etched (SL…

Aortenklappenstrukturen als Orientierungshilfe zum Auffinden der Koronararterienabgänge in der transthorakalen Echokardiographie

Die Koronararterienabgange werden gelegentlich bei der echokardiographischen Untersuchung mit erfasst. Es fragte sich, ob diese Modalitat als nicht invasive Screeninguntersuchung genutzt werden kann. Voraussetzung hierfur ist eine sichere und reproduzierbare Erfassung der Koronararterienabgange. Patienten und Methode: Vor diesem Hintergrund wurde an 20 anatomischen Praparaten morphometrisch und an 50 Patienten einer kardiologischen Praxis mit transthorakalem Ultraschall die Abgangstopographie ausgemessen. Ergebnisse: Die Koronarostien lagen konstant exzentrisch im Sinus in Richtung des akoronaren Sinus verschoben. Der Abstand des linken Koronararterienostiums von der Kommissur zwischen Valv…

Stretch-induced Intussuceptive and Sprouting Angiogenesis in the Chick Chorioallantoic Membrane

Vascular systems grow and remodel in response to not only metabolic needs, but also mechanical influences as well. Here, we investigated the influence of tissue-level mechanical forces on the patterning and structure of the chick chorioallantoic membrane (CAM) microcirculation. A dipole stretch field was applied to the CAM using custom computer-controlled servomotors. The topography of the stretch field was mapped using finite element models. After 3 days of stretch, Sholl analysis of the CAM demonstrated a 7-fold increase in conducting vessel intersections within the stretch field (p 0.05). In contrast, corrosion casting and SEM of the stretch field capillary meshwork demonstrated intense …

Spatial calibration of structured illumination fluorescence microscopy using capillary tissue phantoms.

Quantitative assessment of microvascular structure is relevant to the investigations of ischemic injury, reparative angiogenesis and tumor revascularization. In light microscopy applications, thick tissue specimens are necessary to characterize microvascular networks; however, thick tissue leads to image distortions due to out-of-focus light. Structured illumination confocal microscopy is an optical sectioning technique that improves contrast and resolution by using a grid pattern to identify the plane-of-focus within the specimen. Because structured illumination can be applied to wide-field (nonscanning) microscopes, the microcirculation can be studied by sequential intravital and confocal…

Maximum forces acting on the abdominal wall: Experimental validation of a theoretical modeling in a human cadaver study

Incisional hernias following median laparotomy have a high incidence and recurrence rate after repair, so that a better understanding of the linea alba biomechanics is desirable. The mechanical stress exerted on the linea alba in living humans is primarily generated by the musculature. In this human cadaver study, intraabdominal pressure was simulated by insertion of a balloon that was increasingly filled to maximal pressures of 200 mbar. The related forces acting transversely on the linea alba at maximum pressure were found to be between 41.6 and 52.2 N/cm (mean = 45.9 N/cm), which is in agreement with a recent modeling of the related forces.

Innervation der subperitonealen Beckenetage: Möglichkeiten zur Optimierung der Rektumchirurgie

Einleitung: Bei totaler mesorektaler Exzision (TME) soll die Rate postoperativer urogenitaler Funktionsstorungen durch genauere topographische Kenntnisse von Faszien- und Nervenverlaufen weiter abgesenkt werden. Methodik: An 10 anatomischen Korperspenden wurden makroskopische Praparationen, schnittanatomische Studien, histologische und immunhistochemische Untersuchungen sowie Morphometrien durchgefuhrt. Es wurden Faszienverhaltnisse und Nervenverlaufe analysiert. Ergebnisse: Die neurovaskularen Bundel zeigen als Auslaufer des Plexus hypo gastricus inferior die Hochste Dichte von Nervengewebe. Am lateralen Rand der Denonvilliers-Faszie treten sie unter der Fascia pelvis parietalis hervor. Za…

Structural adaptations in the murine colon microcirculation associated with hapten-induced inflammation

Objectives: Blood flowing across the vascular endothelium creates wall shear stress, dependent on flow velocity and vessel geometry, that tends to disrupt lymphocyte-endothelial cell adhesion. To identify structural adaptations during acute colitis that may facilitate transmigration, we investigated the microcirculation in a murine model of acute colitis. Methods: In trinitrobenzenesulfonic acid (TNBS)- induced acute colitis, the infiltrating cells and colonic microcirculation was investigated by cellular topographic mapping as well as corrosion casting and 3- dimensional (3D) scanning electron microscopy. Colonic blood velocimetry was performed using intravital microscopy. Results: Clinica…

Blood flow shapes intravascular pillar geometry in the chick chorioallantoic membrane.

The relative contribution of blood flow to vessel structure remains a fundamental question in biology. To define the influence of intravascular flow fields, we studied tissue islands--here defined as intravascular pillars--in the chick chorioallantoic membrane. Pillars comprised 0.02 to 0.5% of the vascular system in 2-dimensional projection and were predominantly observed at vessel bifurcations. The bifurcation angle was generally inversely related to the length of the pillar (R = -0.47, P .05). 3-dimensional computational flow simulations indicated that the intravascular pillars were located in regions of low shear stress. Both wide-angle and acute-angle models mapped the pillars to regio…

External stenting with a new polyester mesh reduces neointimal hyperplasia of vein grafts in a sheep model.

Objective External stents placed around vein grafts have demonstrated effectiveness in reducing neointimal hyperplasia by preventing distension of the thin-walled vein grafts when exposed to arterial pressure. However, the ideal stent material has yet to be defined. The following study investigates the short- and long-term effects of an innovative polyester mesh stent designed with optimized adaptation of circumferential compliance. Methods Following in vitro definition of the ideal macro-porous polyester stent material, a total of 12 sheep underwent implantation of bilateral carotid artery vein graft bypasses. In six sheep, the short-term outcome (four weeks of implantation) was investigat…

Molecular Imaging in the Regenerating Post Pneumonectomy Lung

Intravascular pillars and pruning in the extraembryonic vessels of chick embryos.

To investigate the local mechanical forces associated with intravascular pillars and vessel pruning, we studied the conducting vessels in the extraembryonic circulation of the chick embryo. During the development days 13-17, intravascular pillars and blood flow parameters were identified using fluorescent vascular tracers and digital time-series video reconstructions. The geometry of selected vessels was confirmed by corrosion casting and scanning electron microscopy. Computational simulations of pruning vessels suggested that serial pillars form along pre-existing velocity streamlines; blood pressure demonstrated no obvious spatial relationship with the intravascular pillars. Modeling a Re…

Improved Regeneration of Autologous Nerve Transplants by Means of VEGF-Gene Therapy

The impact of the Vascular Endothelial Growth Factor (VEGF) on the angiogenic cascade is proven. Recently its neuroprotective effect after peripheral nerve injuries on α-motoneurons in the spinal cord was shown. Experiments on α-motoneurons demonstrated a decreased sensitivity to ischemia under VEGF-therapy. Aim of the study was to elucidate the effect of a localized VEGF-gene-therapy using an adenoviral vector construct in the model of a peripheral nerve defect in the rat treated with an autologous nerve transplant.

Dextran sulfate sodium leads to chronic colitis and pathological angiogenesis in Endoglin heterozygous mice

Pathological angiogenesis is an intrinsic component of chronic intestinal inflammation, which results in remodeling and expansion of the gut microvascular bed. Endoglin is essential for endothelial cell function and physiological angiogenesis. In this study we investigated its potential role in the regulation of inflammation by testing the response of Endoglin heterozygous (Eng(+/-)) mice to experimental colitis.C57BL/6 Eng(+/-) and littermate control mice drank water supplemented with 3% dextran sulfate sodium (DSS) for 5 days and were monitored for up to 26 days for clinical signs of colitis. Inflammation, crypt damage, and angiogenic index were scored on histological sections of distal c…

Searching for the right timing of surgical delay: angiogenesis, vascular endothelial growth factor and perfusion changes in a skin-flap model.

Summary Background The angiogenic potential of vascular endothelial growth factor (VEGF) and its oxygen pressure-dependent regulation suggest a strong connection between this growth factor and the ‘delay phenomenon'. In this study we focused on the chronological changes in VEGF concentration and flap perfusion in order to optimise the duration of surgical delay. Methods The VEGF concentration in skin and underlying muscle was measured in oversized, random-pattern flaps on 38 male Sprague-Dawley rats after 3, 5 or 7 days of surgical delay. Additionally, flaps were raised 5 or 7 days past preconditioning. The effect on flap perfusion was measured using indocyanine green fluoroscopy and the si…

Optimization of the Ussing chamber setup with excised rat intestinal segments for dissolution/permeation experiments of poorly soluble drugs.

AbstractContext: Prediction of the in vivo absorption of poorly soluble drugs may require simultaneous dissolution/permeation experiments. In vivo predictive media have been modified for permeation experiments with Caco-2 cells, but not for excised rat intestinal segments.Objective: The present study aimed at improving the setup of dissolution/permeation experiments with excised rat intestinal segments by assessing suitable donor and receiver media.Methods: The regional compatibility of rat intestine in Ussing chambers with modified Fasted and Fed State Simulated Intestinal Fluids (Fa/FeSSIFmod) as donor media was evaluated via several parameters that reflect the viability of the excised in…

CD34+ progenitor to endothelial cell transition in post-pneumonectomy angiogenesis.

In many species, pneumonectomy triggers compensatory lung growth that results in an increase not only in lung volume, but also in alveolar number. Whether the associated alveolar angiogenesis involves the contribution of blood-borne progenitor cells is unknown. To identify and characterize blood-borne progenitor cells contributing to lung growth after pneumonectomy in mice, we studied wild-type and wild-type/green fluorescence protein (GFP) parabiotic mice after left pneumonectomy. Within 21 days of pneumonectomy, a 3.2-fold increase occurred in the number of lung endothelial cells. This increase in total endothelial cells was temporally associated with a 7.3-fold increase in the number of …

Structural contribution of intravascular blood distension to lung mechanics

Binostril versus mononostril approaches in endoscopic transsphenoidal pituitary surgery: clinical evaluation and cadaver study.

OBJECTIVE Over the past 2 decades, endoscopy has become an integral part of the surgical repertoire for skull base procedures. The present clinical evaluation and cadaver study compare binostril and mononostril endoscopic transnasal approaches and the surgical techniques involved. METHODS Forty patients with pituitary adenomas were treated with either binostril or mononostril endoscopic surgery. Neurosurgical, endocrinological, ophthalmological, and neuroradiological examinations were performed. Ten cadaver specimens were prepared, and surgical aspects of the preparation and neuroradiological examination were documented. RESULTS In the clinical evaluation, 0° optics were optimal in the nas…

Quantitation of Microcomputed Tomography-Imaged Ocular Microvasculature

To quantitatively assess microvascular dimensions in the eyes of neonatal wild-type and VEGF(120)-tg mice, using a novel combination of techniques which permit three-dimensional (3D) image reconstruction.A novel combination of techniques was developed for the accurate 3D imaging of the microvasculature and demonstrated on the hyaloid vasculature of the neonatal mouse eye. Vascular corrosion casting is used to create a stable replica of the vascular network and X-ray microcomputed tomography (muCT) to obtain the 3D images. In-house computer-aided image analysis techniques were then used to perform a quantitative morphological analysis of the images.With the use of these methods, differences …

Comparison of endoscopic and open resection for Haglund tuberosity in a cadaver study.

Background: About half of patients who have Haglund disease may require treatment by surgical resection of the superior portion of the calcaneal tuberosity. Endoscopic techniques have been described as alternatives to open surgery, but only results of uncontrolled retrospective clinical investigations have been reported. Up to now no research is available which compares these different procedures. Methods: A controlled laboratory study was done to evaluate the morphologic appearance of the superior portion of the calcaneal tuberosity after endoscopic or open resection. The tuberosity was resected in 15 isolated fresh-frozen human cadaver lower limb specimens with either open (nine) or endos…

Scaffolding Effect of Vascular Distension on Peripheral Lung Mechanics

Computational analysis of lung deformation after murine pneumonectomy. [corrected].

In many mammalian species, the removal of one lung (pneumonectomy) is associated with the compensatory growth of the remaining lung. To investigate the hypothesis that parenchymal deformation may trigger lung regeneration, we used microCT scanning to create 3-dimensional finite element geometric models of the murine lung pre- and post-pneumonectomy (24 hours). The structural correspondence between models was established using anatomic landmarks and an iterative computational algorithm. When compared with the pre-pneumonectomy lung, the post-pneumonectomy models demonstrated significant translation and rotation of the cardiac lobe into the post-pneumonectomy pleural space. 2-dimensional maps…

Entrapment of adult fingers between window glass and seal entry of a motor vehicle side door: an experimental study for investigation of the force at the subjective pain threshold.

In modern motor vehicles with automatic power windows, a potential hazard exists for jam events of fingers between the window glass and seal entry. This study determined entrapment forces acting on adult fingers at the subjective maximum pain threshold during entrapment in such windows. The length and the girth of the proximal and distal interphalangeal joints of the triphalangeal fingers of the right hands of 109 participants (60 men, 49 women) were measured; the diameter was calculated from girth, which was assumed to be circular. The automatic power window system of a motor vehicle side door was changed to a mechanical system. During entrapment the force distributed across the four proxi…

Mechanical Evidence Of Microstructural Remodeling During Post-Pneumonectomy Compensatory Lung Growth

Endovascular Aneurysm Repair

Background — The purpose of the present study was to systematically analyze the histopathologic organization processes in excluded aneurysms after endovascular stenting and to develop a noninvasive monitoring method for these processes using MRI. Methods and Results — In 36 mongrel dogs, autologous aortic aneurysms were created. Endovascular treatment was performed using covered stents. Follow-up was after 1 week, 6 weeks, and 6 months. MRI was performed with T 2 -weighted turbo-spin-echo sequences and T 1 -weighted spin-echo sequences and was repeated after contrast bolus with gadolinium. Histopathologic findings were correlated to signal intensities (SIs) of MRI images. SIs of distinct a…

Effects of the novel polymer gel LeGoo on human internal thoracic arteries.

Purpose Established hemostatic devices can injure vessel wall integrity. LeGoo (Pluromed, Woburn, MA), a novel poloxamer gel with reverse thermosensitive properties, is a new device for temporary occlusion of blood vessels. The present study investigated the effects of LeGoo on vascular function and morphology. Description The distal end of the human internal thoracic artery was used to assess vascular function of LeGoo-applied segments in organ bath experiments and by scanning electron microscopy. Evaluation After LeGoo application, both maximal contractile responses to noradrenaline and endothelium-dependent relaxant responses to acetylcholine were significantly reduced. Scanning electron…

Resection of the mesopancreas (RMP): a new surgical classification of a known anatomical space

Abstract Background Prognosis after surgical therapy for pancreatic cancer is poor and has been attributed to early lymph node involvement as well as to a strong tendency of cancer cells to infiltrate into the retropancreatic tissue and to spread along the peripancreatic neural plexuses. The objective of our study was to classify the anatomical-surgical layer of the mesopancreas and to describe the surgical principles relevant for resection of the mesopancreas (RMP). Immunohistochemical investigation of the mesopancreatic-perineural lymphogenic structures was carried out with the purpose of identifying possible routes of metastatic spread. Methods Resection of the mesopancreas (RMP) was per…

Cross-circulation and Cell Distribution Kinetics in Parabiotic Mice

Blood-borne nucleated cells participate not only in inflammation, but in tissue repair and regeneration. Because progenitor and stem cell populations have a low concentration in the blood, the circulation kinetics and tissue distribution of these cells is largely unknown. An important approach to tracking cell lineage is the use of fluorescent tracers and parabiotic models of cross-circulation. Here, we investigated the cross-circulation and cell distribution kinetics of C57/B6 GFP(+)/wild-type parabionts. Flow cytometry analysis of the peripheral blood after parabiosis demonstrated no evidence for a "parabiotic barrier" based on cell size or surface characterstics; all peripheral blood cel…

Dynamic determination of oxygenation and lung compliance in murine pneumonectomy.

Thoracic surgical procedures in mice have been applied to a wide range of investigations, but little is known about the murine physiologic response to pulmonary surgery. Using continuous arterial oximetry monitoring and the FlexiVent murine ventilator, the authors investigated the effect of anesthesia and pneumonectomy on mouse oxygen saturation and lung mechanics. Sedation resulted in a dose-dependent decline of oxygen saturation that ranged from 55% to 82%. Oxygen saturation was restored by mechanical ventilation with increased rate and tidal volumes. In the mouse strain studied, optimal ventilatory rates were a rate of 200/minute and a tidal volume of 10 mL/kg. Sustained inflation pressu…

Restoration of cerebral and systemic microvascular architecture in APP/PS1 transgenic mice following treatment with Liraglutide™.

OBJECTIVE: Cerebral microvascular impairments occurring in AD may reduce Aβ peptide clearance and impact upon circulatory ultrastructure and function. We hypothesized that microvascular pathologies occur in organs responsible for systemic Aβ peptide clearance in a model of AD and that Liraglutide (Victoza(®)) improves vessel architecture. METHODS: Seven-month-old APP/PS1 and age-matched wild-type mice received once-daily intraperitoneal injections of either Liraglutide or saline (n = 4 per group) for eight weeks. Casts of cerebral, splenic, hepatic, and renal microanatomy were analyzed using SEM. RESULTS: Casts from wild-type mice showed regularly spaced microvasculature with smooth lumenal…