Vitamins E and C - effects on matrix components in the vascular system

USDA-ARS?s Scientific Manuscript database

The connective tissue in the vascular system, consisting mainly of vascular smooth muscle cells (VSMC) and the interstitial extracellular matrix (ECM), plays important roles in the maintenance of an intact vascular wall as well as in the repair of atherosclerotic lesions during disease development. ...

Predicting survival across chronic interstitial lung disease: the ILD-GAP model.

PubMed

Ryerson, Christopher J; Vittinghoff, Eric; Ley, Brett; Lee, Joyce S; Mooney, Joshua J; Jones, Kirk D; Elicker, Brett M; Wolters, Paul J; Koth, Laura L; King, Talmadge E; Collard, Harold R

2014-04-01

Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206), connective tissue disease-associated ILD (n=281), idiopathic nonspecific interstitial pneumonia (n=45), or unclassifiable ILD (n=173) were selected from an ongoing database (N=1,012). Performance of the previously validated GAP model was compared with novel prediction models in each ILD subtype and the combined cohort. Patients with follow-up pulmonary function data were used for longitudinal model validation. The GAP model had good performance in all ILD subtypes (c-index, 74.6 in the combined cohort), which was maintained at all stages of disease severity and during follow-up evaluation. The GAP model had similar performance compared with alternative prediction models. A modified ILD-GAP Index was developed for application across all ILD subtypes to provide disease-specific survival estimates using a single risk prediction model. This was done by adding a disease subtype variable that accounted for better adjusted survival in connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, and idiopathic nonspecific interstitial pneumonia. The GAP model accurately predicts risk of death in chronic ILD. The ILD-GAP model accurately predicts mortality in major chronic ILD subtypes and at all stages of disease.

Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow

PubMed Central

Kwee, Ingrid L.

2017-01-01

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics. PMID:28820467

Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow.

PubMed

Nakada, Tsutomu; Kwee, Ingrid L; Igarashi, Hironaka; Suzuki, Yuji

2017-08-18

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics.

The relevance of light diffusion profiles for interstitial PDT using light-diffusing optical fibers

NASA Astrophysics Data System (ADS)

Stringasci, Mirian D.; Fortunato, Thereza C.; Moriyama, Lilian T.; Vollet Filho, José Dirceu; Bagnato, Vanderlei S.; Kurachi, Cristina

2017-02-01

Photodynamic therapy (PDT) is a technique used for several tumor types treatment. Light penetration on biological tissue is one limiting factor for PDT applied to large tumors. An alternative is using interstitial PDT, in which optical fibers are inserted into tumors. Cylindrical diffusers have been used in interstitial PDT. Light emission of different diffusers depends on the manufacturing process, size and optical properties of fibers, which make difficult to establish an adequate light dosimetry, since usually light profile is not designed for direct tissue-fiber contact. This study discusses the relevance of light distribution by a cylindrical diffuser into a turbid lipid emulsion solution, and how parts of a single diffuser contribute to illumination. A 2 cm-long cylindrical diffuser optical fiber was connected to a diode laser (630 nm), and the light spatial distribution was measured by scanning the solution with a collection probe. From the light field profile generated by a 1 mm-long intermediary element of a 20 mm-long cylindrical diffuser, recovery of light distribution for the entire diffuser was obtained. PDT was performed in rat healthy liver for a real treatment outcome analysis. By using computational tools, a typical necrosis profile generated by the irradiation with such a diffuser fiber was reconstructed. The results showed that it was possible predicting theoretically the shape of a necrosis profile in a healthy, homogeneous tissue with reasonable accuracy. The ability to predict the necrosis profile obtained from an interstitial illumination by optical diffusers has the potential improve light dosimetry for interstitial PDT.

Microstructures of Randall's plaques and their interfaces with calcium oxalate monohydrate kidney stones reflect underlying mineral precipitation mechanisms.

PubMed

Sethmann, Ingo; Wendt-Nordahl, Gunnar; Knoll, Thomas; Enzmann, Frieder; Simon, Ludwig; Kleebe, Hans-Joachim

2017-06-01

Randall's plaques (RP) are preferred sites for the formation of calcium oxalate monohydrate (COM) kidney stones. However, although processes of interstitial calcium phosphate (CaP) plaque formation are not well understood, the potential of plaque microstructures as indicators of CaP precipitation conditions received only limited attention. We investigated RP-associated COM stones for structural details of the calcified tissues and microstructural features of plaque-stone interfaces as indicators of the initial processes of stone formation. Significantly increased CaP supersaturation can be expected for interstitial fluid, if reabsorbed ions from the tubular system continuously diffuse into the collagenous connective tissue. Densely packed, fine-grained CaP particles were found in dense textures of basement membranes while larger, laminated particles were scattered in coarse-meshed interstitial tissue, which we propose to be due to differential spatial confinements and restrictions of ion diffusion. Particle morphologies suggest an initial precipitation as metastable amorphous calcium phosphate (ACP). Morphologies and arrangements of first COM crystals at the RP-stone interface ranged from stacked euhedral platelets to skeletal morphologies and even porous, dendritic structures, indicating, in this order, increasing levels of COM supersaturation. Furthermore, these first COM crystals were often coated with CaP. On this basis, we propose that ions from CaP-supersaturated interstitial fluid may diffuse through porous RP into the urine, where a resulting local increase in COM supersaturation could trigger crystal nucleation and, hence, initiate stone formation. Ion-depleted fluid in persistent pores of initial COM layers may get replenished from interstitial fluid, leading to CaP precipitation in porous COM.

Probe for Sampling of Interstitial Fluid From Bone

NASA Technical Reports Server (NTRS)

Janle, Elsa M.

2004-01-01

An apparatus characterized as both a membrane probe and a bone ultrafiltration probe has been developed to enable in vivo sampling of interstitial fluid in bone. The probe makes it possible to measure the concentration of calcium and other constituents of the fluid that may be relevant to bone physiology. The probe could be especially helpful in experimental studies of microgravitational bone loss and of terrestrial bone-loss disease states, including osteoporosis. The probe can be implanted in the bone tissue of a living animal and can be used to extract samples of the interstitial bone fluid from time to time during a long-term study. The probe includes three 12-cm-long polyacrylonitrile fibers configured in a loop form and attached to polyurethane tubing [inside diameter 0.025 in. (0.64 mm), outside diameter 0.040 in. (1 mm)]; the attachment is made by use of a 1-cm-long connecting piece of polyurethane tubing [inside diameter 0.035 0.003 in. (0.89 0.08 mm), outside diameter 0.060 0.003 in. (1.52 0.08 mm)]. At the distal end, a 2-cm-long piece of polyurethane tubing of the same inner and outer diameters serves as a connector to a hub. A 1-cm long piece of expanded poly (tetrafluoroethylene) tubing over the joint between the fibers and the connecting tubing serves as a tissue-in-growth site.

Connective tissue of cervical carcinoma xenografts: associations with tumor hypoxia and interstitial fluid pressure and its assessment by DCE-MRI and DW-MRI.

PubMed

Hompland, Tord; Ellingsen, Christine; Galappathi, Kanthi; Rofstad, Einar K

2014-01-01

Abstract Background. A high fraction of stroma in malignant tissues is associated with tumor progression, metastasis, and poor prognosis. Possible correlations between the stromal and physiologic microenvironments of tumors and the potential of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in quantification of the stromal microenvironment were investigated in this study. Material and methods. CK-160 cervical carcinoma xenografts were used as preclinical tumor model. A total of 43 tumors were included in the study, and of these tumors, 17 were used to search for correlations between the stromal and physiologic microenvironments, 11 were subjected to DCE-MRI, and 15 were subjected to DW-MRI. DCE-MRI and DW-MRI were carried out at 1.5 T with a clinical MR scanner and a slotted tube resonator transceiver coil constructed for mice. Fraction of connective tissue (CTFCol) and fraction of hypoxic tissue (HFPim) were determined by immunohistochemistry. A Millar SPC 320 catheter was used to measure tumor interstitial fluid pressure (IFP). Results. CTFCol showed a positive correlation to IFP and an inverse correlation to HFPim. The apparent diffusion coefficient assessed by DW-MRI was inversely correlated to CTFCol, whereas no correlation was found between DCE-MRI-derived parameters and CTFCol. Conclusion. DW-MRI is a potentially useful method for characterizing the stromal microenvironment of tumors.

Lung Ultrasonography in the Evaluation of Interstitial Lung Disease in Systemic Connective Tissue Diseases: Criteria and Severity of Pulmonary Fibrosis - Analysis of 52 Patients.

PubMed

Buda, N; Piskunowicz, M; Porzezińska, M; Kosiak, W; Zdrojewski, Z

2016-08-01

Patients with a diagnosed systemic connective tissue disease require regular monitoring from the point of view of interstitial lung disease. The main aim of this work is a description of the criteria for pulmonary fibrosis and the degree of the severity of the fibrosis during the course of interstitial lung disease through the TLU (transthoracic lung ultrasound). 52 patients with diagnosed diffuse interstitial lung disease were qualified for this research, together with 50 volunteers in the control group. The patients in both groups were over 18 years of age and were of both sexes. The results of the TLU of the patients underwent statistical analysis and were compared to High-Resolution Computed Tomography (HRCT) results. As a consequence of the statistical analysis, we defined our own criteria for pulmonary fibrosis in TLU: irregularity of the pleura line, tightening of the pleura line, the fragmentary nature of the pleura line, blurring of the pleura line, thickening of the pleura line, artifacts of line B ≤ 3 and ≥ 4, artifacts of Am line and subpleural consolidations < 5 mm. As a result of the conducted research, a scale of severity of pulmonary fibrosis in TLU was devised (UFI - Ultrasound Fibrosis Index), enabling a division to be made into mild, moderate and severe cases. Transthoracic Lung Ultrasonography (TLU) gives a new outlook on the diagnostic possibilities, non-invasive and devoid of ionising radiation, of pulmonary fibrosis. This research work has allowed to discover two new ultrasound symptoms of pulmonary fibrosis (blurred pleural line and Am lines). © Georg Thieme Verlag KG Stuttgart · New York.

Idiopathic Interstitial Pneumonia Associated With Autoantibodies: A Large Case Series Followed Over 1 Year.

PubMed

Collins, Bridget F; Spiekerman, Charles F; Shaw, Megan A; Ho, Lawrence A; Hayes, Jennifer; Spada, Carolyn A; Stamato, Caroline M; Raghu, Ganesh

2017-07-01

Some patients with autoimmune characteristics and idiopathic interstitial pneumonia, particularly usual interstitial pneumonia (UIP), do not fit neatly into the category of connective tissue disease-associated interstitial lung disease (CTD-ILD), idiopathic pulmonary fibrosis (IPF), or recently proposed yet to be validated criteria for interstitial pneumonia with autoimmune features (IPAF). Outcomes of these patients are unknown. This was a retrospective single-center study. Analyses of variance compared differences in mean change in FVC and diffusion capacity (Dlco) over 1 year among 124 well-defined patients (20 patients with positive autoantibodies with or without symptoms of connective tissue disease [AI-ILD], 15 patients with IPAF, 36 patients with CTD-ILD, and 53 patients with IPF with negative CTD serologies [Lone-IPF]). Of the patients, 75% with AI-ILD, 33% with IPAF, and 33% with CTD-ILD had UIP. Initial FVC and Dlco were similarly moderately reduced across groups. Mean change in FVC over 12 months was as follows: -60 mL (IPAF), -110 mL (AI-ILD), -10 mL (CTD-ILD), and -90 mL (Lone-IPF) (P = .52). Mean change in Dlco was as follows: 2.39 mL/mm Hg/min (IPAF), -1.15 mL/mm Hg/min (AI-ILD), -0.27 mL/mm Hg/min (CTD-ILD), and -1.05 mL/mm Hg/min (Lone-IPF) (P < .001). By pattern of disease, the mean change in FVC was as follows: -140 mL (UIP), 10 mL (nonspecific interstitial pneumonia), and 12 mL (unclassifiable/other) (P = .001). No clinically significant differences in pulmonary function to distinguish between patients with AI-ILD, IPAF, CTD-ILD, and Lone-IPF were observed after 1 year. Longer periods of follow-up are needed to understand the outcomes of these patients. It is not yet clear whether AI-ILD is a distinct phenotype or a variant of the newly proposed entity IPAF. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

PubMed

Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network

PubMed Central

Soltani, M.; Chen, P.

2013-01-01

Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor’s surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy’s law for tissue, and simplified Navier–Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model. PMID:23840579

Calcium channel blockers and esophageal sclerosis: should we expect exacerbation of interstitial lung disease?

PubMed

Seretis, Charalampos; Seretis, Fotios; Gemenetzis, George; Liakos, Nikolaos; Pappas, Apostolos; Gourgiotis, Stavros; Lagoudianakis, Emmanuel; Keramidaris, Dimitrios; Salemis, Nikolaos

2012-01-01

Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

A long-distance fluid transport pathway within fibrous connective tissues in patients with ankle edema.

PubMed

Li, Hongyi; Yang, Chongqing; Lu, Kuiyuan; Zhang, Liyang; Yang, Jiefu; Wang, Fang; Liu, Dongge; Cui, Di; Sun, Mingjun; Pang, Jianxin; Dai, Luru; Han, Dong; Liao, Fulong

2016-10-05

Although the microcirculatory dysfunctions of edema formation are well documented, the draining pattern of dermal edema lacks information. This study was to assess the potential drainage pathways of the interstitial fluid in patients with ankle edema using the anatomical and histological methods. Four amputees of lower leg participated in this study. Fluorescent imaging agent was injected into lateral ankle dermis in one volunteered patient before the amputation and three lower legs after the amputation. Physiologically in the volunteer or enhanced by cyclical compression on three amputated limbs, several fluorescent longitudinal pathways from ankle dermis to the broken end of the amputated legs were subsequently visualized and studied using histological methods, laser confocal microscopy and electron microscopy methods respectively. Interestingly, the fluorescent pathways confirmed to be fibrous connective tissues and the presence of two types: those of the cutaneous pathway (located in dermis or the interlobular septum among adipose tissues within the hypodermis) and those of the perivascular pathway (located in connective tissues surrounding the veins and the arteries). The intrinsic three-dimensional architecture of each fluorescent pathway was the longitudinally running and interconnected fibril bundles, upon which, an interfacial transport pathway within connective tissues was visualized by fluorescein. The current anatomical data suggested that a unique long-distance transport pathway composed of oriented fibrous connective tissues might play a pathophysiological role in draining dermal edema besides vascular circulations and provide novel understandings of general fibrous connective tissues in life science.

Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

PubMed

Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

2016-03-01

It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p < 0.008 and p < 0.001, respectively). There was no statistically significant difference between the KL-6 levels in the healthy control group and the CTD without pulmonary involvement group (p = 0.289). The KL-6 levels did not differ significantly according to the connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

Casting core for a cooling arrangement for a gas turbine component

DOEpatents

Lee, Ching-Pang; Heneveld, Benjamin E

2015-01-20

A ceramic casting core, including: a plurality of rows (162, 166, 168) of gaps (164), each gap (164) defining an airfoil shape; interstitial core material (172) that defines and separates adjacent gaps (164) in each row (162, 166, 168); and connecting core material (178) that connects adjacent rows (170, 174, 176) of interstitial core material (172). Ends of interstitial core material (172) in one row (170, 174, 176) align with ends of interstitial core material (172) in an adjacent row (170, 174, 176) to form a plurality of continuous and serpentine shaped structures each including interstitial core material (172) from at least two adjacent rows (170, 174, 176) and connecting core material (178).

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis

PubMed Central

YANG, ZHIZHOU; SUN, ZHAORUI; LIU, HONGMEI; REN, YI; SHAO, DANBING; ZHANG, WEI; LIN, JINFENG; WOLFRAM, JOY; WANG, FENG; NIE, SHINAN

2015-01-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson’s trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury. PMID:25815693

Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).

PubMed

Mace, T F

1976-01-01

Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.

[Diagnostic difficulties in polymyositis].

PubMed

Majewski, Dominik; Puszczewicz, Mariusz; Tuchocka-Piotrowska, Aleksandra; Kołczewska, Aleksandra

2006-01-01

Polymyositis is a connective tissue disease. Although myositis is the dominant clinical manifestation, internal organs may also be affected. Arthritis occurs in 30% of patients, especially in the course of the anti-synthetase syndrome. We report on a case of a woman with polymyositis and interstitial lung disease. Arthritis and the presence of anti-cyclic citrullinated peptide antibodies in the patient's serum may suggest the diagnosis of the overlap syndrome.

Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

PubMed

Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

2018-02-01

Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

Usual interstitial pneumonia: typical, possible, and “inconsistent” patterns

PubMed Central

Torres, Pedro Paulo Teixeira e Silva; Rabahi, Marcelo Fouad; Moreira, Maria Auxiliadora Carmo; Meirelles, Gustavo de Souza Portes; Marchiori, Edson

2017-01-01

ABSTRACT Idiopathic pulmonary fibrosis is a severe and progressive chronic fibrosing interstitial lung disease, a definitive diagnosis being established by specific combinations of clinical, radiological, and pathological findings. According to current international guidelines, HRCT plays a key role in establishing a diagnosis of usual interstitial pneumonia (UIP). Current guidelines describe three UIP patterns based on HRCT findings: a typical UIP pattern; a pattern designated “possible UIP”; and a pattern designated “inconsistent with UIP”, each pattern having important diagnostic implications. A typical UIP pattern on HRCT is highly accurate for the presence of histopathological UIP, being currently considered to be diagnostic of UIP. The remaining patterns require further diagnostic investigation. Other known causes of a UIP pattern include drug-induced interstitial lung disease, chronic hypersensitivity pneumonitis, occupational diseases (e.g., asbestosis), and connective tissue diseases, all of which should be included in the clinical differential diagnosis. Given the importance of CT studies in establishing a diagnosis and the possibility of interobserver variability, the objective of this pictorial essay was to illustrate all three UIP patterns on HRCT. PMID:29160385

Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

PubMed

Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.

PubMed

Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid; LeSage, Daphne; Sarver, Catherine; Phillips, Kristine; Strand, Vibeke; Matteson, Eric L

2014-04-01

Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

Development of Clinical Trial Assessments for the Study of Interstitial Lung Disease in Patients who have Connective Tissue Diseases-Methodological Considerations.

PubMed

Huscher, Dörte; Saketkoo, Lesley Ann; Pittrow, David; Khanna, Dinesh

2010-05-01

This review article discusses the proposed methodology that will be utilized to develop core set items for connective tissue disease-associated interstitial lung disease (CTD-ILD). CTD-ILD remain an important enigma in clinical medicine. No consensus exists on measurement of disease activity or what constitutes a significant response to therapeutic interventions. Lack of appropriate measures inhibit effective drug development and hamper regulatory evaluation of candidate therapies.An interdisciplinary and international Steering Committee (SC) will oversee the execution of a 3-tier Delphi exercise involving experts in CTD and ILD. In parallel to the Delphi, qualitative information will be gathered from patients with ILD using focus groups. These data will subsequently be used to construct surveys to collect quantitative response from patients with ILD. The final Delphi and Patient Perspective results are to be scrutinized by SC and specialty sub-groups (including patient advocates) for truth, discrimination and feasibility - the OMERACT filters. Through application of Nominal Group technique, a core set of outcome measures will be proposed. Subsequent exercises will evaluate the applicability of a proposed core set to the unique issues posed by individual CTDs in addition to guidelines on screening, prognostication and damage scoring.

Anti-fibrotic effects of pirfenidone by interference with the hedgehog signalling pathway in patients with systemic sclerosis-associated interstitial lung disease.

PubMed

Xiao, Hua; Zhang, Guang-Feng; Liao, Xiang-Ping; Li, Xiao-Jie; Zhang, Jian; Lin, Haobo; Chen, Zhe; Zhang, Xiao

2018-02-01

To determine whether pirfenidone attenuates lung fibrosis by interfering with the hedgehog (Hh) signalling pathway in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Twenty-five SSc-ILD patients (20 first visit, five who underwent pirfenidone treatment for 6 months) and 10 healthy controls were recruited. Lung tissues were obtained by open-chest surgery, and primary lung fibroblasts were isolated, cultured and stimulated with pirfenidone. The levels of the proteins glioma-associated oncogene 1 (GLI1), suppressor of fused (Sufu), α-smooth muscle actin, and fibronectin in lung tissues or fibroblasts were determined by Western blotting. The messenger RNA levels of GLI1, glioma-associated oncogene 2, protein patched homolog 1, and Sufu in lung tissues or fibroblasts were determined by quantitative reverse-transcription polymerase chain reaction. Meanwhile, the levels of phosphorylation glycogen synthase kinasep-3β (pGSK-3β), phosphorylation SMAD2 (pSMAD2), and phosphorylation c-Jun N-terminal kinase (pJNK) in fibroblasts were determined by Western blotting. Hh pathway activation was increased in the lung tissue of SSc-ILD patients and was decreased by pirfenidone, Sufu was upregulated in lung fibroblasts isolated from SSc-ILD patients after pirfenidone challenge, and pirfenidone inhibited the phosphorylation of GSK-3β signalling. Pirfenidone has anti-fibrotic effects in SSc-ILD patients by interfering with both the Hh signalling pathway and the GSK-3β signalling pathway via the regulation of Sufu expression. These results might promote its use in other Hh driven lung diseases such as idiopathic pulmonary fibrosis and especially the interstitial lung disease associated with connective tissue diseases. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report.

PubMed

Thongpooswan, Supat; Tushabe, Rachel; Song, Jeffrey; Kim, Paul; Abrudescu, Adriana

2015-08-06

Mixed connective tissue disease (MCTD) is a connective tissue disorder characterized by high titers of distinct antibodies: U1 ribonucleoprotein with clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. The association of SLE and DM with various cancers of the thyroid has been reported in the literature. However, there have been no reports associating MCTD with thyroid cancer. We present a 58-year-old woman diagnosed with MCTD with co-morbid interstitial lung disease that has remained stable for 10 years, who developed papillary thyroid carcinoma (PTC) 10 years after initial diagnosis. We theorize that: 1) MCTD may have been a primary diagnosis complicated by PTC, or 2) MCTD may have been an initial presentation of paraneoplastic syndrome of silent PTC, because her symptoms of MCTD significantly improved after total thyroidectomy. To the best of our knowledge, this is the first case report to associate MCTD with PTC. It highlights the importance of maintaining a high index of suspicion for thyroid malignancy in MCTD patients.

Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease.

PubMed

Oldham, Justin M; Lee, Cathryn; Valenzi, Eleanor; Witt, Leah J; Adegunsoye, Ayodeji; Hsu, Scully; Chen, Lena; Montner, Steven; Chung, Jonathan H; Noth, Imre; Vij, Rekha; Strek, Mary E

2016-12-01

Azathioprine is a commonly prescribed therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). Combination therapy that included azathioprine was recently shown to increase the risk of death and hospitalization in patients with idiopathic pulmonary fibrosis. Whether azathioprine increases the risk of adverse outcomes in patients with fibrotic CTD-ILD, including those with CTD-associated usual interstitial pneumonia (UIP), remains unknown. A retrospective cohort analysis was performed to determine the combined incidence rate of death, transplant and respiratory hospitalization associated with azathioprine exposure. A fibrotic CTD-ILD cohort treated with mycophenolate mofetil served as a comparator group. Incidence rates were compared with an incidence rate ratio (IRR) generated by negative binomial regression. Longitudinal pulmonary function response was then assessed using mixed effects linear regression models. Fifty-four patients were treated with azathioprine and forty-three with mycophenolate. Medication discontinuation due to non-respiratory side effects occurred in 27% and 5% of the azathioprine and mycophenolate cohorts, respectively. The combined incidence rate of adverse outcomes was 0.015 and 0.013 for azathioprine and mycophenolate, respectively (IRR 1.23; 95% CI 0.49-3.12; p = 0.66). Similar incidence rates were observed among those with CTD-UIP (IRR 0.83; 95% CI 0.21-3.31; p = 0.79). Both groups demonstrated pulmonary function stability over time, with the azathioprine group demonstrating a marginal improvement. A significant minority of patients could not tolerate azathioprine due to non-respiratory side effects. Of those who did tolerate azathioprine, a similar incidence of adverse outcomes was observed as those treated with mycophenolate. Both therapies were associated with stability in pulmonary function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Blood and interstitial flow in the hierarchical pore space architecture of bone tissue.

PubMed

Cowin, Stephen C; Cardoso, Luis

2015-03-18

There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

Blood and Interstitial flow in the hierarchical pore space architecture of bone tissue

PubMed Central

Cowin, Stephen C.; Cardoso, Luis

2015-01-01

There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. PMID:25666410

[Effect of fluorofenidone on renal interstitial fibrosis in rats with unilateral ureteral obstruction].

PubMed

Tan, Wenqing; Wang, Wei; Zheng, Xuan; Chen, Jiying; Yuan, Xiangning; Zhang, Fangfang; Wang, Shuting; Tao, Lijian

2018-05-28

To investigate the effect of fluorofenidone on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) and to observe the effect of fluorofenidone on the expressions of collagen type I (Col I), collagen type III (Col III), α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF) in the renal tissues of UUO rats.
 Methods: Male Sprague-Dawley (SD) rats were randomly divided into a sham-operated group, a UUO group, and a flurofenidone group (n=5). UUO model was induced by ligating the left ureter in rats. The rats were treated with 125 mg/(kg.d) fluorofenidone by gastric gavage in the fluorofenidone group at 24 h before the operation, and the rats were treated with the identical dose of 0.5% sodium carboxyl methyl cellulose (CMC-Na) in the other 2 groups. The rats were sacrificed at 14 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the mRNA expressions of Col I, Col III, α-SMA, PDGF and CTGF were detected by real-time PCR, and the protein expressions of Col I, Col III, PDGF and CTGF were detected by immunohistochemical staining.
 Results: The renal interstitial damage index, relative collagen area and mRNA and protein expressions of Col I and Col III in the renal tissues of the rats in the UUO group significantly increased (P<0.05), and fluorofenidone could reduce these indexes (P<0.05). Compared with the sham-operated group, the protein expressions of α-SMA, PDGF, CTGF and the mRNA expressions of PDGF and CTGF in the renal tissues of the rats in the UUO group were increased, but fluorofenidone could decrease the protein expressions of α-SMA, PDGF, CTGF and the mRNA expressions of PDGF and CTGF (P<0.05).
 Conclusion: Fluorofenidone (125 mg/kg.d) could attenuate renal interstitial fibrosis through inhibition of fibroblast proliferation, myofibroblastic activation, PDGF and CTGF expression.

Role of interstitial branching in the development of visual corticocortical connections: a time-lapse and fixed-tissue analysis.

PubMed

Ruthazer, Edward S; Bachleda, Amelia R; Olavarria, Jaime F

2010-12-15

We combined fixed-tissue and time-lapse analyses to investigate the axonal branching phenomena underlying the development of topographically organized ipsilateral projections from area 17 to area 18a in the rat. These complementary approaches allowed us to relate static, large-scale information provided by traditional fixed-tissue analysis to highly dynamic, local, small-scale branching phenomena observed with two-photon time-lapse microscopy in acute slices of visual cortex. Our fixed-tissue data revealed that labeled area 17 fibers invaded area 18a gray matter at topographically restricted sites, reaching superficial layers in significant numbers by postnatal day 6 (P6). Moreover, most parental axons gave rise to only one or occasionally a small number of closely spaced interstitial branches beneath 18a. Our time-lapse data showed that many filopodium-like branches emerged along parental axons in white matter or deep layers in area 18a. Most of these filopodial branches were transient, often disappearing after several minutes to hours of exploratory extension and retraction. These dynamic behaviors decreased significantly from P4, when the projection is first forming, through the second postnatal week, suggesting that the expression of, or sensitivity to, cortical cues promoting new branch addition in the white matter is developmentally down-regulated coincident with gray matter innervation. Together, these data demonstrate that the development of topographically organized corticocortical projections in rats involves extensive exploratory branching along parental axons and invasion of cortex by only a small number of interstitial branches, rather than the widespread innervation of superficial cortical layers by an initially exuberant population of branches. © 2010 Wiley-Liss, Inc.

Role of Interstitial Branching in the Development of Visual Corticocortical Connections: A Time-Lapse and Fixed-Tissue Analysis

PubMed Central

Ruthazer, Edward S.; Bachleda, Amelia R.; Olavarria, Jaime F.

2013-01-01

We combined fixed-tissue and time-lapse analyses to investigate the axonal branching phenomena underlying the development of topographically organized ipsilateral projections from area 17 to area 18a in the rat. These complementary approaches allowed us to relate static, large-scale information provided by traditional fixed-tissue analysis to highly dynamic, local, small-scale branching phenomena observed with two-photon time-lapse microscopy in acute slices of visual cortex. Our fixed-tissue data revealed that labeled area 17 fibers invaded area 18a gray matter at topographically restricted sites, reaching superficial layers in significant numbers by postnatal day 6 (P6). Moreover, most parental axons gave rise to only one or occasionally a small number of closely spaced interstitial branches beneath 18a. Our time-lapse data showed that many filopodium-like branches emerged along parental axons in white matter or deep layers in area 18a. Most of these filopo-dial branches were transient, often disappearing after several minutes to hours of exploratory extension and retraction. These dynamic behaviors decreased significantly from P4, when the projection is first forming, through the second postnatal week, suggesting that the expression of, or sensitivity to, cortical cues promoting new branch addition in the white matter is developmentally down-regulated coincident with gray matter innervation. Together, these data demonstrate that the development of topographically organized corticocortical projections in rats involves extensive exploratory branching along parental axons and invasion of cortex by only a small number of interstitial branches, rather than the widespread innervation of superficial cortical layers by an initially exuberant population of branches. PMID:21031561

Connective Tissue Disease-associated Interstitial Lung Diseases (CTD-ILD) - Report from OMERACT CTD-ILD Working Group.

PubMed

Khanna, Dinesh; Mittoo, Shikha; Aggarwal, Rohit; Proudman, Susanna M; Dalbeth, Nicola; Matteson, Eric L; Brown, Kevin; Flaherty, Kevin; Wells, Athol U; Seibold, James R; Strand, Vibeke

2015-11-01

Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials (RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research. The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants. OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to < 10% relative decline in FVC and ≥ 15% relative decline in DLCO. There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.

Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis

PubMed Central

Yamakawa, Hideaki; Hagiwara, Eri; Kitamura, Hideya; Yamanaka, Yumie; Ikeda, Satoshi; Sekine, Akimasa; Baba, Tomohisa; Iso, Shinichiro; Okudela, Koji; Iwasawa, Tae; Takemura, Tamiko; Kuwano, Kazuyoshi; Ogura, Takashi

2016-01-01

Background Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. Objective This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. Methods We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. Results Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. Conclusion Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD. PMID:27564852

Interstitial Photoacoustic Sensor for the Measurement of Tissue Temperature during Interstitial Laser Phototherapy

PubMed Central

Li, Zhifang; Chen, Haiyu; Zhou, Feifan; Li, Hui; Chen, Wei R.

2015-01-01

Photothermal therapy is an effective means to induce tumor cell death, since tumor tissue is more sensitive to temperature increases than normal tissue. Biological responses depend on tissue temperature; target tissue temperature needs to be precisely measured and controlled to achieve desired thermal effects. In this work, a unique photoacoustic (PA) sensor is proposed for temperature measurement during interstitial laser phototherapy. A continuous-wave laser light and a pulsed laser light, for photothermal irradiation and photoacoustic temperature measurement, respectively, were delivered to the target tissue through a fiber coupler. During laser irradiation, the PA amplitude was measured. The Grüneisen parameter and the bioheat equation were used to determine the temperature in strategic positions in the target tissue. Our results demonstrate that the interstitial PA amplitude is a linear function of temperature in the range of 22 to 55 °C, as confirmed by thermocouple measurement. Furthermore, by choosing appropriate laser parameters, the maximum temperature surrounding the active diffuse fiber tip in tissue can be controlled in the range of 41 to 55 °C. Thus, this sensor could potentially be used for fast, accurate, and convenient three-dimensional temperature measurement, and for real-time feedback and control of interstitial laser phototherapy in cancer treatment. PMID:25756865

Immunohistochemical and ultrastructural characteristics of interstitial cells of Cajal in the rabbit duodenum. Presence of a single cilium

PubMed Central

Junquera, Concepción; Martínez-Ciriano, Carmen; Castiella, Tomás; Serrano, Pedro; Azanza, María Jesús; Ramón y Cajal Junquera, Santiago

2007-01-01

Abstract Santiago Ramón y Cajal discovered a new type of cell related to the myenteric plexus and also to the smooth muscle cells of the circular muscle layer of the intestine. Based on their morphology, relationships and staining characteristics, he considered these cells as primitive neurons. One century later, despite major improvements in cell biology, the interstitial cells of Cajal (ICCs) are still controversial for many researchers. The aim of study was to perform an immunohistochemical and ultrastructural characterization of the ICCs in the rabbit duo-denum. We have found interstitial cells that are positive for c-Kit, CD34 and nestin and are also positive for Ki67 protein, tightly associated with somatic cell proliferation. By means of electron microscopy, we describe ICCs around enteric ganglia. They present triangular or spindle forms and a very voluminous nucleus with scarce per-inuclear chromatin surrounded by a thin perinuclear cytoplasm that expands with long cytoplasmic processes. ICC processes penetrate among the smooth muscle cells and couple with the processes of other ICCs located in the connective tissue of the circular muscle layer and establish a three-dimensional network. Intercellular con-tacts by means of gap-like junctions are frequent. ICCs also establish gap-like junctions with smooth muscle cells. We also observe a population of interstitial cells of stellate morphology in the connective tissue that sur-rounds the muscle bundles in the circular muscle layer, usually close to nervous trunks. These cells establish different types of contacts with the muscle cells around them. In addition, the presence of a single cilium show-ing a structure 9 + 0 in an ICC is demonstrated for the first time. In conclusion, we report positive staining c-kit, CD34, nestin and Ki 67. ICCs fulfilled the usual transmission electron microscopy (TEM) criteria. A new ultrastructural characteristic of at least some ICCs is demonstrated: the presence of a single cilium. Some populations of ICCs in the rabbit duodenum present certain immunohistochemical and ultrastructural characteristics that often are present in progenitor cells. PMID:17760839

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM

PubMed Central

Bi, P.; Kuang, S.

2012-01-01

Stem cell niche plays a critical role in regulating the behavior and function of adult stem cells that underlie tissue growth, maintenance, and regeneration. In the skeletal muscle, stem cells, called satellite cells, contribute to postnatal muscle growth and hypertrophy, and thus, meat production in agricultural animals. Satellite cells are located adjacent to mature muscle fibers underneath a sheath of basal lamina. Microenvironmental signals from extracellular matrix mediated by the basal lamina and from the host myofiber both impinge on satellite cells to regulate their activity. Furthermore, several types of muscle interstitial cells, including intramuscular preadipocytes and connective tissue fibroblasts, have recently been shown to interact with satellite cells and actively regulate the growth and regeneration of postnatal skeletal muscles. From this regard, interstitial adipogenic cells are not only important for marbling and meat quality, but also represent an additional cellular component of the satellite cell niche. At the molecular level, these interstitial cells may interact with satellite cells through cell surface ligands, such as delta-like 1 homolog (Dlk1) protein whose overexpression is thought to be responsible for muscle hypertrophy in callipyge sheep. In fact, extracellular Dlk1 protein has been shown to promote the myogenic differentiation of satellite cells. Understanding the cellular and molecular mechanisms within the stem cell niche that regulate satellite cell differentiation and maintain muscle homeostasis may lead to promising approaches to optimizing muscle growth and composition, thus improving meat production and quality. PMID:22100594

Mechanics of Fluid-Filled Interstitial Gaps. I. Modeling Gaps in a Compact Tissue.

PubMed

Parent, Serge E; Barua, Debanjan; Winklbauer, Rudolf

2017-08-22

Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Thermal effects in tissues induced by interstitial irradiation of near infrared laser with a cylindrical diffuser

NASA Astrophysics Data System (ADS)

Le, Kelvin; Johsi, Chet; Figueroa, Daniel; Goddard, Jessica; Li, Xiaosong; Towner, Rheal A.; Saunders, Debra; Smith, Nataliya; Liu, Hong; Hode, Tomas; Nordquist, Robert E.; Chen, Wei R.

2011-03-01

Laser immunotherapy (LIT), using non-invasive laser irradiation, has resulted in promising outcomes in the treatment of late-stage cancer patients. However, the tissue absorption of laser light limits the clinical applications of LIT in patients with dark skin, or with deep tumors. The present study is designed to investigate the thermal effects of interstitial irradiation using an 805-nm laser with a cylindrical diffuser, in order to overcome the limitations of the non-invasive mode of treatment. Cow liver and rat tumors were irradiated using interstitial fiber. The temperature increase was monitored by thermocouples that were inserted into the tissue at different sites around the cylinder fiber. Three-dimensional temperature distribution in target tissues during and after interstitial laser irradiation was also determined by Proton Resonance Frequency. The preliminary results showed that the output power of laser and the optical parameters of the target tissue determined the light distribution in the tissue. The temperature distributions varied in the tissue according to the locations relative to the active tip of the cylindrical diffuser. The temperature increase is strongly related to the laser power and irradiation time. Our results using thermocouples and optical sensors indicated that the PRF method is reliable and accurate for temperature determination. Although the inhomogeneous biological tissues could result in temperature fluctuation, the temperature trend still can be reliable enough for the guidance of interstitial irradiation. While this study provides temperature profiles in tumor tissue during interstitial irradiation, the biological effects of the irradiation remain unclear. Future studies will be needed, particularly in combination with the application of immunostimulant for inducing tumor-specific immune responses in the treatment of metastatic tumors.

Severe respiratory failure as a presenting feature of an interstitial lung disease associated with anti-synthetase syndrome (ASS).

PubMed

Piroddi, Ines Maria Grazia; Ferraioli, Gianluca; Barlascini, Cornelius; Castagneto, Corrado; Nicolini, Antonello

2016-07-01

Anti-synthetase syndrome (ASS) is defined as a heterogeneous connective tissue disorder characterized by the association of an interstitial lung disease (ILD) with or without inflammatory myositis with the presence of anti-aminoacyl-tRNA-synthetase antibodies. ILD is one of the major extra-muscular manifestations of polymyositis and dermatomyositis. We report a case of a patient with dyspnea, cough, and intermittent fever as well as ILD associated ASS in the absence of muscular involvement. This patient was admitted to the emergency department with severe respiratory failure requiring non-invasive ventilation. Our patient's case demonstrates that the diagnosis of ASS may not be obvious. However, its diagnosis leads to appropriate and potentially life-saving treatment. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Effects of rituximab in connective tissue disorders related interstitial lung disease.

PubMed

Lepri, Gemma; Avouac, Jerome; Airò, Paolo; Anguita Santos, Francisco; Bellando-Randone, Silvia; Blagojevic, Jelena; Garcia Hernàndez, Francisco; Gonzalez Nieto, Jose Antonio; Guiducci, Serena; Jordan, Suzana; Limaye, Vidya; Maurer, Britta; Selva-O'Callaghan, Albert; Riccieri, Valeria; Distler, Oliver; Matucci-Cerinic, Marco; Allanore, Yannick

2016-01-01

Interstitial lung disease (ILD) is a key prognostic factor in connective tissue disorders (CTDs). The aim of our study was to assess the changes in pulmonary functional tests (PFTs) in various CTDs, including anti-synthetase syndrome (SYN), systemic sclerosis (SSc) and mixed connective tissue disorder (MCTD), following the use of rituximab therapy. A multicentre retrospective analysis of patients with ILD secondary to SYN (n=15), MCTD (n=6) and SSc (n=23). PFTs were performed at baseline and at 1 and 2 years of follow-up. The primary outcome was the change in forced vital capacity (FVC) at 1 year. In the SYN population, median FVC changed from 53.0% (42.0-90.0) at baseline to 51.4% (45.6-85.0) at 1 year and 63.0 (50-88) (p=0.6) at 2 years (p=0.14). In SSc, FVC changed from 81.0% (66.0-104.0) at baseline to 89.0% (65.0-113.0) at 1 year (p=0.1) and 74.5 (50-91) at 2 years (p=0.07). In the MCTD population, FVC changed from 64.5% (63.0-68.0) at baseline to 63.0% (59.0-71.0) at 1 year (p=0.6) and 61 (59-71) after 2 years (p=0.8). DLCO showed a trend for improvement in the SYN population (p=0.06 at 1 year and 0.2 at years) while changes remain non-significant in the SSc and MCTD patients. In SYN patients, the percentage of responders at 1 year for FVC (33.3%) was greater than in SSc (9.5%) (p=0.07) and MCTD (17%) (p=0.45). RTX showed a satisfactory safety profile. A trend of improvement of PFTs was observed in SYN patients although not reaching significance, while SSc and MCTD patients were stabilised.

Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

PubMed

O'Dwyer, David N; Armstrong, Michelle E; Cooke, Gordon; Dodd, Jonathan D; Veale, Douglas J; Donnelly, Seamas C

2013-10-01

Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD. © 2013.

Expression of bone morphogenetic proteins 4, 6 and 7 is downregulated in kidney allografts with interstitial fibrosis and tubular atrophy.

PubMed

Furic-Cunko, Vesna; Kes, Petar; Coric, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Basic-Jukic, Nikolina

2015-07-01

Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This paper investigates the connection between the expression pattern of BMPs in kidney allograft tissue versus the cause of allograft dysfunction. The expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained by transplant nephrectomy is investigated. Immunohistochemical staining is semiquantitatively evaluated for intensity to identify the expression pattern of BMPs in normal and allograft kidney tissues. The expression of BMP4 is unique between different tubular cell types in grafts without signs of fibrosis. This effect is not found in specimens with high grades of interstitial fibrosis and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7 expression is reduced in a significant fraction of specimens relative to those without signs of IFTA. The expression pattern of BMP6 indicates that its activation may be triggered by the act of transplantation and subsequent reperfusion injury. The expression of BMP2 is strong in all types of tubular epithelial cells and does not differ between the compared allografts and control kidney specimens. The intensity and expression pattern of BMP4, BMP6 and BMP7 in transplanted kidney tissue are found to be dependent upon the length of the transplanted period, the clinical indication for transplant nephrectomy and signs of IFTA in kidney tissue.

Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

PubMed

Saunders, Peter; Tsipouri, Vicky; Keir, Gregory J; Ashby, Deborah; Flather, Marcus D; Parfrey, Helen; Babalis, Daphne; Renzoni, Elisabetta A; Denton, Christopher P; Wells, Athol U; Maher, Toby M

2017-06-15

Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population. RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m 2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24 weeks. Key secondary endpoints include: safety, change in FVC at 48 weeks as well as survival, change in oxygen requirements, total 48-week corticosteroid exposure and utilisation of health care resources. This is the first randomised control trial to study the efficacy of rituximab as first-line treatment in CTD-associated ILD. The results generated should provide important information on the treatment of a life-threatening complication affecting a rare group of CTDs. ClinicalTrials.gov, NCT01862926. Registered on 22 May 2013.

Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive

PubMed Central

Newton, Chad A.; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S.; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R.; Garcia, Christine Kim

2017-01-01

Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals. 115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed. Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year−1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis. Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. PMID:27540018

Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

PubMed

Newton, Chad A; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R; Garcia, Christine Kim

2016-12-01

Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed.Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year -1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis.Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. Copyright ©ERS 2016.

Proteomics detection of S100A6 in tumor tissue interstitial fluid and evaluation of its potential as a biomarker of cholangiocarcinoma.

PubMed

Onsurathum, Sudarat; Haonon, Ornuma; Pinlaor, Porntip; Pairojkul, Chawalit; Khuntikeo, Narong; Thanan, Raynoo; Roytrakul, Sittiruk; Pinlaor, Somchai

2018-04-01

Tumor interstitial fluid contains tumor-specific proteins that may be useful biomarkers for cancers. In this study, we identified proteins present in cholangiocarcinoma interstitial fluid. Proteins derived from three samples of tumor interstitial fluid and paired samples of adjacent normal interstitial fluid from cholangiocarcinoma patients were subjected to two-dimensional liquid chromatography with tandem mass spectrometry. Candidate proteins were selected based on a greater than twofold change in expression levels between tumor interstitial fluid and normal interstitial fluid. Upregulation of six proteins in tumor interstitial fluid, including S100 calcium binding protein A6 (S100A6), S100 calcium binding protein A9, aldo-keto reductase family 1 member C4, neuropilin-1, 14-3-3 zeta/delta, and triosephosphate isomerase was assessed by western blot and immunohistochemistry. Their potential as markers was evaluated in human cholangiocarcinoma tissue arrays, and in serum using enzyme-linked immunosorbent assay. Expression of S100A6 was higher in tumor interstitial fluid than in normal interstitial fluid and showed the highest positive rate (98.96%) in cholangiocarcinoma tissues. Serum levels of S100A6 did not differ between cholangitis and cholangiocarcinoma patients, but were significantly higher than in healthy individuals ( p < 0.0001). In cholangiocarcinoma cases, S100A6 level was associated with vascular invasion ( p = 0.007) and could distinguish cholangiocarcinoma patients from healthy individuals as effectively as the carbohydrate antigen 19-9. In addition, potential for drug treatment targeting S100A6 and other candidate proteins was also demonstrated using STITCH analysis. In conclusion, proteomics analysis of tumor interstitial fluid could be a new approach for biomarker discovery, and S100A6 is a potential risk marker for screening of cholangiocarcinoma.

Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease.

PubMed

Porcher, Christophe; Baldo, Marjolaine; Henry, Monique; Orsoni, Pierre; Julé, Yvon; Ward, Sean M

2002-01-01

Interstitial cells of Cajal are critical for the generation of electrical slow waves that regulate the phasic contractile activity of the tunica muscularis of the GI tract. Under certain pathophysiological conditions loss of interstitial cells of Cajal may play a role in the generation of certain motility disorders. The aim of the present study was to determine if there is an abnormality in the density or distribution of interstitial cells of Cajal from patients with Crohn's disease. Small intestines from control subjects and patients with Crohn's disease were examined using immunohistochemistry and antibodies against the Kit receptor, which is expressed in interstitial cells of Cajal within the tunica muscularis of the GI tract. The density and distribution of interstitial cells of Cajal were assessed in the longitudinal and circular muscle layers and in the myenteric and deep muscular plexus regions of Crohn's and control tissues. Tissues from Crohn's disease patients showed an almost complete abolition of interstitial cells of Cajal within the longitudinal and circular muscle layers and a significant reduction in numbers at the level of the myenteric and deep muscular plexuses. In tissues from Crohn's disease patients, the density of interstitial cells of Cajal was reduced throughout the tunica muscularis in comparison to control small intestines. The disturbance of intestinal motility that occurs in patients with Crohn's disease may be a consequence of the loss of or defects in specific populations of interstitial cells of Cajal within the tunica muscularis.

Interstitial hydraulic conductivity and interstitial fluid pressure for avascular or poorly vascularized tumors.

PubMed

Liu, L J; Schlesinger, M

2015-09-07

A correct description of the hydraulic conductivity is essential for determining the actual tumor interstitial fluid pressure (TIFP) distribution. Traditionally, it has been assumed that the hydraulic conductivities both in a tumor and normal tissue are constant, and that a tumor has a much larger interstitial hydraulic conductivity than normal tissue. The abrupt transition of the hydraulic conductivity at the tumor surface leads to non-physical results (the hydraulic conductivity and the slope of the TIFP are not continuous at tumor surface). For the sake of simplicity and the need to represent reality, we focus our analysis on avascular or poorly vascularized tumors, which have a necrosis that is mostly in the center and vascularization that is mostly on the periphery. We suggest that there is an intermediary region between the tumor surface and normal tissue. Through this region, the interstitium (including the structure and composition of solid components and interstitial fluid) transitions from tumor to normal tissue. This process also causes the hydraulic conductivity to do the same. We introduce a continuous variation of the hydraulic conductivity, and show that the interstitial hydraulic conductivity in the intermediary region should be monotonically increasing up to the value of hydraulic conductivity in the normal tissue in order for the model to correspond to the actual TIFP distribution. The value of the hydraulic conductivity at the tumor surface should be the lowest in value. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanics of interstitial-lymphatic fluid transport: theoretical foundation and experimental validation.

PubMed

Swartz, M A; Kaipainen, A; Netti, P A; Brekken, C; Boucher, Y; Grodzinsky, A J; Jain, R K

1999-12-01

Interstitial fluid movement is intrinsically linked to lymphatic drainage. However, their relationship is poorly understood, and associated pathologies are mostly untreatable. In this work we test the hypothesis that bulk tissue fluid movement can be evaluated in situ and described by a linear biphasic theory which integrates the regulatory function of the lymphatics with the mechanical stresses of the tissue. To accomplish this, we develop a novel experimental and theoretical model using the skin of the mouse tail. We then use the model to demonstrate how interstitial-lymphatic fluid movement depends on a balance between the elasticity, hydraulic conductivity, and lymphatic conductance as well as to demonstrate how chronic swelling (edema) alters the equipoise between tissue fluid balance parameters. Specifically, tissue fluid equilibrium is perturbed with a continuous interstitial infusion of saline into the tip of the tail. The resulting gradients in tissue stress are measured in terms of interstitial fluid pressure using a servo-null system. These measurements are then fit to the theory to provide in vivo estimates of the tissue hydraulic conductivity, elastic modulus, and overall resistance to lymphatic drainage. Additional experiments are performed on edematous tails to show that although chronic swelling causes an increase in the hydraulic conductivity, its greatly increased distensibility (due to matrix remodeling) dampens the driving forces for fluid movement and leads to fluid stagnation. This model is useful for examining potential treatments for edema and lymphatic disorders as well as substances which may alter tissue fluid balance and/or lymphatic drainage.

Assessment of thermal effects of interstitial laser phototherapy on mammary tumors using proton resonance frequency method

PubMed Central

Le, Kelvin; Li, Xiaosong; Figueroa, Daniel; Towner, Rheal A.; Garteiser, Philippe; Saunders, Debra; Smith, Nataliya; Liu, Hong; Hode, Tomas; Nordquist, Robert E.; Chen, Wei R.

2011-01-01

Laser immunotherapy (LIT) uses a synergistic approach to treat cancer systemically through local laser irradiation and immunological stimulation. Currently, LIT utilizes dye-assisted noninvasive laser irradiation to achieve selective photothermal interaction. However, LIT faces difficulties treating deeper tumors or tumors with heavily pigmented overlying skin. To circumvent these barriers, we use interstitial laser irradiation to induce the desired photothermal effects. The purpose of this study is to analyze the thermal effects of interstitial irradiation using proton resonance frequency (PRF). An 805-nm near-infrared laser with an interstitial cylindrical diffuser was used to treat rat mammary tumors. Different power settings (1.0, 1.25, and 1.5 W) were applied with an irradiation duration of 10 min. The temperature distributions of the treated tumors were measured by a 7 T magnetic resonance imager using PRF. We found that temperature distributions in tissue depended on both laser power and time settings, and that variance in tissue composition has a major influence in temperature elevation. The temperature elevations measured during interstitial laser irradiation by PRF and thermocouple were consistent, with some variations due to tissue composition and the positioning of the thermocouple's needle probes. Our results indicated that, for a tissue irradiation of 10 min, the elevation of rat tumor temperature ranged from 8 to 11°C for 1 W and 8 to 15°C for 1.5 W. This is the first time a 7 T magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. Our work provides a basic understanding of the photothermal interaction needed to control the thermal damage inside a tumor using interstitial laser treatment. Our work may lead to an optimal protocol for future cancer treatment using interstitial phototherapy in conjunction with immunotherapy. PMID:22191937

Pulmonary hypertension in patients with interstitial lung disease.

PubMed

Karampitsakos, Theodoros; Tzouvelekis, Argyrios; Chrysikos, Serafeim; Bouros, Demosthenes; Tsangaris, Iraklis; Fares, Wassim H

2018-06-01

Interstitial lung diseases (ILDs) comprise a broad and heterogeneous group of more than two hundred diseases with common functional characteristics. Their diagnosis and management require a multidisciplinary approach. This multidisciplinary approach involves the assessment of comorbid conditions including pulmonary hypertension (PH) that exerts a dramatic impact on survival. The current World Health Organization (WHO) classification of PH encompasses many of the interstitial lung diseases into WHO Group 3, while sarcoidosis, Pulmonary Langerhans Cell Histiocytosis and lymphangioleiomyomatosis are placed into WHO Group 5 as diseases with unclear or multifactorial mechanisms. Connective tissue diseases could span any of the 5 WHO groups based on the primary phenotype into which they manifest. Interestingly, several challenging phenotypes present with features that overlap between two or more WHO PH groups. Currently, PH-specific treatment is recommended only for patients classified into WHO Group 1 PH. The lack of specific treatment for other groups, including PH in the setting of ILD, reflects the poor outcomes of these patients. Thus, identification of the optimal strategy for ILD patients with PH remains an amenable need. This review article provides a brief overview of biomarkers indicative of vascular remodeling in interstitial lung disease, summarizes the current state of knowledge regarding patients with PH and ILD and highlights future perspectives that remain to be addressed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prediction of oxygen distribution in aortic valve leaflet considering diffusion and convection.

PubMed

Wang, Ling; Korossis, Sotirios; Fisher, John; Ingham, Eileen; Jin, Zhongmin

2011-07-01

Oxygen supply and transport is an important consideration in the development of tissue engineered constructs. Previous studies from our group have focused on the effect of tissue thickness on the oxygen diffusion within a three-dimensional aortic valve leaflet model, and highlighted the necessity for additional transport mechanisms such as oxygen convection. The aims of this study were to investigate the effect of interstitial fluid flow within the aortic valve leaflet, induced by the cyclic loading of the leaflet, on oxygen transport. Indentation testing and finite element modelings were employed to derive the biphasic properties of the leaflet tissue. The biphasic properties were subsequently used in the computational modeling of oxygen convection in the leaflet, which was based on the effective interstitial fluid velocity and the tissue deformation. Subsequently, the oxygen profile was predicted within the valve leaflet model by solving the diffusion and convection equation simultaneously utilizing the finite difference method. The compression modulus (E) and hydraulic permeability were determined by adapting a finite element model to the experimental indentation test on valvular tissue, E = 0.05MPa, and k =2.0 mm4/Ns. Finite element model of oxygen convection in valvular tissue incorporating the predicted biphasic properties was developed and the interstitial fluid flow rate was calculated falling in range of 0.025-0.25 mm/s depending on the tissue depth. Oxygen distribution within valvular tissue was predicted using one-dimensional oxygen diffusion model taking into consider the interstitial fluid effect. It was found that convection did enhance the oxygen transport in valvular tissue by up to 68% increase in the minimum oxygen tension within the tissue, depending on the strain level of the tissue as reaction of the magnitude and frequencies of the cardiac loading. The effective interstitial fluid velocity was found to play an important role in enhancing the oxygen transport within the valve leaflet. Such an understanding is important in the development of valvular tissue engineered constructs.

Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF).

PubMed

Gromov, Pavel; Gromova, Irina

2016-01-01

Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue.

Effect of α-trinositol on interstitial fluid pressure, oedema generation and albumin extravasation in experimental frostbite in the rat

PubMed Central

Berg, A; Aas, P; Gustafsson, T; Reed, R K

1999-01-01

The anti-inflammatory effect of α-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. α-Trinositol (40 mg kg body weight−1) was administered intravenously as a bolus both before and/or in the interval between freezing and thawing of the tissue. Pif was measured in rat paw skin with micropipettes connected to a servo-controlled counterpressure system. Oedema formation was estimated by measuring the increase in total tissue water content (wet weight minus dry weight divided by dry weight). Albumin extravasation (i.e., the difference between the plasma equivalent space for 125I- and 131I-human serum albumin (HSA) circulating for different time intervals) was used to estimate the microvascular leakage. Compared to untreated animals, α-trinositol given pre- and/or post-freeze reduced total tissue water and albumin extravasation as well as the fall in Pif in injured tissue significantly (P<0.05). α-Trinositol given only post-freeze reduced total tissue water and albumin extravasation from 4.46±0.93 and 2.37±1.12 to 2.51±0.29 and 0.36±0.18 ml g dry weight−1, respectively (P<0.05). Pif fell from −0.8±0.2 mmHg pre-freeze to −3.4±1.0 mmHg (P<0.05) at 20 min after tissue injury (circulatory arrest) and was attenuated by treatment with α-trinositol. We conclude that α-trinositol exerts its anti-oedematous effect by acting on the extracellular matrix, attenuating the lowering of Pif as well as on the microvascular wall, thereby decreasing the protein extravasation. PMID:10217530

In vivo interstitial glucose characterization and monitoring in the skin by ATR-FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Skrebova Eikje, Natalja

2011-03-01

Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related 1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise measurements of interstitial glucose levels may be more important clinically.

CHANGES IN LUNG PARENCHYMA WITH PREOPERATIVE Co$sup 60$-IRRADIATION OF BRONCHIAL CARCINOMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widow, W.

1959-01-01

Histologic studies were made of resected lung tissue of 24 patients subjected to radiotherapy. Radiation pneumonitis with incipient fibrosis was observed in 14 cases. In only five of these cases could the histologic findings be confirmed radiologically. The histologic changes included swelling of alveolar septa, interstitial edema, increase of connective tissue components, giant cell formation, exfoliation of alveolar cells, intra-alveolar edema, depositio of cellular debris in small bronchi with apparent injury to the ciliated epithelial and mucous cells, and swelling of the peribronchial and perivascular tissue and pleura. Only a sparse inflammatory cell infiltrate was noted. These responses could notmore » be closely correlated with the radiation dose. The radiation reaction was most marked in the vicinity of old tuberculous lesions. No permanent impairment of pulmonary function would be expected from the observed histologic changes. (H.H.D.)« less

Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris.

PubMed

Duchemann, Boris; Annesi-Maesano, Isabella; Jacobe de Naurois, Camille; Sanyal, Shreosi; Brillet, Pierre-Yves; Brauner, Michel; Kambouchner, Marianne; Huynh, Sophie; Naccache, Jean Marc; Borie, Raphael; Piquet, Jacques; Mekinian, Arsène; Virally, Jerôme; Uzunhan, Yurdagul; Cadranel, Jacques; Crestani, Bruno; Fain, Olivier; Lhote, Francois; Dhote, Robin; Saidenberg-Kermanac'h, Nathalie; Rosental, Paul-André; Valeyre, Dominique; Nunes, Hilario

2017-08-01

The objective of the study was to estimate the prevalence and incidence of interstitial lung diseases (ILDs) in Seine-Saint-Denis, a multi-ethnic county of Greater Paris, France.Patients with ILDs were identified between January and December 2012 by using several sources; all potentially involved medical specialists from public and private hospitals, community-based pulmonologists and general practitioners, and the Social Security system. Diagnoses were validated centrally by an expert multidisciplinary discussion.1170 ILD cases were reported (crude overall prevalence: 97.9/10 5 and incidence: 19.4/10 5 /year). In the 848 reviewed cases, the most prevalent diagnoses were sarcoidosis (42.6%), connective tissue diseases associated ILDs (CTDs-ILDs) (16%), idiopathic pulmonary fibrosis (IPF) (11.6%), and occupational ILDs (5.0%), which corresponded to a crude prevalence of 30.2/10 5 for sarcoidosis, 12.1/10 5 for CTDs-ILDs and 8.2/10 5 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/10 5 An adjusted multinomial model demonstrated an increased risk of sarcoidosis in North Africans and Afro-Caribbeans and of CTDs-ILDs in Afro-Caribbeans, compared to that in Europeans.This study, with a comprehensive recruitment and stringent diagnostic criteria, emphasises the importance of secondary ILDs, particularly CTDs-ILDs and the relatively low prevalence of IPF, and confirms that sarcoidosis is a rare disease in France. Copyright ©ERS 2017.

First reported association of chronic lymphocytic leukaemia and interstitial granulomatous dermatitis.

PubMed

Riaz, Irbaz Bin; Kamal, Muhammad Umar; Segal, Robert J; Anwer, Faiz

2016-05-18

Interstitial granulomatous dermatitis (IGD), a rare disease, is well known to be associated with connective tissue disorders, malignancies and several drugs. We describe this first case of IGD in association with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). A 66-year-old woman with a 6-year history of untreated CLL/SLL, presented with a 2-month history of progressively worsening eruption of the left thigh, along with fatigue, lymphadenopathy and night sweats. Skin biopsy showed findings consistent with IGD and infiltration of CLL. The eruption was non-responsive to treatment with antibiotics and local steroids. There was a significant improvement in the rash after an initial cycle of chemotherapy (combination therapy with bendamustine and rituximab) and complete resolution by the third cycle, for the treatment of her CLL. We suggest that the possibility of an underlying haematological malignancy should be investigated in patients with a skin rash non-responsive to conventional therapy. 2016 BMJ Publishing Group Ltd.

Chromium mapping in male mice reproductive glands exposed to CrCl 3 using proton and X-ray synchrotron radiation microbeams

NASA Astrophysics Data System (ADS)

Ortega, R.; Devès, G.; Bonnin-Mosbah, M.; Salomé, M.; Susini, J.; Anderson, L. M.; Kasprzak, K. S.

2001-07-01

Preconception exposure to certain chemicals may increase risk of tumors in offspring, especially with regard to occupational metals such as chromium. However, the mechanism of chromium trans-generation carcinogenicity remains unknown. Using scanning proton X-ray microanalysis we have been able to detect chromium in testicular tissue sections from mice treated by intraperitoneal injection of 1 mmol/kg CrCl 3. Chromium concentration was about 5 μg/g dry mass in average, but higher concentrations were found within the limiting membrane of the testes, the tunica albuginea. In addition, synchrotron radiation X-ray fluorescence measurements, with microscopic resolution, clearly demonstrated the presence of chromium in the tunica albuginea but also within isolated cells from the interstitial connective tissue.

Smoking-related interstitial lung diseases.

PubMed

Caminati, A; Graziano, P; Sverzellati, N; Harari, S

2010-12-01

In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

Influence of gravity for optimal head positions in the treatment of head injury patients.

PubMed

Li, Xiaogai; von Holst, Hans; Kleiven, Svein

2011-10-01

Brain edema is a major neurological complication of traumatic brain injury (TBI), commonly including a pathologically increased intracranial pressure (ICP) associated with poor outcome. In this study, gravitational force is suggested to have a significant impact on the pressure of the edema zone in the brain tissue and the objective of the study was to investigate the significance of head position on edema at the posterior part of the brain using a finite element (FE) model. A detailed FE model including the meninges, brain tissue and a fully connected cerebrospinal fluid (CSF) system was used in this study. Brain tissue was modelled as a poroelastic material consisting of an elastic solid skeleton composed of neurons and neuroglia, permeated by interstitial fluid. The effect of head positions (supine and prone position) due to gravity was investigated for a localized brain edema at the posterior part of the brain. The water content increment at the edema zone remained nearly identical for both positions. However, the interstitial fluid pressure (IFP) inside the edema zone decreased around 15% by having the head in a prone position compared with a supine position. The decrease of IFP inside the edema zone by changing patient position from supine to prone has the potential to alleviate the damage to central nervous system nerves. These observations indicate that considering the patient's head position during intensive care and at rehabilitation might be of importance to the treatment of edematous regions in TBI patients.

X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression.

PubMed

Benali, S L; Lees, G E; Nabity, M B; Aricò, A; Drigo, M; Gallo, E; Giantin, M; Aresu, L

2016-07-01

X-linked hereditary nephropathy (XLHN) in Navasota dogs is a spontaneously occurring disease caused by a mutation resulting in defective production of type IV collagen and juvenile-onset renal failure. The study was aimed at examining the evolution of renal damage and the expression of selected molecules potentially involved in the pathogenesis of XLHN. Clinical data and renal samples were obtained in 10 XLHN male dogs and 5 controls at 4 (T0), 6 (T1), and 9 (T2) months of age. Glomerular and tubulointerstitial lesions were scored by light microscopy, and the expression of 21 molecules was investigated by quantitative real-time polymerase chain reaction with selected proteins evaluated by immunohistochemistry. No significant histologic lesions or clinicopathologic abnormalities were identified in controls at any time-point. XLHN dogs had progressive proteinuria starting at T0. At T1, XLHN dogs had a mesangioproliferative glomerulopathy with glomerular loss, tubular necrosis, and interstitial fibrosis. At T2, glomerular and tubulointerstitial lesions were more severe, particularly glomerular loss, interstitial fibrosis, and inflammation. At T0, transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α mRNA were overexpressed in XLHN dogs compared with controls. Clusterin and TIMP1 transcripts were upregulated in later stages of the disease. Transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α should be considered as key players in the initial events of XHLN. Clusterin and TIMP1 appear to be more associated with the progression rather than initiation of tubulointerstitial damage in chronic renal disease. © The Author(s) 2016.

Differences in clinical Pneumocystis pneumonia in rheumatoid arthritis and other connective tissue diseases suggesting a rheumatoid-specific interstitial lung injury spectrum.

PubMed

Shimada, Kota; Yokosuka, Kyoko; Nunokawa, Takahiro; Sugii, Shoji

2018-06-06

To compare Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA) with PCP in patients with non-RA connective tissue diseases (CTDs) in order to clarify the characteristics of the former. We extracted consecutive patients satisfying the following criteria for "clinical PCP": (1) positive plasma β-D-glucan, (2) PCP-compatible computed tomography findings of the lung, and (3) successful treatment with antipneumocystic antibiotics. Patients who underwent methylprednisolone "pulse" therapy or sufficient antibiotics to cure bacterial pneumonia were excluded. We used the t test, U test, or Fischer's exact probability test to compare the two groups and Jonckheere-Terpstra's test and Ryan's procedure for the trend test. Thirty-five cases were extracted. The underlying rheumatic diseases were RA in 25 and non-RA CTDs in ten. At the onset of clinical PCP, the lymphocyte counts were 884 vs 357/mm 3 (p < 0.001), PC-PCR positivity 64% vs 100% (p = 0.029), glucocorticoid dose 4.0 vs 17.5 mg PSL/day (p < 0.001), and methotrexate dose 8 vs 0 mg/week (p = 0.003). The PC-PCR-negative patients, observed only in the RA group, were all receiving methotrexate (MTX) therapy except one patient who was receiving high-dose prednisolone alone. All PC-PCR-positive patients were receiving glucocorticoid, TNF inhibitor, or a non-MTX immunosuppressant. No patient with MTX alone had positive PC-PCR results. Clinical PCP in RA patients differed from that in non-RA CTD patients and may be understood as only a part of the rheumatoid-specific interstitial lung injury spectrum influenced by multiple, synergistic factors including MTX, Pneumocystis, and RA itself.

T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning

PubMed Central

Gaylo, Alison; Schrock, Dillon C.; Fernandes, Ninoshka R. J.; Fowell, Deborah J.

2016-01-01

Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell’s antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function. PMID:27790220

T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning.

PubMed

Gaylo, Alison; Schrock, Dillon C; Fernandes, Ninoshka R J; Fowell, Deborah J

2016-01-01

Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell's antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function.

Photoacoustic-based sO2 estimation through excised bovine prostate tissue with interstitial light delivery.

PubMed

Mitcham, Trevor; Taghavi, Houra; Long, James; Wood, Cayla; Fuentes, David; Stefan, Wolfgang; Ward, John; Bouchard, Richard

2017-09-01

Photoacoustic (PA) imaging is capable of probing blood oxygen saturation (sO 2 ), which has been shown to correlate with tissue hypoxia, a promising cancer biomarker. However, wavelength-dependent local fluence changes can compromise sO 2 estimation accuracy in tissue. This work investigates using PA imaging with interstitial irradiation and local fluence correction to assess precision and accuracy of sO 2 estimation of blood samples through ex vivo bovine prostate tissue ranging from 14% to 100% sO 2 . Study results for bovine blood samples at distances up to 20 mm from the irradiation source show that local fluence correction improved average sO 2 estimation error from 16.8% to 3.2% and maintained an average precision of 2.3% when compared to matched CO-oximeter sO 2 measurements. This work demonstrates the potential for future clinical translation of using fluence-corrected and interstitially driven PA imaging to accurately and precisely assess sO 2 at depth in tissue with high resolution.

Characterization of the Chicken Ovarian Cancer Model

DTIC Science & Technology

2005-08-01

Typical staining of tumor in an area of stromal hyperplasia . Figure 5. Adenocarcinoma, Ovary, Chicken, Her2/neu. Intense staining of tumor cells in...variable amounts of interstitial fibrovascular tissue and/or smooth muscle bundles, which accounted for their scirrhous nature grossly. 22...Figure 25). Figure 25. Peritoneum, Adenocarcinoma. Interstitial fibrovascular tissue and/or smooth muscle bundles account for the scirrhous

Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

PubMed

Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A

2018-05-15

To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Physiological water model development

NASA Technical Reports Server (NTRS)

Doty, Susan

1993-01-01

The water of the human body can be categorized as existing in two main compartments: intracellular water and extracellular water. The intracellular water consists of all the water within the cells and constitutes over half of the total body water. Since red blood cells are surrounded by plasma, and all other cells are surrounded by interstitial fluid, the intracellular compartment has been subdivided to represent these two cell types. The extracellular water, which includes all of the fluid outside of the cells, can be further subdivided into compartments which represent the interstitial fluid, circulating blood plasma, lymph, and transcellular water. The interstitial fluid surrounds cells outside of the vascular system whereas plasma is contained within the blood vessels. Avascular tissues such as dense connective tissue and cartilage contain interstitial water which slowly equilibrates with tracers used to determine extracellular fluid volume. For this reason, additional compartments are sometimes used to represent these avascular tissues. The average size of each compartment, in terms of percent body weight, has been determined for adult males and females. These compartments and the forces which cause flow between them are presented. The kidneys, a main compartment, receive about 25 percent of the cardiac output and filters out a fluid similar to plasma. The composition of this filtered fluid changes as it flows through the kidney tubules since compounds are continually being secreted and reabsorbed. Through this mechanism, the kidneys eliminate wastes while conserving body water, electrolytes, and metabolites. Since sodium accounts for over 90 percent of the cations in the extracellular fluid, and the number of cations is balanced by the number of anions, considering the renal handling sodium and water only should sufficiently describe the relationship between the plasma compartment and kidneys. A kidney function model is presented which has been adapted from a previous model of normal renal function in man. To test the validity of the proposed kidney model, results predicted by the model will be compared to actual data involving injected or ingested fluids and subsequent urine flow rates. Comparison of the model simulation to actual data following the ingestion of 1 liter of water is shown. The model simulation is also shown with actual data following the intravenous infusion of hypertonic saline.

A review of recent advances in the assessment of bone porosity, permeability, and interstitial fluid flow

PubMed Central

Cardoso, Luis; Fritton, Susannah P.; Gailani, Gaffar; Benalla, Mohammed; Cowin, Stephen C.

2012-01-01

This contribution reviews recent research performed to assess the porosity and permeability of bone tissue with the objective of understanding interstitial fluid movement. Bone tissue mechanotransduction is considered to occur due to the passage of interstitial pore fluid adjacent to dendritic cell structures in the lacunar-canalicular porosity. The movement of interstitial fluid is also necessary for the nutrition of osteocytes. This review will focus on four topics related to improved assessment of bone interstitial fluid flow. First, the advantages and limitations of imaging technologies to visualize bone porosities and architecture at several length scales are summarized. Second, recent efforts to measure the vascular porosity and lacunar-canalicular microarchitecture are discussed. Third, studies associated with the measurement and estimation of the fluid pressure and permeability in the vascular and lacunar-canalicular domains are summarized. Fourth, the development of recent models to represent the interchange of fluids between the bone porosities is described. PMID:23174418

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

PubMed Central

Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

2015-01-01

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150

Automated quantification of renal interstitial fibrosis for computer-aided diagnosis: A comprehensive tissue structure segmentation method.

PubMed

Tey, Wei Keat; Kuang, Ye Chow; Ooi, Melanie Po-Leen; Khoo, Joon Joon

2018-03-01

Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses. This study proposes an automated quantification system for measuring the amount of interstitial fibrosis in renal biopsy images as a consistent basis of comparison among pathologists. The system extracts and segments the renal tissue structures based on colour information and structural assumptions of the tissue structures. The regions in the biopsy representing the interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area and quantified as a percentage of the total area of the biopsy sample. A ground truth image dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated a good correlation in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses due to the uncertainties in human judgement. An automated quantification system for accurately measuring the amount of interstitial fibrosis in renal biopsy images is presented as a consistent basis of comparison among pathologists. The system identifies the renal tissue structures through knowledge-based rules employing colour space transformations and structural features extraction from the images. In particular, the renal glomerulus identification is based on a multiscale textural feature analysis and a support vector machine. The regions in the biopsy representing interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area. The experiments conducted evaluate the system in terms of quantification accuracy, intra- and inter-observer variability in visual quantification by pathologists, and the effect introduced by the automated quantification system on the pathologists' diagnosis. A 40-image ground truth dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated an average error of 9 percentage points in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists involving samples from 70 kidney patients also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. The accuracy of the proposed quantification system has been validated with the ground truth dataset and compared against the pathologists' quantification results. It has been shown that the correlation between different pathologists' estimation of interstitial fibrosis area has significantly improved, demonstrating the effectiveness of the quantification system as a diagnostic aide. Copyright © 2017 Elsevier B.V. All rights reserved.

A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis

PubMed Central

Manetti, Mirko; Rosa, Irene; Messerini, Luca; Guiducci, Serena; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

2014-01-01

Systemic sclerosis (SSc) is a complex connective tissue disease characterized by fibrosis of the skin and various internal organs. In SSc, telocytes, a peculiar type of stromal (interstitial) cells, display severe ultrastructural damages and are progressively lost from the clinically affected skin. The aim of the present work was to investigate the presence and distribution of telocytes in the internal organs of SSc patients. Archival paraffin-embedded samples of gastric wall, myocardium and lung from SSc patients and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were studied on tissue sections subjected to CD34 immunostaining. CD34/CD31 double immunofluorescence was performed to unequivocally differentiate telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). Few telocytes entrapped in the fibrotic extracellular matrix were found in the muscularis mucosae and submucosa of SSc gastric wall. In the muscle layers and myenteric plexus, the network of telocytes was discontinuous or even completely absent around smooth muscle cells and ganglia. Telocytes were almost completely absent in fibrotic areas of SSc myocardium. In SSc fibrotic lung, few or no telocytes were observed in the thickened alveolar septa, around blood vessels and in the interstitial space surrounding terminal and respiratory bronchioles. In SSc, the loss of telocytes is not restricted to the skin, but it is a widespread process affecting multiple organs targeted by the fibrotic process. As telocytes are believed to be key players in the regulation of tissue/organ homoeostasis, our data suggest that telocyte loss might have important pathophysiological implications in SSc. PMID:24467430

Heart Valve Biomechanics and Underlying Mechanobiology

PubMed Central

Ayoub, Salma; Ferrari, Giovanni; Gorman, Robert C.; Gorman, Joseph H.; Schoen, Frederick J.; Sacks, Michael S.

2017-01-01

Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling. We begin with an overview of the fundamentals of heart valve physiology and the characteristics and functions of valve interstitial cells (VICs). We then provide an overview of current experimental and computational approaches that connect VIC mechanobiological response to organ- and tissue-level deformations and improve our understanding of the underlying functional physiology of heart valves. We conclude with a summary of future trends and offer an outlook for the future of heart valve mechanobiology, specifically, multiscale modeling approaches, and the potential directions and possible challenges of research development. PMID:27783858

Transbronchial cryobiopsy in interstitial lung disease: experience in 106 cases – how to do it

PubMed Central

Bango-Álvarez, Antonio; Torres-Rivas, Hector; Fernández-Fernández, Luis; Prieto, Amador; Sánchez, Inmaculada; Gil, Maria; Pando-Sandoval, Ana

2017-01-01

Transbronchial biopsy using forceps (TBB) is the first diagnostic technique performed on patients with interstitial lung disease (ILD). However, the small size of the samples and the presence of artefacts in the tissue obtained make the yield variable. Our objectives were 1) to attempt to reproduce transbronchial cryobiopsy under the same conditions with which we performed conventional TBB, that is, in the bronchoscopy unit without intubating the patient and without fluoroscopy or general anaesthesia; 2) to describe the method used for its execution; and 3) to analyse the diagnostic yield and its complications. We carried out a prospective study that included 106 patients with clinical and radiological features suggestive of ILD who underwent cryo-transbronchial lung biopsy (cryo-TBB) under moderate sedation without endotracheal intubation, general anaesthesia or use of fluoroscopy. We performed the procedure using two flexible bronchoscopes connected to two video processors, which we alternated until obtaining the number of desired samples. A definitive diagnosis was obtained in 91 patients (86%). As for complications, there were five pneumothoraces (4.7%) and in no case was there severe haemorrhage or exacerbation of the underlying interstitial disease. Cryo-TBB following our method is a minimally invasive, rapid, safe and economic technique that can be performed in a bronchoscopy suite under moderate sedation without the need for intubating the patient or using fluoroscopy and without requiring general anaesthesia. PMID:28344982

Separation of Solid Stress From Interstitial Fluid Pressure in Pancreas Cancer Correlates With Collagen Area Fraction.

PubMed

Nieskoski, Michael D; Marra, Kayla; Gunn, Jason R; Kanick, Stephen C; Doyley, Marvin M; Hasan, Tayyaba; Pereira, Stephen P; Stuart Trembly, B; Pogue, Brian W

2017-06-01

Elevated total tissue pressure (TTP) in pancreatic adenocarcinoma is often associated with stress applied by cellular proliferation and hydrated hyaluronic acid osmotic swelling; however, the causal roles of collagen in total tissue pressure have yet to be clearly measured. This study illustrates one direct correlation between total tissue pressure and increased deposition of collagen within the tissue matrix. This observation comes from a new modification to a conventional piezoelectric pressure catheter, used to independently separate and quantify total tissue pressure, solid stress (SS), and interstitial fluid pressure (IFP) within the same tumor location, thereby clarifying the relationship between these parameters. Additionally, total tissue pressure shows a direct correlation with verteporfin uptake, demonstrating the impediment of systemically delivered molecules with increased tissue hypertension.

Role of lipids in the progression of renal disease in systemic lupus erythematosus patients.

PubMed

Luzar, B; Ferluga, D

2000-08-25

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstitial lesions in two patients with lupus nephritis associated with pronounced hyper- and dyslipidemia. The pathogenesis of progressive glomerulosclerosis in both patients appears to be multifactorial. In addition to immune complex mediated lupus glomerulonephritis, progressively active in the first patient, severe nephrotic-range persistent proteinuria, arterial hypertension associated with hyperfiltration and hyperperfusion injuries and, to a minor extent, hyper- and dyslipidemia were observed. Immunological and non-immunological factors were shown to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstitial lipid deposits were probably causally related to both hyperlipidemia and the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as small cleft-like spaces found to be impacted in the tubular lumina. They were seen to penetrate tubular epithelial cells and eventually lodge in the interstitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune deposits were demonstrated. In addition, in the second patient, arteriolar and small arterial hyaline was found at the age of 28 years to be full of lipids and calcium precipitates, suggesting a peripheral atherosclerosis-like process which never occurs as a natural age-related condition. In conclusion, all parts of the nephron may be involved in the pathogenetic process causally related or influenced by hyper- or dyslipidemia. Associated either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltration, or tubulo-interstitial lipid deposition, the mechanism of tissue damage by lipids in all parts of the nephron shares similarities with the pathogenesis of systemic atherosclerosis.

Cytokine signalling in rat pulp interstitial fluid and transcapillary fluid exchange during lipopolysaccharide-induced acute inflammation

PubMed Central

Bletsa, Athanasia; Berggreen, Ellen; Fristad, Inge; Tenstad, Olav; Wiig, Helge

2006-01-01

The dental pulp consists of loose connective tissue encased in rigid dentinal walls. Because of its topography the tissue has low interstitial compliance and limited capacity to expand during fluid volume changes. Due to limitations regarding access to interstitial fluid, basic knowledge on transcapillary fluid transport parameters is lacking for this organ. The scope of this project was dual: first we aimed at establishing a method for isolation of pulp interstitial fluid (IF), and second we applied the method in rats subjected to lipopolysaccharide (LPS)-induced endotoxaemia. The aim was to measure colloid osmotic pressure (COP) and pro-inflammatory cytokines in the pulp IF during acute inflammation. Fluid volumes and pulpal blood flow (PBF) were measured to obtain more information about microcirculatory changes that take place in this pulpitis model. By centrifugation of incisor pulp at 239 g we were able to extract fluid representative for IF. Pulp IF had a relative high control COP (∼83% of plasma COP) and was similar to plasma COP 3 h after LPS challenge. The pulp exhibited a high content of IF (0.60 ± 0.03 ml (g wet weight)−1) and a vascular volume of 0.03 ± 0.01 ml (g w.w.)−1 No differences were observed in the distribution of fluid volumes after 1.5 and 3 h LPS exposure. PBF and systemic blood pressure dropped significantly after LPS administration. PBF remained low whereas systemic blood pressure was re-established during the 3-h period, implying organ dysfunction. There was a differential pattern of cytokine expression in pulp IF and serum with cytokines such as IL-1α, IL-1β and TNF-α locally produced, whereas others such as IFN-γ and IL-6 were produced systemically and probably spilled over to the pulp IF after LPS exposure. Our findings show that pulp IF can be isolated by centrifugation and that this method is useful when studying fluid balance and extracellular signalling mechanisms in the dental pulp in normal and pathological conditions. PMID:16527857

CERA Attenuates Kidney Fibrogenesis in the db/db Mouse by Influencing the Renal Myofibroblast Generation

PubMed Central

Fischer, Christin; Deininger, Natalie; Wolf, Gunter; Loeffler, Ivonne

2018-01-01

Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing myofibroblasts can originate from different sources and different mechanisms are involved in the activation process of the myofibroblasts in the fibrotic kidney. In this study, 16-week-old db/db mice, a model for type 2 DN, were treated for two weeks with continuous erythropoietin receptor activator (CERA), a synthetic erythropoietin variant with possible non-hematopoietic, tissue-protective effects. Non-diabetic and diabetic mice treated with placebo were used as controls. The effects of CERA on tubulointerstitial fibrosis (TIF) as well as on the generation of the matrix-producing myofibroblasts were evaluated by morphological, immunohistochemical, and molecular biological methods. The placebo-treated diabetic mice showed significant signs of beginning renal TIF (shown by picrosirius red staining; increased connective tissue growth factor (CTGF), fibronectin and collagen I deposition; upregulated KIM1 expression) together with an increased number of interstitial myofibroblasts (shown by different mesenchymal markers), while kidneys from diabetic mice treated with CERA revealed less TIF and fewer myofibroblasts. The mechanisms, in which CERA acts as an anti-fibrotic agent/drug, seem to be multifaceted: first, CERA inhibits the generation of matrix-producing myofibroblasts and second, CERA increases the ability for tissue repair. Many of these CERA effects can be explained by the finding that CERA inhibits the renal expression of the cytokine TGF-β1. PMID:29385703

CERA Attenuates Kidney Fibrogenesis in the db/db Mouse by Influencing the Renal Myofibroblast Generation.

PubMed

Fischer, Christin; Deininger, Natalie; Wolf, Gunter; Loeffler, Ivonne

2018-01-30

Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing myofibroblasts can originate from different sources and different mechanisms are involved in the activation process of the myofibroblasts in the fibrotic kidney. In this study, 16-week-old db / db mice, a model for type 2 DN, were treated for two weeks with continuous erythropoietin receptor activator (CERA), a synthetic erythropoietin variant with possible non-hematopoietic, tissue-protective effects. Non-diabetic and diabetic mice treated with placebo were used as controls. The effects of CERA on tubulointerstitial fibrosis (TIF) as well as on the generation of the matrix-producing myofibroblasts were evaluated by morphological, immunohistochemical, and molecular biological methods. The placebo-treated diabetic mice showed significant signs of beginning renal TIF (shown by picrosirius red staining; increased connective tissue growth factor (CTGF), fibronectin and collagen I deposition; upregulated KIM1 expression) together with an increased number of interstitial myofibroblasts (shown by different mesenchymal markers), while kidneys from diabetic mice treated with CERA revealed less TIF and fewer myofibroblasts. The mechanisms, in which CERA acts as an anti-fibrotic agent/drug, seem to be multifaceted: first, CERA inhibits the generation of matrix-producing myofibroblasts and second, CERA increases the ability for tissue repair. Many of these CERA effects can be explained by the finding that CERA inhibits the renal expression of the cytokine TGF-β1.

Exploiting unsupervised and supervised classification for segmentation of the pathological lung in CT

NASA Astrophysics Data System (ADS)

Korfiatis, P.; Kalogeropoulou, C.; Daoussis, D.; Petsas, T.; Adonopoulos, A.; Costaridou, L.

2009-07-01

Delineation of lung fields in presence of diffuse lung diseases (DLPDs), such as interstitial pneumonias (IP), challenges segmentation algorithms. To deal with IP patterns affecting the lung border an automated image texture classification scheme is proposed. The proposed segmentation scheme is based on supervised texture classification between lung tissue (normal and abnormal) and surrounding tissue (pleura and thoracic wall) in the lung border region. This region is coarsely defined around an initial estimate of lung border, provided by means of Markov Radom Field modeling and morphological operations. Subsequently, a support vector machine classifier was trained to distinguish between the above two classes of tissue, using textural feature of gray scale and wavelet domains. 17 patients diagnosed with IP, secondary to connective tissue diseases were examined. Segmentation performance in terms of overlap was 0.924±0.021, and for shape differentiation mean, rms and maximum distance were 1.663±0.816, 2.334±1.574 and 8.0515±6.549 mm, respectively. An accurate, automated scheme is proposed for segmenting abnormal lung fields in HRC affected by IP

Interstitial ablation and imaging of soft tissue using miniaturized ultrasound arrays

NASA Astrophysics Data System (ADS)

Makin, Inder R. S.; Gallagher, Laura A.; Mast, T. Douglas; Runk, Megan M.; Faidi, Waseem; Barthe, Peter G.; Slayton, Michael H.

2004-05-01

A potential alternative to extracorporeal, noninvasive HIFU therapy is minimally invasive, interstitial ultrasound ablation that can be performed laparoscopically or percutaneously. Research in this area at Guided Therapy Systems and Ethicon Endo-Surgery has included development of miniaturized (~3 mm diameter) linear ultrasound arrays capable of high power for bulk tissue ablation as well as broad bandwidth for imaging. An integrated control system allows therapy planning and automated treatment guided by real-time interstitial B-scan imaging. Image quality, challenging because of limited probe dimensions and channel count, is aided by signal processing techniques that improve image definition and contrast. Simulations of ultrasonic heat deposition, bio-heat transfer, and tissue modification provide understanding and guidance for development of treatment strategies. Results from in vitro and in vivo ablation experiments, together with corresponding simulations, will be described. Using methods of rotational scanning, this approach is shown to be capable of clinically relevant ablation rates and volumes.

Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

PubMed Central

Mason, Roger M

2013-01-01

Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

Three-dimensional histology: tools and application to quantitative assessment of cell-type distribution in rabbit heart

PubMed Central

Burton, Rebecca A.B.; Lee, Peter; Casero, Ramón; Garny, Alan; Siedlecka, Urszula; Schneider, Jürgen E.; Kohl, Peter; Grau, Vicente

2014-01-01

Aims Cardiac histo-anatomical organization is a major determinant of function. Changes in tissue structure are a relevant factor in normal and disease development, and form targets of therapeutic interventions. The purpose of this study was to test tools aimed to allow quantitative assessment of cell-type distribution from large histology and magnetic resonance imaging- (MRI) based datasets. Methods and results Rabbit heart fixation during cardioplegic arrest and MRI were followed by serial sectioning of the whole heart and light-microscopic imaging of trichrome-stained tissue. Segmentation techniques developed specifically for this project were applied to segment myocardial tissue in the MRI and histology datasets. In addition, histology slices were segmented into myocytes, connective tissue, and undefined. A bounding surface, containing the whole heart, was established for both MRI and histology. Volumes contained in the bounding surface (called ‘anatomical volume’), as well as that identified as containing any of the above tissue categories (called ‘morphological volume’), were calculated. The anatomical volume was 7.8 cm3 in MRI, and this reduced to 4.9 cm3 after histological processing, representing an ‘anatomical’ shrinkage by 37.2%. The morphological volume decreased by 48% between MRI and histology, highlighting the presence of additional tissue-level shrinkage (e.g. an increase in interstitial cleft space). The ratio of pixels classified as containing myocytes to pixels identified as non-myocytes was roughly 6:1 (61.6 vs. 9.8%; the remaining fraction of 28.6% was ‘undefined’). Conclusion Qualitative and quantitative differentiation between myocytes and connective tissue, using state-of-the-art high-resolution serial histology techniques, allows identification of cell-type distribution in whole-heart datasets. Comparison with MRI illustrates a pronounced reduction in anatomical and morphological volumes during histology processing. PMID:25362175

Interstitial pneumonia with autoimmune features: an additional risk factor for ARDS?

PubMed

Grasselli, Giacomo; Vergnano, Beatrice; Pozzi, Maria Rosa; Sala, Vittoria; D'Andrea, Gabriele; Scaravilli, Vittorio; Mantero, Marco; Pesci, Alberto; Pesenti, Antonio

2017-09-18

Interstitial pneumonia with autoimmune features (IPAF) identifies a recently recognized autoimmune syndrome characterized by interstitial lung disease and autoantibodies positivity, but absence of a specific connective tissue disease diagnosis or alternative etiology. We retrospectively reviewed the clinical presentation, diagnostic workup and management of seven critically ill patients who met diagnostic criteria for IPAF. We compared baseline characteristics and clinical outcome of IPAF patients with those of the population of ARDS patients admitted in the same period. Seven consecutive patients with IPAF admitted to intensive care unit for acute respiratory distress syndrome (ARDS) were compared with 78 patients with ARDS secondary to a known risk factor and with eight ARDS patients without recognized risk factors. Five IPAF patients (71%) survived and were discharged alive from ICU: Their survival rate was equal to that of patients with a known risk factor (71%), while the subgroup of patients without risk factors had a markedly lower survival (38%). According to the Berlin definition criteria, ARDS was severe in four IPAF patients and moderate in the remaining three. All had multiple organ dysfunction at presentation. The most frequent autoantibody detected was anti-SSA/Ro52. All patients required prolonged mechanical ventilation (median duration 49 days, range 10-88); four received extracorporeal membrane oxygenation and one received low-flow extracorporeal CO 2 removal. All patients received immunosuppressive therapy. This is the first description of a cohort of critical patients meeting the diagnostic criteria for IPAF presenting with ARDS. This diagnosis should be considered in any critically ill patient with interstitial lung disease of unknown origin. While management is challenging and level of support high, survival appears to be good and comparable to that of patients with ARDS associated with a known clinical insult.

Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy.

PubMed

Chen, Na; Chen, Meimei; Liu, Shupeng; Guo, Qiang; Chen, Zhenyi; Wang, Tingyun

2014-01-01

This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT.

[Features of the structure and parameters of the intra-alveolar septa in residents of Western Siberia].

PubMed

Shishkin, G S; Ustiuzhaninova, N V

1998-01-01

In inhabitants of Novosibirsk and Moscow district intraalveolar septum, the basic functional element of the lung consists of interstitial connective tissue and capillar network, limited with basement membranes, on which cells of epithelial lining are placed. There are no principal differences in septal structure between individuals from both regions. The majority of morphometric parameters are statistically similar, although certain peculiarities were noted in human subjects from Siberia, the most important of which is that air-blood barrier in them is 33% thinner than those in inhabitants of Moscow district. Majority of capillaries possess the air-blood barrier from both sides. This increases diffous capacity of the lungs and blood oxygenation level.

[Antisynthetase syndrome - a case report].

PubMed

Prus, Visnja; Bedeković, Drazen; Milas-Ahić, Jasminka; Visević, Roberta; Segec, Branko; Jukić, Zlatica; Perić, Ljiljana

2013-01-01

Twenty-eight year-old woman with predominant signs of polymyositis, pulmonary interstitium involvement and with positive anti-Jo1 antibodies was suspected for antisynthetase syndrome. Over the next three months sores and ulcerations have appeared at the fingertips. In the later course of the disease clinical picture of mixed connective tissue disease associated with interstitial lung disease, with a dominant picture of systemic sclerosis have emerged. She was treated with glucocorticoides and immunosuppressive therapy. Patient condition was mostly stable, without significant progression of lung lesions. Early diagnosis and treatment antisynthetase syndrome significantly contributes to more favorable course and outcome of disease. A prerequisite for that are well-defined diagnostic criteria and an appropriate choice of treatment.

Blood glucose level reconstruction as a function of transcapillary glucose transport.

PubMed

Koutny, Tomas

2014-10-01

A diabetic patient occasionally undergoes a detailed monitoring of their glucose levels. Over the course of a few days, a monitoring system provides a detailed track of their interstitial fluid glucose levels measured in their subcutaneous tissue. A discrepancy in the blood and interstitial fluid glucose levels is unimportant because the blood glucose levels are not measured continuously. Approximately five blood glucose level samples are taken per day, and the interstitial fluid glucose level is usually measured every 5min. An increased frequency of blood glucose level sampling would cause discomfort for the patient; thus, there is a need for methods to estimate blood glucose levels from the glucose levels measured in subcutaneous tissue. The Steil-Rebrin model is widely used to describe the relationship between blood and interstitial fluid glucose dynamics. However, we measured glucose level patterns for which the Steil-Rebrin model does not hold. Therefore, we based our research on a different model that relates present blood and interstitial fluid glucose levels to future interstitial fluid glucose levels. Using this model, we derived an improved model for calculating blood glucose levels. In the experiments conducted, this model outperformed the Steil-Rebrin model while introducing no additional requirements for glucose sample collection. In subcutaneous tissue, 26.71% of the calculated blood glucose levels had absolute values of relative differences from smoothed measured blood glucose levels less than or equal to 5% using the Steil-Rebrin model. However, the same difference interval was encountered in 63.01% of the calculated blood glucose levels using the proposed model. In addition, 79.45% of the levels calculated with the Steil-Rebrin model compared with 95.21% of the levels calculated with the proposed model had 20% difference intervals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modeling viscous dissipation during vocal fold contact: the influence of tissue viscosity and thickness with implications for hydration.

PubMed

Erath, Byron D; Zañartu, Matías; Peterson, Sean D

2017-06-01

The mechanics of vocal fold contact during phonation is known to play a crucial role in both normal and pathological speech production, though the underlying physics is not well understood. Herein, a viscoelastic model of the stresses during vocal fold contact is developed. This model assumes the cover to be a poroelastic structure wherein interstitial fluid translocates in response to mechanical squeezing. The maximum interstitial fluid pressure is found to generally increase with decreasing viscous dissipation and/or decreasing tissue elasticity. A global minimum in the total contact stress, comprising interstitial fluid pressure and elastic stress in the tissue, is observed over the studied dimensionless parameter range. Interestingly, physiologically reasonable estimates for the governing parameters fall within this global minimum region. The model is validated against prior experimental and computational work, wherein the predicted contact stress magnitude and impact duration agree well with published results. Lastly, observations of the potential relationship between vocal fold hydration and increased risk of tissue damage are discussed based upon model predictions of stress as functions of cover layer thickness and viscosity.

Bioavailability of insulin detemir and human insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion.

PubMed

Bodenlenz, M; Ellmerer, M; Schaupp, L; Jacobsen, L V; Plank, J; Brunner, G A; Wutte, A; Aigner, B; Mautner, S I; Pieber, T R

2015-12-01

To find an explanation for the lower potency of insulin detemir observed in humans compared with unmodified human insulin by investigating insulin detemir and human insulin concentrations directly at the level of peripheral insulin-sensitive tissues in humans in vivo. Euglycaemic-hyperinsulinaemic clamp experiments were performed in healthy volunteers. Human insulin was administered i.v. at 6 pmol/kg/min and insulin detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, insulin detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human insulin and insulin detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. The human insulin concentration in the ISF was ∼115 pmol/l or ∼30% of the serum concentration, whereas the insulin detemir concentration in the ISF was ∼680 pmol/l or ∼2% of the serum concentration. The molar insulin detemir interstitial concentration was five to six times higher than the human insulin interstitial concentration and metabolic clearance of insulin detemir from serum was substantially reduced compared with human insulin. OFM proved useful for target tissue measurements of human insulin and the analogue insulin detemir. Our tissue data confirm a highly effective retention of insulin detemir in the vascular compartment. The higher insulin detemir relative to human insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of insulin detemir in humans is attributable to a reduced effect in peripheral insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity. © 2015 John Wiley & Sons Ltd.

The deep muscular plexus of the pig duodenum: a histochemical and ultrastructural study with special reference to the interstitial cells.

PubMed

Henry, M; Porcher, C; Julé, Y

1998-06-10

The aim of the present study was to describe the deep muscular plexus of the pig duodenum and to characterize its cellular components. Numerous nerve varicosities have been detected in the deep muscular plexus using anti-synaptophysin antibodies. Nerve fibres were also detected here in the outer circular muscle layer, whereas no nerve fibres were observed in the inner circular muscle layer. In the deep muscular plexus, nerve fibres projected to interstitial cells which were characterized at the ultrastructural level. The interstitial cells were of two kinds: the interstitial fibroblastic-like cells (FLC) and the interstitial dense cells (IDC), both of which were interposed between nerve fibres and smooth muscle cells. The FLC were characterized by their elongated bipolar shape, the lack of basal lamina, a well-developed endoplasmic reticulum, a Golgi apparatus, and intermediate filaments. They were closely apposed to axon terminals containing small clear synaptic vesicles and/or dense-cored vesicles. They were frequently connected to each other and to smooth muscle cells of the inner and outer circular layer by desmosomes and more rarely by gap junctions. The IDC are myoid-like cells. They had a stellate appearance and were characterized by a dense cell body, numerous caveolae, and a discontinuous basal lamina. The IDC were always closely apposed to nerve fibres and were connected to smooth muscle cells by desmosomes and small gap junctions. The present results show the unique pattern of cellular organization of the deep muscular plexus of the pig small intestine. They suggest that the interstitial cells in the deep muscular plexus are involved in the integration and transmission of nervous inputs from myenteric neurons to the inner and outer circular muscle layers. The clear-cut distinction observed here between the two types of interstitial cells (fibroblastic and myoid-like) suggests that the interstitial cells of each type may also be involved in some other specific activity, which still remains to be determined.

High levels of the extracellular matrix proteoglycan decorin are associated with inhibition of testicular function

PubMed Central

Adam, Marion; Urbanski, Henryk F.; Garyfallou, Vasilios T.; Welsch, Ulrich; Köhn, Frank M.; Schwarzer, J. Ullrich; Strauss, Leena; Poutanen, Matti; Mayerhofer, Artur

2011-01-01

Decorin (DCN), a component of the extracellular matrix of the peritubular wall and the interstitial areas of the human testis, can interact with growth factor (GF) signaling, thereby blocking downstream actions of GFs. In the present study the expression and regulation of DCN using both human testes and two experimental animal models, namely the rhesus monkey and mouse, were examined. DCN protein was present in peritubular and interstitial areas of adult human and monkey testes, while it was almost undetectable in adult wild-type mice. Interestingly, the levels and sites of testicular DCN expression in the monkeys were inversely correlated with testicular maturation markers. A strong DCN expression associated with the abundant connective tissue of the interstitial areas in the postnatal through prepubertal phases was observed. In adult and old monkeys the DCN pattern was similar to the one in normal human testes, presenting strong expression at the peritubular region. In the testes of both infertile men and in a mouse model of inflammation associated infertility (aromatase-overexpressing transgenic mice), the fibrotic changes and increased numbers of Tumor necrosis factor (TNF)-α-producing immune cells were shown to be associated with increased production of DCN. Furthermore, studies with human testicular peritubular cells isolated from fibrotic testis indicated that TNF-α significantly increased DCN production. The data, thus, show that an increased DCN level is associated with impaired testicular function, supporting our hypothesis that DCN interferes with paracrine signaling of the testis in health and disease. PMID:22413766

Asbestosis

MedlinePlus

Pulmonary fibrosis - from asbestos exposure; Interstitial pneumonitis - from asbestos exposure ... Breathing in asbestos fibers can cause scar tissue (fibrosis) to form inside the lung. Scarred lung tissue does not expand and ...

Interstitial granulomatous dermatitis with arthritis.

PubMed

Long, D; Thiboutot, D M; Majeski, J T; Vasily, D B; Helm, K F

1996-06-01

Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis. We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis. Skin biopsy specimens were examined and correlated with the clinical and laboratory findings. Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent. Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.

Pulmonary manifestations in systemic lupus erythematosus: pleural involvement, acute pneumonitis, chronic interstitial lung disease and diffuse alveolar hemorrhage.

PubMed

Aguilera-Pickens, Georgina; Abud-Mendoza, Carlos

2018-05-14

Systemic lupus erythematosus is the diffuse autoimmune connective tissue disease that most frequently involves pulmonary involvement, affecting 20% of 90% of the patients. The percentage varies depending on the defining criteria (symptoms, pulmonary tests or histopathological studies). At least once during the disease course, 50% of those affected have pleural and/or pulmonary manifestations, which are associated with higher morbidity and mortality. Pulmonary involvement has no correlation with lupus activity biomarkers, and it is necessary to rule out infectious processes in the initial approach. Bacterial infection is most frequently the cause of lung involvement in lupus and is one of the most important causes of death. Pulmonary involvement is considered to be primary when it is associated with disease activity, and secondary when other causes participate. Drugs have been reported to be associated with pulmonary damage, including interstitial disease. The incidence of malignant lung diseases is increased in systemic lupus erythematosus. Treatment depends on the type and severity of pulmonary involvement. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

A birdcage model for the Chinese meridian system: part III. Possible mechanism of magnetic therapy.

PubMed

Yung, Kaung-Ti

2005-01-01

Based on the electromagnetic model of the transmission line for the channel and the birdcage resonator for the meridian network, we interpret two effects, seemingly incomprehensible in terms of current Western physiology, the lasting effect and the remote effect. For the lasting effect, acupuncture enhances the amplitude of the Qi standing wave, and this increased amplitude is retained and thus is able to sustain a gradual remodeling of the extracellular matrix in interstitial connective tissues, resulting in a lasting therapeutic effect. For the remote effect (acupuncture effect far from the site of needle insertion), our model puts the mechanism of magnetic therapy on an equal footing with that of acupuncture. It may not be a coincidence that accounts of investigators in both acupuncture and magnetotherapy about the depth of the effective site--along cleavage planes between muscles, or between muscle and bone or tendon--are in accord with that of the Huang Di Nei Jing about the course of channels: "they are embedded and travel between interstitial muscles, deep and invisible." A possible magnetic field generated outside the birdcage may be manipulated to produce local areas of higher temperature or very strong fields.

Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review.

PubMed

Atzeni, Fabiola; Gerardi, Maria Chiara; Barilaro, Giuseppe; Masala, Ignazio Francesco; Benucci, Maurizio; Sarzi-Puttini, Piercarlo

2018-01-01

Interstitial lung diseases (ILDs) are among the most serious complications associated with systemic rheumatic diseases, and lead to significant morbidity and mortality; they may also be the first manifestation of connective tissue diseases (CTDs). The aim of this narrative review is to summarise the data concerning the pathogenesis of CTD/ILD and its distinguishing features in different rheumatic diseseas. Areas covered: The pathogenesis, clinical aspects and treatment of ILD associated with rheumatic systemic diseases and CTDs were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1995 and February 2017 using combinations of words or terms. Articles not written in English were excluded. Expert commentary: The management of CTD-ILD is challenging because of the lack of robust data regarding the treatments used, the heterogeneity of the diseases themselves, and the scarcity of well-defined outcome measures. Treatment decisions are often made clinically on the basis of functional, radiographic progression, and exacerbating factors such as age and the burden of comorbidities. Given the complexities of diagnosis and the paucity of treatment trials, the management of CTD patients with ILD requires multidisciplinary collaboration between rheumatologists and pulmonologists in CTD-ILD clinics.

Interstitial protein alterations in rabbit vocal fold with scar.

PubMed

Thibeault, Susan L; Bless, Diane M; Gray, Steven D

2003-09-01

Fibrous and interstitial proteins compose the extracellular matrix of the vocal fold lamina propria and account for its biomechanic properties. Vocal fold scarring is characterized by altered biomechanical properties, which create dysphonia. Although alterations of the fibrous proteins have been confirmed in the rabbit vocal fold scar, interstitial proteins, which are known to be important in wound repair, have not been investigated to date. Using a rabbit model, interstitial proteins decorin, fibromodulin, and fibronectin were examined immunohistologically, two months postinduction of vocal fold scar by means of forcep biopsy. Significantly decreased decorin and fibromodulin with significantly increased fibronectin characterized scarred vocal fold tissue. The implications of altered interstitial proteins levels and their affect on the fibrous proteins will be discussed in relation to increased vocal fold stiffness and viscosity, which characterizes vocal fold scar.

Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model

NASA Astrophysics Data System (ADS)

Swartling, Johannes; Höglund, Odd V.; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie

2016-02-01

Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.

Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.

PubMed

Hayden, Melvin R; Patel, Kamlesh; Habibi, Javad; Gupta, Deepa; Tekwani, Seema S; Whaley-Connell, Adam; Sowers, James R

2008-01-01

Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.

Attenuation of Endocrine-Exocrine Pancreatic Communication in Type 2 Diabetes: Pancreatic Extracellular Matrix Ultrastructural Abnormalities

PubMed Central

Hayden, Melvin R; Patel, Kamlesh; Habibi, Javad; Gupta, Deepa; Tekwani, Seema S.; Whaley-Connell, Adam; Sowers, James R.

2009-01-01

Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet exocrine interface (IEI) appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts – pancreatic stellate cells. Importantly, some pericyte cellular processes traverse both the connecting IEI and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal – incretin gut hormone axis resulting in pancreatic insufficiency and glucagon like peptide deficiency known to exist in prediabetes and overt T2DM in humans. PMID:19040593

Habitat heterogeneity and connectivity shape microbial communities in South American peatlands.

PubMed

Oloo, Felix; Valverde, Angel; Quiroga, María Victoria; Vikram, Surendra; Cowan, Don; Mataloni, Gabriela

2016-05-10

Bacteria play critical roles in peatland ecosystems. However, very little is known of how habitat heterogeneity affects the structure of the bacterial communities in these ecosystems. Here, we used amplicon sequencing of the 16S rRNA and nifH genes to investigate phylogenetic diversity and bacterial community composition in three different sub-Antarctic peat bog aquatic habitats: Sphagnum magellanicum interstitial water, and water from vegetated and non-vegetated pools. Total and putative nitrogen-fixing bacterial communities from Sphagnum interstitial water differed significantly from vegetated and non-vegetated pool communities (which were colonized by the same bacterial populations), probably as a result of differences in water chemistry and biotic interactions. Total bacterial communities from pools contained typically aquatic taxa, and were more dissimilar in composition and less species rich than those from Sphagnum interstitial waters (which were enriched in taxa typically from soils), probably reflecting the reduced connectivity between the former habitats. These results show that bacterial communities in peatland water habitats are highly diverse and structured by multiple concurrent factors.

Development of Targeted Nanobubbles for Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions

DTIC Science & Technology

2015-10-01

interstitial space. Recently, nanodroplets that can extravasate to a tumor’s interstitial space have been developed for targeted imaging 4 and drug...with each pulse applied to a different point in the sample (2 mm spacing) to prevent the effects of cavitation damage from altering the tissue phantom

Pulmonary interstitial fibrosis with evidence of aflatoxin B1 in lung tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dvorackova, I.; Pichova, V.

Three cases of pulmonary interstitial fibrosis, two in agricultural workers and one in a textile worker, are reported. In lung samples of all three patients the presence of aflatoxin B1 was demonstrated by radioimmunoassay (RIA). A possible occupational risk of aflatoxin exposure via the respiratory tract is suggested.

The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

2013-01-01

The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform distribution of oxygen, solid tumor pressure and a broad-based collapse of the tumor lymphatics. We also find that the rate that IFF is fluxed into the lymphatics and host tissue is largely controlled by an elevated vascular hydraulic conductivity in the tumor. We discuss the implications of these results on microenvironmental transport barriers, and the tumor invasive and metastatic potential. Our results suggest the possibility of developing strategies of targeting tumor cells based on the cues in the interstitial fluid. PMID:23220211

Glucose predictability, blood capillary permeability, and glucose utilization rate in subcutaneous, skeletal muscle, and visceral fat tissues.

PubMed

Koutny, Tomas

2013-11-01

This study suggests an approach for the comparison and evaluation of particular compartments with modest experimental setup costs. A glucose level prediction model was used to evaluate the compartment's glucose transport rate across the blood capillary membrane and the glucose utilization rate by the cells. The glucose levels of the blood, subcutaneous tissue, skeletal muscle tissue, and visceral fat were obtained in experiments conducted on hereditary hypertriglyceridemic rats. After the blood glucose level had undergone a rapid change, the experimenter attempted to reach a steady blood glucose level by manually correcting the glucose infusion rate and maintaining a constant insulin infusion rate. The interstitial fluid glucose levels of subcutaneous tissue, skeletal muscle tissue, and visceral fat were evaluated to determine the reaction delay compared with the change in the blood glucose level, the interstitial fluid glucose level predictability, the blood capillary permeability, the effect of the concentration gradient, and the glucose utilization rate. Based on these data, the glucose transport rate across the capillary membrane and the utilization rate in a particular tissue were determined. The rates obtained were successfully verified against positron emission tomography experiments. The subcutaneous tissue exhibits the lowest and the most predictable glucose utilization rate, whereas the skeletal muscle tissue has the greatest glucose utilization rate. In contrast, the visceral fat is the least predictable and has the shortest reaction delay compared with the change in the blood glucose level. The reaction delays obtained for the subcutaneous tissue and skeletal muscle tissue were found to be approximately equal using a metric based on the time required to reach half of the increase in the interstitial fluid glucose level. © 2013 Published by Elsevier Ltd.

Homologous peptide of connective tissue growth factor ameliorates epithelial to mesenchymal transition of tubular epithelial cells.

PubMed

Shi, Yujun; Tu, Zhidan; Wang, Wei; Li, Qing; Ye, Feng; Wang, Jinjing; Qiu, Jing; Zhang, Li; Bu, Hong; Li, Youping

2006-10-01

The hallmark of failing renal transplants is tubular atrophy and interstitial fibrosis. The cytokine connective tissue growth factor (CTGF or CCN2) plays an important role in epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs). A unique domain within CTGF (IRTPKISKPIKFELSG) which binds to its potential receptor integrin alpha v beta3 has been identified. This study was carried out to further characterize a synthetic hexadeca-peptide (P2) homologous to this domain and to determine its effect on CTGF-mediated solid phase cell adhesion, EMT induction and fibrogenesis in rat renal NRK-52E cells. Results showed that both P2 and recombinant CTGF bound to NRK-52E cells. Unlike CTGF, P2 had little effect on EMT induction including cytoskeleton remodeling and expression of alpha-smooth muscle actin (alpha-SMA) and E-cadherin, nor did it have effect on fibrogenic induction including alternation of extracellular matrix (ECM) proteins, collagen type I and IV at gene and protein levels. All data showed that P2 bound preferably on the surface of NRK-52E cells and inhibited the effect of CTGF on EMT induction and cell fibrogenesis, probably by occupying the binding sites of CTGF within its potential receptors. Therefore, P2 may be used as a potential anti-fibrotic agent.

Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus.

PubMed

Saeb-Lima, Marcela; Charli-Joseph, Yann; Rodríguez-Acosta, Elva Dalia; Domínguez-Cherit, Judith

2013-08-01

Neutrophilic dermatoses have long been known to be associated with autoinmune systemic diseases. Recently, a small number of cases of a disorder distinct from Sweet syndrome or bullous lupus erythematosus (LE) have been described as specifically related to systemic LE under diverse terms, including nonbullous neutrophilic dermatosis, nonbullous neutrophilic LE, and Sweet-like neutrophilic dermatosis. We describe 7 patients that developed urticarial lesions in the context of a known or concurrently diagnosed autoimmune connective tissue disease. Of a total of 7 patients, 6 were afflicted by systemic LE and 1 by rheumatoid arthritis and secondary Sjögren syndrome. Histological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, vacuolar alteration along the dermal-edidermal junction, and no vasculitis. Most patients had active systemic disease at the time of the cutaneous eruption. Skin lesions resolved rapidly after the administration of immunomodulating agents. In conclusion, we provide additional evidence of the existence of a recently defined nonbullous neutrophilic dermatosis in the context of autoimmune connective tissue diseases and propose the term autoimmunity-related neutrophilic dermatosis as an appropriate designation. Furthermore, we believe that this entity should prompt physicians to screen the presence of an active systemic disorder in afflicted patients.

AGE-RELATED EFFECT ON THE CONCENTRATION OF COLLAGEN CROSSLINKS IN HUMAN OSTEONAL AND INTERSTITIAL BONE TISSUE

PubMed Central

Nyman, Jeffry S.; Roy, Anuradha; Acuna, Rae L.; Gayle, Heather J.; Reyes, Michael J.; Tyler, Jerrod H.; Dean, David D.; Wang, Xiaodu

2007-01-01

Collagen crosslinks are important to the quality of bone and may be contributors to the age-related increase in bone fracture. This study was performed to investigate whether age and gender effects on collagen crosslinks are similar in osteonal and interstitial bone tissues. Forty human cadaveric femurs were collected and divided into two age groups: Middle aged (42–63 years of age) and Elderly (69–90 years of age) with ten males and ten females in each group (n = 10). Micro-cores of bone tissue from both secondary osteons (newly formed) and interstitial regions (biologically old) in the medial quadrant of the diaphysis were extracted using a custom-modified, computer numerical controlled machine. The bone specimens were then analyzed using high performance liquid chromatography to determine the effects of age and gender on the concentration of mature, enzymatic crosslinks (hydroxylysyl-pyridinoline – HP and lysylpyridinoline – LP) and a non-enzymatic crosslink (pentosidine – PE) at these two bony sites. The results indicate that age has a significant effect on the concentration of LP and PE, while gender has a significant effect on HP and LP. In addition, the concentration of the crosslinks in the secondary osteons is significantly different from that in the interstitial bone regions. These results suggest that the rate of non-enzymatic crosslinking may increase while the formation of maturate enzymatic crosslinks may decrease with age. Such changes could potentially reduce the inherent quality of the bone tissue in the elderly skeleton. PMID:16962838

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

PubMed

Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

2002-04-01

Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.

See-saw nystagmus and brainstem infarction: MRI findings

NASA Technical Reports Server (NTRS)

Kanter, D. S.; Ruff, R. L.; Leigh, R. J.; Modic, M.

1987-01-01

A patient with see-saw nystagmus had a lesion localized by Magnetic Resonance Imaging (MRI) to the paramedian ventral midbrain with involvement of the right interstitial nucleus of Cajal. This the first MRI study of see-saw nystagmus associated with a presumed brainstem vascular event. Our findings support animal and human studies suggesting that dysfunction of the interstitial nucleus of Cajal or its connections is central in this disorder.

The role of the extracellular matrix in tissue distribution of macromolecules in normal and pathological tissues: potential therapeutic consequences.

PubMed

Wiig, Helge; Gyenge, Christina; Iversen, Per Ole; Gullberg, Donald; Tenstad, Olav

2008-05-01

The interstitial space is a dynamic microenvironment that consists of interstitial fluid and structural molecules of the extracellular matrix, such as glycosaminoglycans (hyaluronan and proteoglycans) and collagen. Macromolecules can distribute in the interstitium only in those spaces unoccupied by structural components, a phenomenon called interstitial exclusion. The exclusion phenomenon has direct consequences for plasma volume regulation. Early studies have assigned a major role to collagen as an excluding agent that accounts for the sterical (geometrical) exclusion. More recently, it has been shown that the contribution of negatively charged glycosaminoglycans might also be significant, resulting in an additional electrostatical exclusion effect. This charge effect may be of importance for drug uptake and suggests that either the glycosaminoglycans or the net charge of macromolecular substances to be delivered may be targeted to increase the available volume and uptake of macromolecular therapeutic agents in tumor tissue. Here, we provide an overview of the structural components of the interstitium and discuss the importance the sterical and electrostatical components have on the dynamics of transcapillary fluid exchange.

An analytical model to predict interstitial lubrication of cartilage in migrating contact areas.

PubMed

Moore, A C; Burris, D L

2014-01-03

For nearly a century, articular cartilage has been known for its exceptional tribological properties. For nearly as long, there have been research efforts to elucidate the responsible mechanisms for application toward biomimetic bearing applications. It is now widely accepted that interstitial fluid pressurization is the primary mechanism responsible for the unusual lubrication and load bearing properties of cartilage. Although the biomechanics community has developed elegant mathematical theories describing the coupling of solid and fluid (biphasic) mechanics and its role in interstitial lubrication, quantitative gaps in our understanding of cartilage tribology have inhibited our ability to predict how tribological conditions and material properties impact tissue function. This paper presents an analytical model of the interstitial lubrication of biphasic materials under migrating contact conditions. Although finite element and other numerical models of cartilage mechanics exist, they typically neglect the important role of the collagen network and are limited to a specific set of input conditions, which limits general applicability. The simplified approach taken in this work aims to capture the broader underlying physics as a starting point for further model development. In agreement with existing literature, the model indicates that a large Peclet number, Pe, is necessary for effective interstitial lubrication. It also predicts that the tensile modulus must be large relative to the compressive modulus. This explains why hydrogels and other biphasic materials do not provide significant interstitial pressure under high Pe conditions. The model quantitatively agrees with in-situ measurements of interstitial load support and the results have interesting implications for tissue engineering and osteoarthritis problems. This paper suggests that a low tensile modulus (from chondromalacia or local collagen rupture after impact, for example) may disrupt interstitial pressurization, increase shear stresses, and activate a condition of progressive surface damage as a potential precursor of osteoarthritis. © 2013 Elsevier Ltd. All rights reserved.

Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells

PubMed Central

Cushing, Melinda C.; Mariner, Peter D.; Liao, Jo-Tsu; Sims, Evan A.; Anseth, Kristi S.

2008-01-01

This study aimed to identify signaling pathways that oppose connective tissue fibrosis in the aortic valve. Using valvular interstitial cells (VICs) isolated from porcine aortic valve leaflets, we show that basic fibroblast growth factor (FGF-2) effectively blocks transforming growth factor-β1 (TGF-β1)-mediated myofibroblast activation. FGF-2 prevents the induction of α-smooth muscle actin (αSMA) expression and the exit of VICs from the cell cycle, both of which are hallmarks of myofibroblast activation. By blocking the activity of the Smad transcription factors that serve as the downstream nuclear effectors of TGF-β1, FGF-2 treatment inhibits fibrosis in VICs. Using an exogenous Smad-responsive transcriptional promoter reporter, we show that Smad activity is repressed by FGF-2, likely an effect of the fact that FGF-2 treatment prevents the nuclear localization of Smads in these cells. This appears to be a direct effect of FGF signaling through mitogen-activated protein kinase (MAPK) cascades as the treatment of VICs with the MAPK/extracellular regulated kinase (MEK) inhibitor U0126 acted to induce fibrosis and blocked the ability of FGF-2 to inhibit TGF-β1 signaling. Furthermore, FGF-2 treatment of VICs blocks the development of pathological contractile and calcifying phenotypes, suggesting that these pathways may be utilized in the engineering of effective treatments for valvular disease.—Cushing, M. C., Mariner, P. D., Liao, J. T., Sims, E. A., Anseth, K. S. Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells. PMID:18218921

Laserthermia: a new computer-controlled contact Nd: YAG system for interstitial local hyperthermia.

PubMed

Daikuzono, N; Suzuki, S; Tajiri, H; Tsunekawa, H; Ohyama, M; Joffe, S N

1988-01-01

Contact Nd:YAG laser surgery is assuming a greater importance in endoscopic and open surgery, allowing coagulation, cutting, and vaporization with greater precision and safety. A new contact probe allows a wider angle of irradiation and diffusion of low-power laser energy (less than 5 watts), using the interstitial technique for producing local hyperthermia. Temperature sensors that monitor continuously can be placed directly into the surrounding tissue or tumor. Using a computer program interfaced with the laser and sensors, a controlled and stable temperature (e.g., 42 degrees C) can be produced in a known volume of tissue over a prolonged period of time (e.g., 20-40 min). This new laserthermia system, using a single low-power Nd:YAG laser for interstitial local hyperthermia, may offer many new advantages in the experimental treatment and clinical management of carcinoma. A multiple system is now being developed.

Modeling of heat transfer in a vascular tissue-like medium during an interstitial hyperthermia process.

PubMed

Hassanpour, Saeid; Saboonchi, Ahmad

2016-12-01

This paper aims to evaluate the role of small vessels in heat transfer mechanisms of a tissue-like medium during local intensive heating processes, for example, an interstitial hyperthermia treatment. To this purpose, a cylindrical tissue with two co- and counter-current vascular networks and a central heat source is introduced. Next, the energy equations of tissue, supply fluid (arterial blood), and return fluid (venous blood) are derived using porous media approach. Then, a 2D computer code is developed to predict the temperature of blood (fluid phase) and tissue (solid phase) by conventional volume averaging method and a more realistic solution method. In latter method, despite the volume averaging the blood of interconnect capillaries is separated from the arterial and venous blood phases. It is found that in addition to blood perfusion rate, the arrangement of vascular network has considerable effects on the pattern and amount of the achieved temperature. In contrast to counter-current network, the co-current network of vessels leads to considerable asymmetric pattern of temperature contours and relocation of heat affected zone along the blood flow direction. However this relocation can be prevented by changing the site of hyperthermia heat source. The results show that the cooling effect of co-current blood vessels during of interstitial heating is more efficient. Despite much anatomical dissimilarities, these findings can be useful in designing of protocols for hyperthermia cancer treatment of living tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

PubMed

Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

2016-02-01

Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

Compositional changes in lipid microdomains of air-blood barrier plasma membranes in pulmonary interstitial edema.

PubMed

Palestini, Paola; Calvi, Chiara; Conforti, Elena; Daffara, Rossella; Botto, Laura; Miserocchi, Giuseppe

2003-10-01

We evaluated in anesthetized rabbits the compositional changes of plasmalemmal lipid microdomains from lung tissue samples after inducing pulmonary interstitial edema (0.5 ml/kg for 3 h, leading to approximately 5% increase in extravascular water). Lipid microdomains (lipid rafts and caveolae) were present in the detergent-resistant fraction (DRF) obtained after discontinuous sucrose density gradient. DRF was enriched in caveolin-1, flotillin, aquaporin-1, GM1, cholesterol, sphingomyelin, and phosphatidylserine, and their contents significantly increased in interstitial edema. The higher DRF content in caveolin, flotillin, and aquaporin-1 and of the ganglioside GM1 suggests an increase both in caveolar domains and in lipid rafts, respectively. Compositional changes could be ascribed to endothelial and epithelial cells that provide most of plasma membrane surface area in the air-blood barrier. Alterations in lipid components in the plasma membrane may reflect rearrangement of floating lipid platforms within the membrane and/or lipid translocation from intracellular stores. Lipid traffic could be stimulated by the marked increase in hydraulic interstitial pressure after initial water accumulation, from approximately -10 to 5 cmH2O, due to the low compliance of the pulmonary tissue, in particular in the basement membranes and in the interfibrillar substance. Compositional changes in lipid microdomains represent a sign of cellular activation and suggest the potential role of mechanotransduction in response to developing interstitial edema.

Coal Mine Dust Desquamative Chronic Interstitial Pneumonia: A Precursor of Dust-Related Diffuse Fibrosis and of Emphysema.

PubMed

Jelic, Tomislav M; Estalilla, Oscar C; Sawyer-Kaplan, Phyllis R; Plata, Milton J; Powers, Jeremy T; Emmett, Mary; Kuenstner, John T

2017-07-01

Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. To identify the precursor of dust-related diffuse fibrosis and emphysema. Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Coal miners had 331 birefringent particles/high power field while smokers had 4 (p<0.001). Every coal miner had intra-alveolar macrophages with silica/silicate particles and interstitial fibrosis ranging from minimal to extreme. All coal miners, including those who never smoked, had emphysema. Fibrotic septa of centrilobular emphysema contained numerous silica/silicate particles while only a few were present in adjacent normal lung tissue. In coal miners who smoked, tobacco-associated interstitial fibrosis was replaced by fibrosis caused by silica/silicate particles. The presence of silica/silicate particles and anthracotic pigment-laden macrophages inside the alveoli with various degrees of interstitial fibrosis indicated a new disease: coal mine dust desquamative chronic interstitial pneumonia, a precursor of both dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis caused by smoking is insignificant in comparison with fibrosis caused by silica/silicate particles. Counting birefringent particles in the macrophages from bronchioalveolar lavage may help detect coal mine dust desquamative chronic interstitial pneumonia, and may initiate early therapy and preventive measures.

[Progress in laser neurosurgery].

PubMed

Majchrzak, H; Kopera, M; Idzik, M

1991-01-01

Nd:YAG lasers with different wavelengths are used in neurosurgery. Their great advantage is the ability of coagulation of blood vessels and delivery through flexible fiber optics . Nd:YAG laser with wavelength 1.318 microns is used, besides, to connect blood vessels and nerves. CO2 laser is the best cutting tool but requires, for delivery rigid cable. Both types of lasers cause shrinkage and vaporisation of the tumors what facilitates its removing without greater traumatisation of surrounding tissues. The introduction of sapphire contact tips to Nd:YAG and argon lasers enables application of small laser powers and diminish the area of damage in surrounding structures. Contact laser is used for destroying of tumours, coagulation of blood vessels, restoration of patency of the main arteries, interstitial denaturation of gliomas and denaturation of the nucleus pulposus in lumbar vertebral column.

Development of ex vivo model for determining temperature distribution in tumor tissue during photothermal therapy

NASA Astrophysics Data System (ADS)

Liu, Shaojie; Doughty, Austin; Mesiya, Sana; Pettitt, Alex; Zhou, Feifan; Chen, Wei R.

2017-02-01

Temperature distribution in tissue is a crucial factor in determining the outcome of photothermal therapy in cancer treatment. In order to investigate the temperature distribution in tumor tissue during laser irradiation, we developed a novel ex vivo device to simulate the photothermal therapy on tumors. A 35°C, a thermostatic incubator was used to provide a simulation environment for body temperature of live animals. Different biological tissues (chicken breast and bovine liver) were buried inside a tissue-simulating gel and considered as tumor tissues. An 805-nm laser was used to irradiate the target tissue. A fiber with an interstitial cylindrical diffuser (10 mm) was directly inserted in the center of the tissue, and the needle probes of a thermocouple were inserted into the tissue paralleling the laser fiber at different distances to measure the temperature distribution. All of the procedures were performed in the incubator. Based on the results of this study, the temperature distribution in bovine liver is similar to that of tumor tissue under photothermal therapy with the same doses. Therefore, the developed model using bovine liver for determining temperature distribution can be used during interstitial photothermal therapy.

A mathematical model of intestinal oedema formation.

PubMed

Young, Jennifer; Rivière, Béatrice; Cox, Charles S; Uray, Karen

2014-03-01

Intestinal oedema is a medical condition referring to the build-up of excess fluid in the interstitial spaces of the intestinal wall tissue. Intestinal oedema is known to produce a decrease in intestinal transit caused by a decrease in smooth muscle contractility, which can lead to numerous medical problems for the patient. Interstitial volume regulation has thus far been modelled with ordinary differential equations, or with a partial differential equation system where volume changes depend only on the current pressure and not on updated tissue stress. In this work, we present a computational, partial differential equation model of intestinal oedema formation that overcomes the limitations of past work to present a comprehensive model of the phenomenon. This model includes mass and momentum balance equations which give a time evolution of the interstitial pressure, intestinal volume changes and stress. The model also accounts for the spatially varying mechanical properties of the intestinal tissue and the inhomogeneous distribution of fluid-leaking capillaries that create oedema. The intestinal wall is modelled as a multi-layered, deforming, poroelastic medium, and the system of equations is solved using a discontinuous Galerkin method. To validate the model, simulation results are compared with results from four experimental scenarios. A sensitivity analysis is also provided. The model is able to capture the final submucosal interstitial pressure and total fluid volume change for all four experimental cases, and provide further insight into the distribution of these quantities across the intestinal wall.

The distribution of serum albumin in the rat testis, studied by electron microscope immunocytochemistry on ultrathin frozen sections.

PubMed

Christensen, A K; Komorowski, T E; Wilson, B; Ma, S F; Stevens, R W

1985-05-01

The distribution of serum albumin is of interest in the rat testis because this protein is the principal carrier for testosterone in the plasma and interstitial fluid of this species. We have localized extravascular serum albumin in the rat testis at the electron microscope level, using gold particle immunocytochemistry on ultrathin frozen sections of tissue fixed lightly by perfusion. The same localization was obtained with three different antisera. Preabsorption and normal rabbit serum controls were negative, and Western blots of testis extracts showed major activity only at the molecular weight of albumin. Serum albumin occurred in substantial concentration throughout extracellular space in the interstitial tissue, as well as in the space between the boundary layer and the base of the seminiferous epithelium. Immunoreactivity extended between Sertoli cells, as well as around spermatogonia and early primary spermatocytes (to stage 11), but did not traverse the Sertoli-Sertoli junctions that comprise the blood-testis barrier. Macrophages in the interstitial tissue showed some endocytic activity. If perfusion fixation was carried out in a manner that flushed most of the albumin from the interstitial space, then a layer of albumin remained on the surface of Leydig cells and many macrophages but was minimal or absent on the surface of other cell types that are normally in contact with albumin, such as Sertoli cells, spermatogonia, myoid cells, lymphatic endothelium, fibroblasts, or cells of blood vessels.

Habitat heterogeneity and connectivity shape microbial communities in South American peatlands

PubMed Central

Oloo, Felix; Valverde, Angel; Quiroga, María Victoria; Vikram, Surendra; Cowan, Don; Mataloni, Gabriela

2016-01-01

Bacteria play critical roles in peatland ecosystems. However, very little is known of how habitat heterogeneity affects the structure of the bacterial communities in these ecosystems. Here, we used amplicon sequencing of the 16S rRNA and nifH genes to investigate phylogenetic diversity and bacterial community composition in three different sub-Antarctic peat bog aquatic habitats: Sphagnum magellanicum interstitial water, and water from vegetated and non-vegetated pools. Total and putative nitrogen-fixing bacterial communities from Sphagnum interstitial water differed significantly from vegetated and non-vegetated pool communities (which were colonized by the same bacterial populations), probably as a result of differences in water chemistry and biotic interactions. Total bacterial communities from pools contained typically aquatic taxa, and were more dissimilar in composition and less species rich than those from Sphagnum interstitial waters (which were enriched in taxa typically from soils), probably reflecting the reduced connectivity between the former habitats. These results show that bacterial communities in peatland water habitats are highly diverse and structured by multiple concurrent factors. PMID:27162086

Aggrecan nanoscale solid-fluid interactions are a primary determinant of cartilage dynamic mechanical properties.

PubMed

Nia, Hadi Tavakoli; Han, Lin; Bozchalooi, Iman Soltani; Roughley, Peter; Youcef-Toumi, Kamal; Grodzinsky, Alan J; Ortiz, Christine

2015-03-24

Poroelastic interactions between interstitial fluid and the extracellular matrix of connective tissues are critical to biological and pathophysiological functions involving solute transport, energy dissipation, self-stiffening and lubrication. However, the molecular origins of poroelasticity at the nanoscale are largely unknown. Here, the broad-spectrum dynamic nanomechanical behavior of cartilage aggrecan monolayer is revealed for the first time, including the equilibrium and instantaneous moduli and the peak in the phase angle of the complex modulus. By performing a length scale study and comparing the experimental results to theoretical predictions, we confirm that the mechanism underlying the observed dynamic nanomechanics is due to solid-fluid interactions (poroelasticity) at the molecular scale. Utilizing finite element modeling, the molecular-scale hydraulic permeability of the aggrecan assembly was quantified (kaggrecan = (4.8 ± 2.8) × 10(-15) m(4)/N·s) and found to be similar to the nanoscale hydraulic permeability of intact normal cartilage tissue but much lower than that of early diseased tissue. The mechanisms underlying aggrecan poroelasticity were further investigated by altering electrostatic interactions between the molecule's constituent glycosaminoglycan chains: electrostatic interactions dominated steric interactions in governing molecular behavior. While the hydraulic permeability of aggrecan layers does not change across species and age, aggrecan from adult human cartilage is stiffer than the aggrecan from newborn human tissue.

Induced Autologous Stem Cell Transplantation for Treatment of Rabbit Renal Interstitial Fibrosis

PubMed Central

Ruan, Guang-Ping; Xu, Fan; Li, Zi-An; Zhu, Guang-Xu; Pang, Rong-Qing; Wang, Jin-Xiang; Cai, Xue-Min; He, Jie; Yao, Xiang; Ruan, Guang-Hong; Xu, Xin-Ming; Pan, Xing-Hua

2013-01-01

Introduction Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. Methods A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. Results Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. Conclusions We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function. PMID:24367598

[THE STRUCTURE OF LYMPHATIC CAPILLARIES OF THE CILIARY BODY OF THE HUMAN EYE].

PubMed

Borodin, Yu I; Bgatova, N P; Chernykh, V V; Trunov, A N; Pozhidayeva, A A; Konenkov, V I

2015-01-01

Using light microscopy, immunohistochemistry and electron microscopy, the structural organization of interstitial spaces and vessels of the ciliary body of the human eye (n = 5) were studied. The ciliary body was found to contain wide interstitial spaces--tissue clefts bound by collagen fibers and fibroblasts. Organ-specific lymphatic capillaries were also demonstrated in the ciliary body. According to the present findings and the lymphatic region concept, the first 2 elements of the lymphatic region of the eye were described: tissue clefts--prelymphatics and lymphatic capillaries of the ciliary body. The third element of the lymphatic region are the lymph nodes of the head and neck.

Computer Simulations of the Tumor Vasculature: Applications to Interstitial Fluid Flow, Drug Delivery, and Oxygen Supply.

PubMed

Welter, Michael; Rieger, Heiko

2016-01-01

Tumor vasculature, the blood vessel network supplying a growing tumor with nutrients such as oxygen or glucose, is in many respects different from the hierarchically organized arterio-venous blood vessel network in normal tissues. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature. Integrative models, based on detailed experimental data and physical laws, implement, in silico, the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. This chapter provides an overview over the current status of computer simulations of vascular remodeling during tumor growth including interstitial fluid flow, drug delivery, and oxygen supply within the tumor. The model predictions are compared with experimental and clinical data and a number of longstanding physiological paradigms about tumor vasculature and intratumoral solute transport are critically scrutinized.

Organization and quantification of the elements in the intertubular space in the adult jaguar testis (Panthera onca, LINNAEUS, 1758).

PubMed

Azevedo, Maria Helena Ferreira; Paula, Tarcízio Antônio Rego; Balarini, Maytê Koch; Matta, Sérgio Luiz Pinto; Peixoto, Juliano Vogas; Guião Leite, Flaviana Lima; Rossi, João Luis; da Costa, Eduardo Paulino

2008-12-01

The endocrine portion of mammal testicle is represented by Leydig cells which, together with connective cells, leukocytes, blood and lymphatic vessels, form the intertubular space. The arrangement and proportion of these components vary in the different species of mammals and form mechanisms that keep the testosterone level--the main product of the Leydig cell--two to three times higher in the interstitial fluid than in the testicular blood vessels and 40-250 times higher in these than in the peripheral blood. Marked differences are observed among animal species regarding the abundance of Leydig cells, loose connective tissue, development degree and location of the lymphatic vessels and their topographical relationship with seminiferous tubules. In the jaguar about 13% of the testicular parenchyma is occupied by Leydig cells, 8.3% by connective tissue and 0.3% by lymphatic vessels. Although included in standard II, as described in the literature, concerning the arrangement of the intertubular space, the jaguar has grouped lymphatic vessels in the intertubular space instead of isolated ones. In the jaguar the average volume of the Leydig cell was 2386 microm3 and its average nuclear diameter was 7.7 microm. A great quantity of 2.3 microm diameter lipidic drops was observed in the Leydig cell cytoplasm of the jaguar. The Leydig cells in the jaguar occupy an average 0.0036% of the body weight and the average number per gram of testicle was within the range for most mammals: between 20 and 40 million.

Lung cancer development in patients with connective tissue disease-related interstitial lung disease: A retrospective observational study.

PubMed

Enomoto, Yasunori; Inui, Naoki; Yoshimura, Katsuhiro; Nishimoto, Koji; Mori, Kazutaka; Kono, Masato; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Iwashita, Toshihide; Suda, Takafumi

2016-12-01

Previous studies have reported that patients with idiopathic pulmonary fibrosis occasionally develop lung cancer (LC). However, in connective tissue disease (CTD)-related interstitial lung disease (ILD), there are few data regarding the LC development. The aim of the present study was to evaluate the clinical significance of LC development in patients with CTD-ILD. A retrospective review of our database of 562 patients with ILD between 2000 and 2014 identified 127 patients diagnosed with CTD-ILD. The overall and cumulative incidences of LC were calculated. In addition, the risk factors and prognostic impact of LC development were evaluated. The median age at the ILD diagnosis was 63 years (range 37-84 years), and 73 patients (57.5%) were female. The median follow-up period from the ILD diagnosis was 67.4 months (range 10.4-322.1 months). During the period, 7 out of the 127 patients developed LC (overall incidence 5.5%). The cumulative incidences at 1, 3, and 5 years were 0.0%, 1.8%, and 2.9%, respectively. The risk of LC development was significantly higher in patients with higher smoking pack-year (odds ratio [OR] 1.028; 95% confidence interval [CI] 1.008-1.049; P = 0.007) and emphysema on chest high-resolution computed tomography (OR 14.667; 95% CI 2.871-74.926; P = 0.001). The median overall survival time after developing LC was 7.0 months (95% CI 4.9-9.1 months), and the most common cause of death was LC, not ILD. According to the Cox proportional hazard model analysis with time-dependent covariates, patients who developed LC showed significantly poorer prognosis than those who did not (hazard ratio 87.86; 95% CI 19.56-394.67; P < 0.001). In CTD-ILD, clinicians should be careful with the risk of LC development in patients with a heavy smoking history and subsequent emphysema. Although not so frequent, the complication could be a poor prognostic determinant.

Evaluation of computer-based computer tomography stratification against outcome models in connective tissue disease-related interstitial lung disease: a patient outcome study.

PubMed

Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Brun, Anne Laure; Egashira, Ryoko; Karwoski, Ronald; Kokosi, Maria; Wells, Athol U; Hansell, David M

2016-11-23

To evaluate computer-based computer tomography (CT) analysis (CALIPER) against visual CT scoring and pulmonary function tests (PFTs) when predicting mortality in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). To identify outcome differences between distinct CTD-ILD groups derived following automated stratification of CALIPER variables. A total of 203 consecutive patients with assorted CTD-ILDs had CT parenchymal patterns evaluated by CALIPER and visual CT scoring: honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume, emphysema, and traction bronchiectasis. CT scores were evaluated against pulmonary function tests: forced vital capacity, diffusing capacity for carbon monoxide, carbon monoxide transfer coefficient, and composite physiologic index for mortality analysis. Automated stratification of CALIPER-CT variables was evaluated in place of and alongside forced vital capacity and diffusing capacity for carbon monoxide in the ILD gender, age physiology (ILD-GAP) model using receiver operating characteristic curve analysis. Cox regression analyses identified four independent predictors of mortality: patient age (P < 0.0001), smoking history (P = 0.0003), carbon monoxide transfer coefficient (P = 0.003), and pulmonary vessel volume (P < 0.0001). Automated stratification of CALIPER variables identified three morphologically distinct groups which were stronger predictors of mortality than all CT and functional indices. The Stratified-CT model substituted automated stratified groups for functional indices in the ILD-GAP model and maintained model strength (area under curve (AUC) = 0.74, P < 0.0001), ILD-GAP (AUC = 0.72, P < 0.0001). Combining automated stratified groups with the ILD-GAP model (stratified CT-GAP model) strengthened predictions of 1- and 2-year mortality: ILD-GAP (AUC = 0.87 and 0.86, respectively); stratified CT-GAP (AUC = 0.89 and 0.88, respectively). CALIPER-derived pulmonary vessel volume is an independent predictor of mortality across all CTD-ILD patients. Furthermore, automated stratification of CALIPER CT variables represents a novel method of prognostication at least as robust as PFTs in CTD-ILD patients.

Proliferation and differentiation of brown adipocytes from interstitial cells during cold acclimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bukowiecki, L.J.; Geloeen, A.; Collet, A.J.

1986-06-01

The mechanisms of brown adipocyte proliferation and differentiation during cold acclimation (and/or adaptation to hyperphagia) have been studied by quantitative photonic radioautography. (/sup 3/H)thymidine was injected to warm-acclimated (25/sup 0/C) rats and to animals exposed to 5/sup 0/C for 2 days. Samples of interscapular brown adipose tissue were collected for quantitative analysis of mitotic frequencies at various periods of time (4 h-15 days) after the injection of (/sup 3/H)thymidine, the rats being maintained at the temperatures to which they were initially exposed. It was found that cold exposure for 2 days markedly enhanced mitotic activity in endothelial cells, interstitial cells,more » and brown preadipocytes rather than in fully differentiated brown adipocytes. The total tissue labeling index (percent of labeled nuclei) increased approx.70 times over control values. The authors now report that cellular labeling progressively increased in mature brown adipocytes during cold acclimation, whereas it correspondingly decreased in interstitial cells and brown preadipocytes. This indicates that the sequence of events for cellular differentiation is interstitial cells ..-->.. brown preadipocytes ..-->.. mature brown adipocytes. Remarkable, labeling frequency did not change in endothelial cells during cold acclimation demonstrating that these cells cannot be considered as progenitors of brown adipocytes. It is suggested that brown adipocyte proliferation and differentiation from interstitial cells represent the fundamental phenomena explaining the enhanced capacity of cold-acclimated and/or hyperphagic rats to respond calorigenically to catecholamines.« less

Fibroblasts are in a position to provide directional information to migrating neutrophils during pneumonia in rabbit lungs.

PubMed

Behzad, A R; Chu, F; Walker, D C

1996-05-01

Previous findings have shown that pulmonary fibroblasts are associated with preexisting holes in the endothelial and epithelial basal laminae through which neutrophils appear to enter and leave the interstitium as they migrate from capillaries to alveoli. To determine their role in neutrophil migration, fibroblast organization within the interstitium was assessed by transmission electron microscope observations of serial-sectioned rabbit lung tissue. Interstitial fibroblasts were found to physically interconnect the endothelial basal lamina holes to epithelial basal lamina holes. Morphometric assessment of rabbit lung tissue instilled with Streptococcus pneumoniae revealed that approximately 70% of the surface area density of migrating neutrophils is in close contact (15 nm or less) with interstitial fibroblasts and extracellular matrix elements (30 and 40%, respectively). Although migrating neutrophils were close enough to adhere to both fibroblasts and extracellular elements, the interstitial fibroblasts are organized in a manner that would allow them to provide directional information to the neutrophils. A model illustrating this process is proposed.

Sex steroid receptor expression in idiopathic pulmonary fibrosis.

PubMed

Mehrad, Mitra; Trejo Bittar, Humberto E; Yousem, Samuel A

2017-08-01

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

HRCT findings of collagen vascular disease-related interstitial pneumonia (CVD-IP): a comparative study among individual underlying diseases.

PubMed

Tanaka, N; Kunihiro, Y; Kubo, M; Kawano, R; Oishi, K; Ueda, K; Gondo, T

2018-05-29

To identify characteristic high-resolution computed tomography (CT) findings for individual collagen vascular disease (CVD)-related interstitial pneumonias (IPs). The HRCT findings of 187 patients with CVD, including 55 patients with rheumatoid arthritis (RA), 50 with systemic sclerosis (SSc), 46 with polymyositis/dermatomyositis (PM/DM), 15 with mixed connective tissue disease, 11 with primary Sjögren's syndrome, and 10 with systemic lupus erythematosus, were evaluated. Lung parenchymal abnormalities were compared among CVDs using χ 2 test, Kruskal-Wallis test, and multiple logistic regression analysis. A CT-pathology correlation was performed in 23 patients. In RA-IP, honeycombing was identified as the significant indicator based on multiple logistic regression analyses. Traction bronchiectasis (81.8%) was further identified as the most frequent finding based on χ 2 test. In SSc IP, lymph node enlargement and oesophageal dilatation were identified as the indicators based on multiple logistic regression analyses, and ground-glass opacity (GGO) was the most extensive based on Kruskal-Wallis test, which reflects the higher frequency of the pathological nonspecific interstitial pneumonia (NSIP) pattern present in the CT-pathology correlation. In PM/DM IP, airspace consolidation and the absence of honeycombing were identified as the indicators based on multiple logistic regression analyses, and predominance of consolidation over GGO (32.6%) and predominant subpleural distribution of GGO/consolidation (41.3%) were further identified as the most frequent findings based on χ 2 test, which reflects the higher frequency of the pathological NSIP and/or the organising pneumonia patterns present in the CT-pathology correlation. Several characteristic high-resolution CT findings with utility for estimating underlying CVD were identified. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A computational study of systemic hydration in vocal fold collision.

PubMed

Bhattacharya, Pinaki; Siegmund, Thomas

2014-01-01

Mechanical stresses develop within vocal fold (VF) soft tissues due to phonation-associated vibration and collision. These stresses in turn affect the hydration of VF tissue and thus influence voice health. In this paper, high-fidelity numerical computations are described, taking into account fully 3D geometry, realistic tissue and air properties, and high-amplitude vibration and collision. A segregated solver approach is employed, using sophisticated commercial solvers for both the VF tissue and glottal airflow domains. The tissue viscoelastic properties were derived from a biphasic formulation. Two cases were considered, whereby the tissue viscoelastic properties corresponded to two different volume fractions of the fluid phase of the VF tissue. For each case, hydrostatic stresses occurring as a result of vibration and collision were investigated. Assuming the VF tissue to be poroelastic, interstitial fluid movement within VF tissue was estimated from the hydrostatic stress gradient. Computed measures of overall VF dynamics (peak airflow velocity, magnitude of VF deformation, frequency of vibration and contact pressure) were well within the range of experimentally observed values. The VF motion leading to mechanical stresses within the VFs and their effect on the interstitial fluid flux is detailed. It is found that average deformation and vibration of VFs tend to increase the state of hydration of the VF tissue, whereas VF collision works to reduce hydration.

Alveolar epithelial cells undergo epithelial-mesenchymal transition in acute interstitial pneumonia: a case report

PubMed Central

2014-01-01

Background Acute interstitial pneumonia is a rare interstitial lung disease that rapidly progresses to respiratory failure or death. Several studies showed that myofibroblast plays an important role in the evolution of diffuse alveolar damage, which is the typical feature of acute interstitial pneumonia. However, no evidence exists whether alveolar epithelial cells are an additional source of myofibroblasts via epithelial-mesenchymal transition in acute interstitial pneumonia. Case presentation In this report, we present a case of acute interstitial pneumonia in a previously healthy 28-year-old non-smoking woman. Chest high-resolution computed tomography scan showed bilateral and diffusely ground-glass opacification. The biopsy was performed on the fifth day of her hospitalization, and results showed manifestation of acute exudative phase of diffuse alveolar damage characterized by hyaline membrane formation. On the basis of the preliminary diagnosis of acute interstitial pneumonia, high-dose glucocorticoid was used. However, this drug showed poor clinical response and could improve the patient’s symptoms only during the early phase. The patient eventually died of respiratory dysfunction. Histological findings in autopsy were consistent with the late form of acute interstitial pneumonia. Conclusions The results in this study revealed that alveolar epithelial cells underwent epithelial-mesenchymal transition and may be an important origin of myofibroblasts in the progression of acute interstitial pneumonia. Conducting research on the transformation of alveolar epithelial cells into myofibroblasts in the lung tissue of patients with acute interstitial pneumonia may be beneficial for the treatment of this disease. However, to our knowledge, no research has been conducted on this topic. PMID:24755111

Volumetric Optical Frequency Domain Imaging of Pulmonary Pathology With Precise Correlation to Histopathology

PubMed Central

Hariri, Lida P.; Applegate, Matthew B.; Mino-Kenudson, Mari; Mark, Eugene J.; Medoff, Benjamin D.; Luster, Andrew D.; Bouma, Brett E.; Tearney, Guillermo J.

2013-01-01

Background: Lung cancer is the leading cause of cancer-related mortality. Radiology and bronchoscopy techniques do not have the necessary resolution to evaluate lung lesions on the microscopic scale, which is critical for diagnosis. Bronchial biopsy specimens can be limited by sampling error and small size. Optical frequency domain imaging (OFDI) provides volumetric views of tissue microstructure at near-histologic resolution and may be useful for evaluating pulmonary lesions to increase diagnostic accuracy. Bronchoscopic OFDI has been evaluated in vivo, but a lack of correlated histopathology has limited the ability to develop accurate image interpretation criteria. Methods: We performed OFDI through two approaches (airway-centered and parenchymal imaging) in 22 ex vivo lung specimens, using tissue dye to precisely correlate imaging and histology. Results: OFDI of normal airway allowed visualization of epithelium, lamina propria, cartilage, and alveolar attachments. Carcinomas exhibited architectural disarray, loss of normal airway and alveolar structure, and rapid light attenuation. Squamous cell carcinomas showed nested architecture. Atypical glandular formation was appreciated in adenocarcinomas, and uniform trabecular gland formation was seen in salivary gland carcinomas. Mucinous adenocarcinomas showed alveolar wall thickening with intraalveolar mucin. Interstitial fibrosis was visualized as signal-dense tissue, with an interstitial distribution in mild interstitial fibrotic disease and a diffuse subpleural pattern with cystic space formation in usual interstitial pneumonitis. Conclusions: To our knowledge, this study is the first demonstration of volumetric OFDI with precise correlation to histopathology in lung pathology. We anticipate that OFDI may play a role in assessing airway and parenchymal pathology, providing fresh insights into the volumetric features of pulmonary disease. PMID:22459781

Systemic amyloidosis: unusual presentation mistaken for a recurrent scabies infection.

PubMed

Haley, Erin M; Nabatian, Adam S; Kopp, Sandra A; Falasca, Gerald F; Haupt, Helen M; Halpern, Analisa V

2014-06-01

We report the case of a 63-year-old woman with a history of undifferentiated connective-tissue disease, polyarthritis, and bilateral carpal tunnel syndrome who presented with generalized pruritus and erythematous and excoriated papules on the trunk and extremities. Empiric scabies treatment was unsuccessful. Patch testing and T-cell receptor gene rearrangement studies were unremarkable. The patient was found to have mild interstitial lung disease and hypogammaglobulinemia. Eventually a diagnosis of primary systemic amyloidosis was made after she developed frank lingual hypertrophy despite normal initial serum protein electrophoresis and negative abdominal fat pad aspiration. Diagnosis was confirmed with lingual biopsy. This case demonstrates an unusual presentation of primary systemic amyloidosis consisting of arthritis and intense debilitating pruritus without primary skin lesions for a full year prior to diagnosis of multiple myeloma. The patient responded to treatment with chemotherapy and corticosteroids.

Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

2007-09-01

Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

Desquamative interstitial pneumonia associated with chrysotile asbestos fibres.

PubMed Central

Freed, J A; Miller, A; Gordon, R E; Fischbein, A; Kleinerman, J; Langer, A M

1991-01-01

The drywall construction trade has in the past been associated with exposure to airborne asbestos fibres. This paper reports a drywall construction worker with 32 years of dust exposure who developed dyspnoea and diminished diffusing capacity, and showed diffuse irregular opacities on chest radiography. He did not respond to treatment with corticosteroids. Open lung biopsy examination showed desquamative interstitial pneumonia. Only a single ferruginous body was seen on frozen section, but tissue examination by electron microscopy showed an extraordinary pulmonary burden of mineral dust with especially high concentrations of chrysotile asbestos fibres. This report emphasises the need to consider asbestos fibre as an agent in the aetiology of desquamative interstitial pneumonia. The coexistent slight interstitial fibrosis present in this case is also considered to have resulted from exposure to mineral dust, particularly ultramicroscopic asbestos fibres. Images PMID:1645584

In vitro developmental model of the gastrointestinal tract from mouse embryonic stem cells.

PubMed

Torihashi, Shigeko; Kuwahara, Masaki; Kurahashi, Masaaki

2007-10-01

Mouse embryonic stem (ES) cells are pluripotent and retain their potential to form cells, tissues and organs originated from three embryonic germ layers. Recently, we developed in vitro organ--gut-like structures--from mouse ES cells. They had basically similar morphological features to a mouse gastrointestinal tract in vivo composed of three distinct layers (i.e., epithelium, connective tissue and musculature). Gut-like structures showed spontaneous contractions derived from pacemaker cells (interstitial cells of Cajal) in the musculature. We also examined their formation process and expression pattern of transcription factors crucial for gut organogenesis such as Id2, Sox17, HNF3beta/Foxa2 and GATA4. We found that they mimic the development of embryonic gut in vivo and showed a similar expression pattern of common transcription factors. They also maintain their developmental potential after transplantation to a renal capsule. Therefore, gut-like structures are suitable for in vitro models of gastrointestinal tracts and their development. In addition, we pointed out several unique features different from gut in vivo that provide useful and advantageous tools to investigate the developmental mechanism of the gastrointestinal tract.

Myodegeneration with fibrosis and regeneration in the pectoralis major muscle of broilers.

PubMed

Sihvo, H-K; Immonen, K; Puolanne, E

2014-05-01

A myopathy affecting the pectoralis major muscle of the commercial broiler has emerged creating remarkable economic losses as well as a potential welfare problem of the birds. We here describe the macroscopic and histologic lesions of this myopathy within 10 pectoralis major muscles of 5- to 6-week-old broilers in Finland. Following macroscopic evaluation and palpation of the muscles, a tissue sample of each was fixed in formalin, processed for histology, and histologically evaluated. The muscles that were macroscopically hard, outbulging, pale, and often accompanied with white striping histologically exhibited moderate to severe polyphasic myodegeneration with regeneration as well as a variable amount of interstitial connective tissue accumulation or fibrosis. All affected cases also exhibited perivenular lymphocyte accumulation. The etiology of this myodegenerative lesion remains yet open. Polyphasic myodegeneration is associated with several previously known etiologies, but palpatory hardness focusing on the pectoralis major, together with perivenular lymphocytes, has not been described in relation to them. The results of this study provide the pathological basis for further studies concerning the etiology of the currently described myopathy.

Near "real" time magnetic resonance images as a monitoring system for interstitial laser therapy: experimental protocols

NASA Astrophysics Data System (ADS)

Castro, Dan J.; Farahani, Keyvan; Soudant, Jacques; Zwarun, Andrew A.; Lufkin, Robert B.

1992-06-01

The failure rate of cancer treatment remains unacceptably high, still being a leading cause of mortality in adults and children despite major advances over the past 50 years in the fields of surgery, radiation therapy and, more recently, chemo and immunotherapy. Surgical access to some deep tumors of the head and neck and other areas often require extensive dissections with residual functional and cosmetic deformities. Repeated treatment is not possible after maximum dose radiotherapy and chemotherapy is still limited by its systemic toxicity. An attractive solution to these problems would be the development of a new adjunctive method combining the best features of interstitial laser therapy for selective tumor destruction via minimally invasive techniques for access and 3-D magnetic resonance imaging (MRI) as a monitoring system for laser-tissue interactions. Interstitial laser therapy (ILT) via fiberoptics allow laser energy to be delivered directly into deeper tissues. However, this concept will become clinically useful only when noninvasive, accurate, and reproducible monitoring methods are developed to measure energy delivery to tissues. MRI has numerous advantages in evaluating the irreversible effects of laser treatment in tissues, since laser energy includes changes not only in the thermal motions of hydrogen protons within the tissue, but also in the distribution and mobility of water and lipids. These techniques should greatly improve the use of ILT in combination with MRI to allow treatment of deeper, more difficult to reach tumors of head and neck and other anatomical areas with a single needle stick.

Bipolar stimulation of a three-dimensional bidomain incorporating rotational anisotropy.

PubMed

Muzikant, A L; Henriquez, C S

1998-04-01

A bidomain model of cardiac tissue was used to examine the effect of transmural fiber rotation during bipolar stimulation in three-dimensional (3-D) myocardium. A 3-D tissue block with unequal anisotropy and two types of fiber rotation (none and moderate) was stimulated along and across fibers via bipolar electrodes on the epicardial surface, and the resulting steady-state interstitial (phi e) and transmembrane (Vm) potentials were computed. Results demonstrate that the presence of rotated fibers does not change the amount of tissue polarized by the point surface stimuli, but does cause changes in the orientation of phi e and Vm in the depth of the tissue, away from the epicardium. Further analysis revealed a relationship between the Laplacian of phi e, regions of virtual electrodes, and fiber orientation that was dependent upon adequacy of spatial sampling and the interstitial anisotropy. These findings help to understand the role of fiber architecture during extracellular stimulation of cardiac muscle.

Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering.

PubMed

Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S

2017-04-01

Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44 + , αSMA + , Vimentin + and CD105 - human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. Copyright © 2016 Elsevier B.V. All rights reserved.

Organization of testicular interstitial tissue of an Australian rodent, the spinifex hopping mouse, Notomys alexis.

PubMed

Peirce, E J; Breed, W G

1990-05-01

The organization of testicular interstitial tissue of the spinifex hopping mouse, Notomys alexis differs from that of other rodents. It comprises between 10.3% and 17.3% (average 15.0%) of the total testicular volume, and is variable in its organization both at different locations within the testis of the one animal and among different individuals. Abundant, closely packed Leydig cells are usually present; however, in some regions large, thick-walled blood vessels and extensive peritubular lymphatic spaces, often lacking an endothelium adjacent to the Leydig cells, are also prominent. The Leydig cells in contact with the large blood vessels and lymphatics, unlike those in regions where lymph is sparse, are not densely packed and sometimes contain numerous lipid droplets. Ultrastructure of Leydig cells is typical of steroid-producing cells; however, mitochondria are often extremely large, unusual in shape or bizarrely arranged in relation to one another. Also electron-dense bodies displaying a paracrystalline-like internal structure of parallel, electron-dense filaments arranged in a lattice pattern occur in the cytoplasm of many cells. The significance of these unusual ultrastructural features and the organization of the interstitial tissue remain to be determined conclusively, but may relate to steroid synthesis, secretion and uptake.

Biopsy in idiopathic pulmonary fibrosis: back to the future.

PubMed

Rossi, Giulio; Spagnolo, Paolo

2017-09-01

Idiopathic Pulmonary Fibrosis (IPF) is a relentlessly progressive, fibrosing interstitial pneumonia characterized by a radiologic and/or histologic pattern of usual interstitial pneumonia (UIP). The availability of two effective anti-fibrotic drugs in IPF has encouraged the identification and treatment of patients in early stages in order to maximize clinical benefit. The ability of high-resolution computed tomography (HRCT) to identify a 'definite' UIP pattern is suboptimal, particularly in the absence of honeycombing. Therefore, radiologic criteria for UIP are currently being redefined. Histology represents the major source of information to define a UIP pattern. Novel and less invasive approaches (particularly cryobiopsy) to sample interstitial lung diseases have demonstrated high sensitivity and specificity. In parallel, researchers are focusing on molecular mechanisms underlying IPF with the aim to identify more specific druggable targets. Lung tissue is therefore essential for diagnostic, pathogenetic and therapeutic purposes. Areas covered: We identified and critically reviewed the most relevant recent literature related to the limitations of current radiologic criteria, new lung sampling procedures, and molecular pathways in support of the need of lung tissue to better understand IPF. Expert commentary: The development of truly effective treatments for IPF requires the identification of key pathogenetic molecules and pathways. To this end, the availability of lung tissue is vital.

Modeling of endoluminal and interstitial ultrasound hyperthermia and thermal ablation: applications to device design, feedback control, and treatment planning

PubMed Central

Prakash, Punit; Salgaonkar, Vasant A.; Diederich, Chris J.

2014-01-01

Endoluminal and catheter-based ultrasound applicators are currently under development and are in clinical use for minimally invasive hyperthermia and thermal ablation of various tissue targets. Computational models play a critical role in in device design and optimization, assessment of therapeutic feasibility and safety, devising treatment monitoring and feedback control strategies, and performing patient-specific treatment planning with this technology. The critical aspects of theoretical modeling, applied specifically to endoluminal and interstitial ultrasound thermotherapy, are reviewed. Principles and practical techniques for modeling acoustic energy deposition, bioheat transfer, thermal tissue damage, and dynamic changes in the physical and physiological state of tissue are reviewed. The integration of these models and applications of simulation techniques in identification of device design parameters, development of real time feedback-control platforms, assessing the quality and safety of treatment delivery strategies, and optimization of inverse treatment plans are presented. PMID:23738697

Amelioration of ischemic brain damage by peritoneal dialysis

PubMed Central

Godino, María del Carmen; Romera, Victor G.; Sánchez-Tomero, José Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, José; Moro, María Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sánchez-Prieto, José

2013-01-01

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients. PMID:23999426

Giant-cell interstitial pneumonia in a gas station worker.

PubMed

Lee, S M; Moon, C H; Oh, Y B; Kim, H Y; Ahn, Y; Ko, E J; Joo, J E

1998-10-01

Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.

Interstitial laser prostatectomy

NASA Astrophysics Data System (ADS)

Johnson, Douglas E.; Cromeens, Douglas M.; Price, Roger E.

1994-05-01

Interstitial laser coagulation of the canine prostate using the Sharplan interstitial thermal therapy fiber (Model 25432) was performed in 9 adult dogs and the subsequent gross and histopathologic changes occurring in the prostate were studied at intervals ranging from 1 hour to 5 weeks. A large well-demarcated area of acute coagulative necrosis developed around each fiber tract which in turn was surrounded by a prominent narrow zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction developed within the coagulative areas within 24 hours and by 4 days, each prostatic lobe contained an irregular cavity which became lined by normal-appearing transitional epithelium and that by 5 weeks, communicated with the prostatic urethra. These changes, similar to those reported following transurethral visual laser ablation of the prostate, suggest that interstitial laser thermal therapy may provide an alternative means for treating selected patients suffering from prostatic enlargement.

Lung and heart pathology in fatal drug addiction. A consecutive autopsy study.

PubMed

Kringsholm, B; Christoffersen, P

1987-01-01

Lung and heart sections from 33 drug addicts submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen were studied together with tissue sections from 20 'normal' persons. In the drug addict cases focal bleedings in lung tissue were found in 94%, signs of earlier bleedings, haemosiderin containing histiocytes, were seen in 91%, and focal fibrosis in 46%. The bleeding episodes may be due to hypoxia in connection with heroin intake. In 94% of the drug addicts birefringent material in lung tissue was demonstrated, in 58% in granulomas and giant cells, in 27% in giant cells only and in 9% in isolated histiocytes. The material was localized in the wall of pulmonar arteries and/or in the interstitial tissue, undoubtedly depending on the duration of the abuse. In 18% angiothrombosis was seen, in all cases granulomas/giant cells were observed in the wall of the vessel concerned. The results indicate periodical intravenous injection of dissolved tablets in addition to heroin. Histological signs of pulmonary hypertension were not seen, possibly due to the fact that abuse of central stimulants is very rare in Denmark. Regarding heart alterations no significant differences were demonstrated between drug addicts and controls. The only note-worthy finding was focal infiltration of lymphocytes in the atrio-ventricular bundle in two drug addicts, the meaning of which is uncertain.

A Computational Study of Systemic Hydration in Vocal Fold Collision

PubMed Central

Bhattacharya, Pinaki; Siegmund, Thomas

2013-01-01

Mechanical stresses develop within vocal fold (VF) soft tissues, due to phonation-associated vibration and collision. These stresses in turn affect the hydration of VF tissue and thus influence voice health. In this paper, high-fidelty numerical computations are described taking into account fully three-dimensional geometry, realistic tissue and air properties, and high-amplitude vibration and collision. A segregated solver approach is employed, using sophisticated commercial solvers for both the VF tissue and glottal airflow domains. The tissue viscoelastic properties were derived from a biphasic formulation. Two cases were considered, whereby the tissue viscoelastic properties corresponded to two different volume fractions of the fluid phase of the VF tissue. For each case, hydrostatic stresses occurring as a result of vibration and collision were investigated. Assuming the VF tissue to be poroelastic, interstitial fluid movement within VF tissue was estimated from the hydrostatic stress gradient. Computed measures of overall VF dynamics (peak air-flow velocity, magnitude of VF deformation, frequency of vibration and contact pressure) were well within the range of experimentally observed values. The VF motion leading to mechanical stresses within the VFs and their effect on the interstitial fluid flux is detailed. It is found that average deformation and vibration of VFs tends to increase the state of hydration of the VF tissue whereas VF collision works to reduce hydration. PMID:23531170

Interstitial assessment of aggressive prostate cancer by physio-chemical photoacoustics: an ex vivo study with intact human prostates.

PubMed

Huang, Shengsong; Qin, Yu; Chen, Yingna; Pan, Jing; Xu, Chengdang; Wu, Denglong; Chao, Wan-Yu; Wei, John T; Tomlins, Scott A; Wang, Xueding; Brian Fowlkes, J; Carson, Paul L; Cheng, Qian; Xu, Guan

2018-06-23

Transrectal ultrasound (TRUS) guided biopsy is the standard procedure for evaluating the presence and aggressiveness of prostate cancer. TRUS biopsy involves tissue removal, and suffers from low core yield as well as high false negative rate. A less invasive and more accurate diagnostic procedure for prostate cancer is therefore highly desired. Combining the optical sensitivity and ultrasonic resolution to resolve the spatial distribution of the major molecular components in tissue, photoacoustic (PA) technology could be an alternative approach for the diagnosis of prostate cancer. The purpose of this study is to examine the feasibility of identifying aggressive prostate cancer using interstitial PA measurements. 17 patients with pre-biopsy magnetic resonance imaging (MRI), TRUS biopsies and planned prostatectomies were enrolled in this study. The interstitial PA measurements were achieved using our recently developed needle PA probe, which was inserted into the ex vivo prostates in the fashion of a biopsy needle. A total of 70 interstitial PA measurements were acquired. The PA measurements were quantified by a previously established PA physio-chemical analysis (PAPCA) method. The histology has confirmed the nonaggressive and aggressive cancerous conditions at the insertion locations. The diagnostic accuracy was also compared to that provided by the pre-biopsy MRI. The quantitative study shows significant differences between the individual parameters of the nonaggressive and the aggressive cancerous regions (p<0.005). Multivariate analysis of the quantitative features achieved a diagnostic accuracy of 78.6% for differentiating nonaggressive and aggressive prostate cancer tissues CONCLUSIONS: The proposed procedure has shown promises in the diagnosis of aggressive prostate cancer. This article is protected by copyright. All rights reserved.

Interstitial ultrasound ablation of tumors within or adjacent to bone: Contributions of preferential heating at the bone surface

NASA Astrophysics Data System (ADS)

Scott, Serena J.; Prakash, Punit; Salgaonkar, Vasant; Jones, Peter D.; Cam, Richard N.; Han, Misung; Rieke, Viola; Burdette, E. Clif; Diederich, Chris J.

2013-02-01

Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters. Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose < 6 CEM43°C and T < 45°C) sensitive structures behind ablated bone. In 3D patient-specific simulations, tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose > 240 CEM43°C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other heating modalities.

Risk of hypersensitivity pneumonitis and interstitial lung diseases among pigeon breeders.

PubMed

Cramer, Christine; Schlünssen, Vivi; Bendstrup, Elisabeth; Stokholm, Zara Ann; Vestergaard, Jesper Medom; Frydenberg, Morten; Kolstad, Henrik Albert

2016-09-01

We studied the risk of hypersensitivity pneumonitis and other interstitial lung diseases (ILDs) among pigeon breeders.This is a retrospective follow-up study from 1980 to 2013 of 6920 pigeon breeders identified in the records of the Danish Racing Pigeon Association. They were compared with 276 800 individually matched referents randomly drawn from the Danish population. Hospital based diagnoses of hypersensitivity pneumonitis and other ILDs were identified in the National Patient Registry 1977-2013. Stratified Cox regression analyses estimated the hazard ratios (HR) of hypersensitivity pneumonitis and other ILDs adjusted for occupation, residence and redeemed prescription of medication with ILDs as a possible side-effect. Subjects were censored at death, emigration or a diagnosis of connective tissue disease.The overall incidence rate of ILD was 77.4 per 100 000 person-years among the pigeon breeders and 50.0 among the referents. This difference corresponded to an adjusted HR of 1.56 (95% CI 1.26-1.94). The adjusted HRs of hypersensitivity pneumonitis and other ILDs for pigeon breeders were 14.36 (95% CI 8.10-25.44) and 1.33 (95% CI 1.05-1.69), respectively.This study shows an increased risk of ILD among pigeon breeders compared with the referent population. Protective measures are recommended even though ILD leading to hospital contact remains rare among pigeon breeders. Copyright ©ERS 2016.

Two-photon laser-generated microtracks in 3D collagen lattices: principles of MMP-dependent and -independent collective cancer cell invasion

NASA Astrophysics Data System (ADS)

Ilina, Olga; Bakker, Gert-Jan; Vasaturo, Angela; Hoffman, Robert M.; Friedl, Peter

2011-02-01

Cancer invasion into an extracellular matrix (ECM) results from a biophysical reciprocal interplay between the expanding cancer lesion and tissue barriers imposed by the adjacent microenvironment. In vivo, connective tissue provides both densely packed ECM barriers adjacent to channel/track-like spaces and loosely organized zones, both of which may impact cancer invasion mode and efficiency; however little is known about how three-dimensional (3D) spaces and aligned tracks present in interstitial tissue guide cell invasion. We here describe a two-photon laser ablation procedure to generate 3D microtracks in dense 3D collagen matrices that support and guide collective cancer cell invasion. Whereas collective invasion of mammary tumor (MMT) breast cancer cells into randomly organized collagen networks required matrix metalloproteinase (MMP) activity for cell-derived collagen breakdown, re-alignment and track generation, preformed tracks supported MMP-independent collective invasion down to a track caliber of 3 µm. Besides contact guidance along the track of least resistance and initial cell deformation (squeezing), MMP-independent collective cell strands led to secondary track expansion by a pushing mechanism. Thus, two-photon laser ablation is useful to generate barrier-free microtracks in a 3D ECM which guide collective invasion independently of pericellular proteolysis.

A comprehensive guide to telocytes and their great potential in cardiovascular system.

PubMed

Kucybala, I; Janas, P; Ciuk, S; Cholopiak, W; Klimek-Piotrowska, W; Holda, M K

2017-01-01

Telocytes, a recently discovered type of interstitial cells, have a very distinctive morphology - the small cell body with long extensions, named telopodes. In our review, apart from introducing general aspects of telocytes, we focus on properties, functions and future potential of those cells in cardiovascular system. However, physiological functions of telocytes in cardiovascular system are still regarded as quite enigmatic. Previous studies claim that they play a role in organogenesis and regeneration, bioelectrical signalling, mechanoelectrical coupling, anti-oxidative protection, angiogenesis and regulation of blood flow. As well, they are presumably connected with the presence of blood-myocardium barrier and proper organisation of extracellular matrix. Moreover, there exists a significant link between the quantity of telocytes in tissue and numerous cardiovascular diseases such as: myocardial infarction, cardiomyopathies, systemic sclerosis, heart failure, atrial fibrillation, isolated atrial amyloidosis, myxomatous valve degeneration and hyperplastic consequences of vascular injury. Thanks to their unique properties, telocytes might be a breakthrough in treatment of cardiovascular diseases, as they may be effective in reversing effects of myocardial infarction. Telocytes also may play a major role in tissue engineering - they might be the key factor in creating stable and efficient vascular network in larger synthetic tissues or organs (Tab. 1, Fig. 3, Ref. 53).

High-power diffusing-tip fibers for interstitial photocoagulation

NASA Astrophysics Data System (ADS)

Sinofsky, Edward L.; Farr, Norman; Baxter, Lincoln; Weiler, William

1997-05-01

A line of optical fiber based diffusing tips has been designed, developed, and tested that are capable of distributing tens of watts of cw laser power over lengths ranging from two millimeters to over 10 cm. The result is a flexible non-stick diffuser capable of coagulating large volumes of tissue in reasonably short exposures of 3 - 5 minutes. Sub-millimeter diameter devices have a distinct effect on reducing the force needed to insert the applicator interstitially into tissue. Utilizing our design approach, we have produced diffusers based on 200 micrometer core fiber that has delivered over 35 watts of Nd:YAG energy over diffusion lengths as short as 4 mm. These applicators are being tested for applications in oncology, cardiology, electrophysiology, urology and gynecology.

Investigations of lymphatic drainage from the interstitial space

NASA Astrophysics Data System (ADS)

Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

2017-11-01

The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

Therapeutic Effects of Human Amniotic Fluid-Derived Stem Cells on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

PubMed Central

Yin, Zhongcheng; Zhou, Xudong; Li, Xiaoju; Xiao, Aiguo

2013-01-01

Interstitial fibrosis is regarded as the main pathway for the progression of chronic kidney disease (CKD) and is often associated with severe renal dysfunction. Stem cell-based therapies may provide alternative approaches for the treatment of CKD. Human amniotic fluid-derived stem cells (hAFSCs) are a novel stem cell population, which exhibit both embryonic and mesenchymal stem cell characteristics. Herein, the present study investigated whether the transplantation of hAFSCs into renal tissues could improve renal interstitial fibrosis in a murine model of unilateral ureteral obstruction (UUO). We showed that hAFSCs provided a protective effect and alleviated interstitial fibrosis as reflected by an increase in microvascular density; additionally, hAFSCs treatment beneficially modulated protein levels of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1). Therefore, we hypothesize that hAFSCs could represent an alternative, readily available source of stem cells that can be applied for the treatment of renal interstitial fibrosis. PMID:23724119

A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration

PubMed Central

Winter, Benjamin J.; O'Connell, Helen E.; Bowden, Scott; Carey, Marcus; Eisen, Damon P.

2015-01-01

Objectives To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. PMID:26325074

Isoflurane in contrast to propofol promotes fluid extravasation during cardiopulmonary bypass in pigs.

PubMed

Brekke, Hege Kristin; Hammersborg, Stig Morten; Lundemoen, Steinar; Mongstad, Arve; Kvalheim, Venny Lise; Haugen, Oddbjørn; Husby, Paul

2013-10-01

A highly positive intraoperative fluid balance should be prevented as it negatively impacts patient outcome. Analysis of volume-kinetics has identified an increase in interstitial fluid volume after crystalloid fluid loading during isoflurane anesthesia. Isoflurane has also been associated with postoperative hypoxemia and may be associated with an increase in alveolar epithelial permeability, edema formation, and hindered oxygen exchange. In this article, the authors compare fluid extravasation rates before and during cardiopulmonary bypass (CPB) with isoflurane- versus propofol-based anesthesia. Fourteen pigs underwent 2 h of tepid CPB with propofol (P-group; n = 7) or isoflurane anesthesia (I-group; n = 7). Fluid requirements, plasma volume, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded, and fluid extravasation rates calculated. Fluid extravasation rates increased in the I-group from the pre-CPB level of 0.27 (0.13) to 0.92 (0.36) ml·kg·min, but remained essentially unchanged in the P-group with significant between-group differences during CPB (pb = 0.002). The results are supported by corresponding changes in interstitial colloid osmotic pressure and total tissue water content. During CPB, isoflurane, in contrast to propofol, significantly contributes to a general increase in fluid shifts from the intravascular to the interstitial space with edema formation and a possible negative impact on postoperative organ function.

Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction.

PubMed

Yan, Qiang; Wang, Baoyao; Sui, Weiguo; Zou, Guimian; Chen, Huaizhou; Xie, Shenping; Zou, Hequn

2012-01-13

To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998.

Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis

PubMed Central

Kullmann, F. Aura; McDonnell, Bronagh M.; Wolf-Johnston, Amanda S.; Lynn, Andrew M.; Getchell, Samuel E.; Ruiz, Wily G.; Zabbarova, Irina V.; Ikeda, Youko; Kanai, Anthony J.; Roppolo, James R.; Bastacky, Sheldon I.; Apodaca, Gerard; Buffington, C. A. Tony; Birder, Lori A.

2018-01-01

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease of unknown etiology. A naturally occurring disease termed feline interstitial cystitis (FIC) reproduces many features of IC/BPS patients. To gain insights into mechanisms underlying IC/BPS, we investigated pathological changes in the lamina propria (LP) of the bladder and proximal urethra in cats with FIC, using histological and molecular methods. Compared to control cat tissue, we found an increased number of de-granulated mast cells, accumulation of leukocytes, increased cyclooxygenase (COX)-1 expression in the bladder LP, and increased COX-2 expression in the urethra LP from cats with FIC. We also found increased suburothelial proliferation, evidenced by mucosal von Brunn’s nests, neovascularization and alterations in elastin content. Scanning electron microscopy revealed normal appearance of the superficial urethral epithelium, including the neuroendocrine cells (termed paraneurons), in FIC urethrae. Together, these histological findings suggest the presence of chronic inflammation of unknown origin leading to tissue remodeling. Since the mucosa functions as part of a “sensory network” and urothelial cells, nerves and other cells in the LP are influenced by the composition of the underlying tissues including the vasculature, the changes observed in the present study may alter the communication of sensory information between different cellular components. This type of mucosal signaling can also extend to the urethra, where recent evidence has revealed that the urethral epithelium is likely to be part of a signaling system involving paraneurons and sensory nerves. Taken together, our data suggest a more prominent role for chronic inflammation and tissue remodeling than previously thought, which may result in alterations in mucosal signaling within the urinary bladder and proximal urethra that may contribute to altered sensations and pain in cats and humans with this syndrome. PMID:29706873

Evaluation of contralateral kidney, liver and lung after extracorporeal shock wave lithotripsy in rabbits.

PubMed

Senyucel, M F; Boybeyi, O; Ayva, S; Aslan, M K; Soyer, T; Demet, A I; Kısa, U; Basar, M; Cakmak, M A

2013-10-01

An experimental study was carried out to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) on contralateral kidney, liver and lung by histopathological and biochemical methods. Twelve New Zealand rabbits were allocated to two groups (n = 6). Tissues of control group (CG, n = 6) were harvested without any intervention. In ESWL group (EG), right kidneys were exposed to 3,000 shock waves at 14 kV energy using electro-hydraulic type ESWL device three times every other day. Both kidneys, liver, and right lobe of lung tissues in EG were harvested on seventh day. Kidneys were examined histopathologically for presence of glomerular and tubular injury, interstitial edema, congestion, inflammation and fibrosis. Livers were examined for hepatocyte vacuolization, congestion, portal inflammation and fibrosis. Lung tissues were examined for loss of normal structure, emphysema, interstitial congestion-edema, prominent alveolar septal vessels, interstitial inflammation, intra-alveolar hemorrhage, intraluminal hemorrhage, peribronchial edema, congestion, inflammation in bronchial wall and epithelial desquamation. Biochemical analysis of tissue samples was performed for oxidative injury markers. Histopathological evaluations revealed that tubular injury was found in both shocked and contralateral kidneys (p < 0.05). EG showed higher grades of portal fibrosis in liver and higher grades of peribronchial congestion in lung when compared to CG (p < 0.05). Biochemical evaluations of both kidneys showed that malondialdehyde levels were higher in EG than in CG (p < 0.05). ESWL causes histopathologic alterations both in shocked and contralateral kidneys. Extrarenal tissues such as liver and lung can be affected by shock waves histopathologically and oxidative injury of contralateral kidney may occur acutely after ESWL.

Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma.

PubMed

Olsson, P Olof; Kalamajski, Sebastian; Maccarana, Marco; Oldberg, Åke; Rubin, Kristofer

2017-01-01

Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.

An analytical poroelastic model for ultrasound elastography imaging of tumors

NASA Astrophysics Data System (ADS)

Tauhidul Islam, Md; Chaudhry, Anuj; Unnikrishnan, Ginu; Reddy, J. N.; Righetti, Raffaella

2018-01-01

The mechanical behavior of biological tissues has been studied using a number of mechanical models. Due to the relatively high fluid content and mobility, many biological tissues have been modeled as poroelastic materials. Diseases such as cancers are known to alter the poroelastic response of a tissue. Tissue poroelastic properties such as compressibility, interstitial permeability and fluid pressure also play a key role for the assessment of cancer treatments and for improved therapies. At the present time, however, a limited number of poroelastic models for soft tissues are retrievable in the literature, and the ones available are not directly applicable to tumors as they typically refer to uniform tissues. In this paper, we report the analytical poroelastic model for a non-uniform tissue under stress relaxation. Displacement, strain and fluid pressure fields in a cylindrical poroelastic sample containing a cylindrical inclusion during stress relaxation are computed. Finite element simulations are then used to validate the proposed theoretical model. Statistical analysis demonstrates that the proposed analytical model matches the finite element results with less than 0.5% error. The availability of the analytical model and solutions presented in this paper may be useful to estimate diagnostically relevant poroelastic parameters such as interstitial permeability and fluid pressure, and, in general, for a better interpretation of clinically-relevant ultrasound elastography results.

Laser Ablatin of Dental Hard Tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seka, W.; Rechmann, P.; Featherstone, J.D.B.

This paper discusses ablation of dental hard tissue using pulsed lasers. It focuses particularly on the relevant tissue and laser parameters and some of the basic ablation processes that are likely to occur. The importance of interstitial water and its phase transitions is discussed in some detail along with the ablation processes that may or may not directly involve water. The interplay between tissue parameters and laser parameters in the outcome of the removal of dental hard tissue is discussed in detail.

The role of nailfold capillaroscopy in interstitial lung diseases - can it differentiate idiopathic cases from collagen tissue disease associated interstitial lung diseases?

PubMed

Çakmakçı Karadoğan, Dilek; Balkarlı, Ayşe; Önal, Özgür; Altınışık, Göksel; Çobankara, Veli

2015-01-01

Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and < 0.001, respectively. This study is to be the first describing and comparing the nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.

Failure to thrive, interstitial lung disease, and progressive digital necrosis with onset in infancy.

PubMed

Chia, Justin; Eroglu, Fehime Kara; Özen, Seza; Orhan, Dicle; Montealegre-Sanchez, Gina; de Jesus, Adriana A; Goldbach-Mansky, Raphaela; Cowen, Edward W

2016-01-01

Key teaching points • SAVI is a recently described interferonopathy resulting from constitutive action of STING and up-regulation of IFN-β signaling. • SAVI is characterized by facial erythema with telangiectasia, acral/cold-sensitive tissue ulceration and amputations, and interstitial lung disease. It has overlapping features with Aicardi-Goutières syndrome and familial chilblain lupus. • Traditional immunosuppressive medications and biologic therapies appear to be of limited benefit, but JAK inhibitors may impact disease progression. Published by Elsevier Inc.

Ultrasound interstitial thermal therapy (USITT) for the treatment of uterine myomas

NASA Astrophysics Data System (ADS)

Nau, William H., Jr.; Diederich, Chris J.; Simko, Jeff; Juang, Titania; Jacoby, Alison; Burdette, E. C.

2007-02-01

Uterine myomas (fibroids) are the most common pelvic tumors occurring in women, and are the leading cause of hysterectomy. Symptoms can be severe, and traditional treatments involve either surgical removal of the uterus (hysterectomy), or the fibroids (myomectomy). Interstitial ultrasound technologies have demonstrated potential for hyperthermia and high temperature thermal therapy in the treatment of benign and malignant tumors. These ultrasound devices offer favorable energy penetration allowing large volumes of tissue to be treated in short periods of time, as well as axial and angular control of heating to conform thermal treatment to a targeted tissue, while protecting surrounding tissues from thermal damage. The goal of this project is to evaluate interstitial ultrasound for controlled thermal coagulation of fibroids. Multi-element applicators were fabricated using tubular transducers, some of which were sectored to produce 180° directional heating patterns, and integrated with water cooling. Human uterine fibroids were obtained after routine myomectomies, and instrumented with thermocouples spaced at 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 cm from the applicator. Power levels ranging from 8-15 W per element were applied for up to 15 minute heating periods. Results demonstrated that therapeutic temperatures >50° C and cytotoxic thermal doses (t 43) extended beyond 2 cm radially from the applicator (>4 cm diameter). It is anticipated that this system will make a significant contribution toward the treatment of uterine fibroids.

MRI-Based Computational Model of Heterogeneous Tracer Transport following Local Infusion into a Mouse Hind Limb Tumor

PubMed Central

Magdoom, Kulam Najmudeen; Pishko, Gregory L.; Rice, Lori; Pampo, Chris; Siemann, Dietmar W.; Sarntinoranont, Malisa

2014-01-01

Systemic drug delivery to solid tumors involving macromolecular therapeutic agents is challenging for many reasons. Amongst them is their chaotic microvasculature which often leads to inadequate and uneven uptake of the drug. Localized drug delivery can circumvent such obstacles and convection-enhanced delivery (CED) - controlled infusion of the drug directly into the tissue - has emerged as a promising delivery method for distributing macromolecules over larger tissue volumes. In this study, a three-dimensional MR image-based computational porous media transport model accounting for realistic anatomical geometry and tumor leakiness was developed for predicting the interstitial flow field and distribution of albumin tracer following CED into the hind-limb tumor (KHT sarcoma) in a mouse. Sensitivity of the model to changes in infusion flow rate, catheter placement and tissue hydraulic conductivity were investigated. The model predictions suggest that 1) tracer distribution is asymmetric due to heterogeneous porosity; 2) tracer distribution volume varies linearly with infusion volume within the whole leg, and exponentially within the tumor reaching a maximum steady-state value; 3) infusion at the center of the tumor with high flow rates leads to maximum tracer coverage in the tumor with minimal leakage outside; and 4) increasing the tissue hydraulic conductivity lowers the tumor interstitial fluid pressure and decreases the tracer distribution volume within the whole leg and tumor. The model thus predicts that the interstitial fluid flow and drug transport is sensitive to porosity and changes in extracellular space. This image-based model thus serves as a potential tool for exploring the effects of transport heterogeneity in tumors. PMID:24619021

The multiple faces of leukocyte interstitial migration

PubMed Central

Lämmermann, Tim; Germain, Ronald N.

2014-01-01

Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments. PMID:24573488

Theoretical comparison of two interstitial ultrasound applicators designed to induce cylindrical zones of tissue ablation.

PubMed

Lafon, C; Chavrier, F; Prat, F; Chapelon, J Y; Cathignol, D

1999-05-01

Although interstitial techniques are invasive, they are still the first-line therapeutic modalities for certain types of tumour. They are mainly relevant to tumours that are either inoperable or located so deep that access is complicated. Of the various types of radiation that can be delivered by the interstitial route, ultrasound is the most suitable for deep heating. The study compares the efficacy of two types of applicator with respect to their ability to induce cylindrical zones of coagulation necrosis. The transducer of the first applicator is tubular, whereas the second is plane and can rotate around its axis. Both have an external diameter of 4 mm, are fitted with surface cooling systems and operate at 10.7 MHz and 14 W.cm-2. Comparison involves mathematical modelling of ablated tissue in the targeted area by resolving the bioheat transfer equation (BHTE) using an algorithm based on finite differences. The BHTE gives a temperature value from which the thermal dose can be determined. It is shown that tissue ablation by tubular transducers is slow, and, in consequence, perfusion disturbs the heating pattern: in vivo, irradiation with a tubular transducer lasting 1081 s would be required to ablate a tissue mass with a radius of 8 mm. The corresponding period using a rotating plane transducer with 20 firing angles is only 618 s. The mean exposure time of each shot lasts 31 +/- 7 s. Therefore perfusion would have much less impact in the case of therapy administered using a plane transducer than that using a tubular one.

Increased matrix metalloproteinases as possible cause of osseoarticular tissue destruction in long-term haemodialysis and beta 2-microglobulin amyloidosis.

PubMed

Ohashi, K; Kawai, R; Hara, M; Okada, Y; Tachibana, S; Ogura, Y

1996-04-01

Immunolocalization of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in periarticular tissues of beta 2-microglobulin amyloidosis patients was investigated. MMP-1 (interstitial collagenase) the most strongly expressed of the MMPs, was localized in the synovial lining cells, mesenchymal cells in granulation tissue and nodular amyloid deposits, and chondrocytes within areas of cartilage erosion. Expression of MMP-1 was correlated with the degree of macrophage infiltration and synovial cell hyperplasia, but it was not correlated with the degree of amyloid deposition or haemodialysis period. Expression of MMP-1 appeared more intense than that of TIMP-1 and TIMP-2 in highly inflammatory cases. MMP-2 was mildly expressed in the interstitial fibroblasts and MMP-3 was faintly stained in the extracellular matrix of the synovial membrane. MMP-9 (gelatinase B) was found to be strongly positive in the osteoclasts which increased in the progressing osteolytic lesion from the destructive arthropathy. These results suggest involvement of MMPs in inflammation with an imbalance between expression of MMPs and TIMPs being closely related to pathogenesis of the destructive arthropathy.

Pulsed-High Intensity Focused Ultrasound (HIFU) Exposures for Enhanced Delivery of Therapeutics: Mechanisms and Applications

NASA Astrophysics Data System (ADS)

Frenkel, Victor; Deng, Cheri; O'Neill, Brian E.; Quijano, Jade; Stone, Michael J.; Dromi, Sergio; Hunter, Finie; Xie, Jianwu; Quinn, Timothy P.; Wood, Bradford J.; Li, King C. P.

2006-05-01

The majority of focused ultrasound applications today involve long, continuous exposures that produce significant temperature elevations for tissue ablation and irreversible coagulative necrosis. Comparatively little has been done with non-continuous (or, pulsed) exposures that can produce primarily mechanical effects with only minimal heat. Our investigations have shown that pulsed-HIFU exposures can non-invasively and non-destructively enhance the delivery of both systemically and locally injected materials (e.g. imaging agents, optical probes, and plasmid DNA) in both normal and cancerous tissues. It is hypothesized that the enhancing effects are directly linked to tissue displacement from locally-generated radiation forces. In normal tissue, it is thought that shear forces are produced between adjacent tissue regions experiencing non-uniform displacement. The resulting strain opens cellular junctions in both the vasculature and the parenchyma, increasing extravasation and interstitial diffusion, respectively. In solid tumors, improved delivery is thought to also be related to both an increase in fluid exchange that leads to decreased interstitial pressure, and disruptions of fibrillar collagen in the extracellular matrix. Preliminary experiments are presented that were carried out to help elucidate the mechanisms by which enhanced delivery was achieved, and possible directions for future investigations are discussed.

Development of a 3D patient-specific planning platform for interstitial and transurethral ultrasound thermal therapy

NASA Astrophysics Data System (ADS)

Prakash, Punit; Diederich, Chris J.

2010-03-01

Interstitial and transurethral catheter-based ultrasound devices are under development for treatment of prostate cancer and BPH, uterine fibroids, liver tumors and other soft tissue disease. Accurate 3D thermal modeling is essential for designing site-specific applicators, exploring treatment delivery strategies, and integration of patient-specific treatment planning of thermal ablations. We are developing a comprehensive 3D modeling and treatment planning platform for ultrasound ablation of tissue using catheter-based applicators. We explored the applicability of assessing thermal effects in tissue using critical temperature, thermal dose and Arrhenius thermal damage thresholds and performed a comparative analysis of dynamic tissue properties critical to accurate modeling. We used the model to assess the feasibility of automatic feedback control with MR thermometry, and demonstrated the utility of the modeling platform for 3D patient-specific treatment planning. We have identified critical temperature, thermal dose and thermal damage thresholds for assessing treatment endpoint. Dynamic changes in tissue attenuation/absorption and perfusion must be included for accurate prediction of temperature profiles and extents of the ablation zone. Lastly, we demonstrated use of the modeling platform for patient-specific treatment planning.

Dermal Collagen and Lipid Deposition Correlate with Tissue Swelling and Hydraulic Conductivity in Murine Primary Lymphedema

PubMed Central

Rutkowski, Joseph M.; Markhus, Carl Erik; Gyenge, Christina C.; Alitalo, Kari; Wiig, Helge; Swartz, Melody A.

2010-01-01

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling—predominantly collagen and fat deposition—may dictate tissue swelling and govern interstitial transport in lymphedema. PMID:20110415

Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema.

PubMed

Rutkowski, Joseph M; Markhus, Carl Erik; Gyenge, Christina C; Alitalo, Kari; Wiig, Helge; Swartz, Melody A

2010-03-01

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling--predominantly collagen and fat deposition--may dictate tissue swelling and govern interstitial transport in lymphedema.

Herpes virus infection associated with interstitial nephritis in a beaked whale (Mesoplodon densirostris)

PubMed Central

2012-01-01

Background The capacity for herpesvirus to cause disease in cetaceans is unclear and may be varied depending on the different conditions of individuals and between different species. Kidney pathology and intralesional virus-associated infection have been rarely reported in cetaceans. Result On April 2004, an old adult male Blainville’s beaked whale (Mesoplodon densirostris) 420 cm long with a poor body condition was stranded on Tenerife Island. During necropsy, no gross lesions were observed in the kidneys. However, membranous glomerulonephritis, multifocal interstitial lymphoplasmacytic nephritis and acute multifocal necrotizing tubulointerstitial nephritis with intranuclear inclusion bodies was diagnosed by histological analysis. Tissue samples were submitted for bacteriological analysis and molecular viral screening. Conclusion A novel alpha herpesvirus associated with interstitial nephritis was identified in an old adult male Blainville's beaked whale (M. densirostris) with a poor body condition stranded in the Canary Islands. This report suggests that identification of herpesvirus infection could be used as a differential diagnosis for interstitial nephritis in cetaceans. PMID:23237059

A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

NASA Astrophysics Data System (ADS)

Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

1995-10-01

Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

Progression of renal fibrosis in congenital CKD model rats with reduced number of nephrons.

PubMed

Yasuda, Hidenori; Tochigi, Yuki; Katayama, Kentaro; Suzuki, Hiroetsu

2017-06-14

A congenital reduction in the number of nephrons is a critical risk factor for both onset of chronic kidney disease (CKD) and its progression to end-stage kidney disease (ESKD). Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and show progressive CKD. This study used an immunohistological method to assess glomerular and interstitial pathogenesis in male HPK rats aged 35-210days. CD68 positive-macrophages were found to infiltrate into glomeruli in HPK rats aged 35 and 70days and to infiltrate into interstitial tissue in rats aged 140 and 210days. HPK rats aged 35 and 70days showed glomerular hypertrophy, loss of normal linear immunostaining of podocine, and increased expression of PDGFr-β, TGF-β, collagens, and fibronectin, with all of these alterations gradually deteriorating with age. α-SMA-positive myofibroblasts were rarely detected in glomerular tufts, whereas α-SMA-positive glomerular parietal epithelium (GPE) cells were frequently observed along Bowman's capsular walls. The numbers of PDGFr-β-positive fibroblasts in interstitial tissue were increased in rats aged 35days and older, whereas interstitial fibrosis, characterized by the increased expression of tubular PDGF-BB, the appearance of myofibroblasts doubly positive for PDGFr-β and α-SMA, and increased expression of collagens and fibronectin, were observed in rats aged 70 and older. These results clearly indicate that congenital CKD with only 20% of nephrons cause renal fibrosis in rats. Copyright © 2017 Elsevier GmbH. All rights reserved.

Textural versus electrostatic exclusion-enrichment effects in the effective chemical transport within the cortical bone: a numerical investigation.

PubMed

Lemaire, T; Kaiser, J; Naili, S; Sansalone, V

2013-11-01

Interstitial fluid within bone tissue is known to govern the remodelling signals' expression. Bone fluid flow is generated by skeleton deformation during the daily activities. Due to the presence of charged surfaces in the bone porous matrix, the electrochemical phenomena occurring in the vicinity of mechanosensitive bone cells, the osteocytes, are key elements in the cellular communication. In this study, a multiscale model of interstitial fluid transport within bone tissues is proposed. Based on an asymptotic homogenization method, our modelling takes into account the physicochemical properties of bone tissue. Thanks to this multiphysical approach, the transport of nutrients and waste between the blood vessels and the bone cells can be quantified to better understand the mechanotransduction of bone remodelling. In particular, it is shown that the electrochemical tortuosity may have stronger implications in the mass transport within the bone than the purely morphological one. Copyright © 2013 John Wiley & Sons, Ltd.

Fluid resuscitation following a burn injury: implications of a mathematical model of microvascular exchange.

PubMed

Bert, J; Gyenge, C; Bowen, B; Reed, R; Lund, T

1997-03-01

A validated mathematical model of microvascular exchange in thermally injured humans has been used to predict the consequences of different forms of resuscitation and potential modes of action of pharmaceuticals on the distribution and transport of fluid and macromolecules in the body. Specially, for 10 and/or 50 per cent burn surface area injuries, predictions are presented for no resuscitation, resuscitation with the Parkland formula (a high fluid and low protein formulation) and resuscitation with the Evans formula (a low fluid and high protein formulation). As expected, Parkland formula resuscitation leads to interstitial accumulation of excess fluid, while use of the Evans formula leads to interstitial accumulation of excessive amounts of proteins. The hypothetical effects of pharmaceuticals on the transport barrier properties of the microvascular barrier and on the highly negative tissue pressure generated postburn in the injured tissue were also investigated. Simulations predict a relatively greater amelioration of the acute postburn edema through modulation of the postburn tissue pressure effects.

Interstitial Matrix Prevents Therapeutic Ultrasound From Causing Inertial Cavitation in Tumescent Subcutaneous Tissue.

PubMed

Koulakis, John P; Rouch, Joshua; Huynh, Nhan; Dubrovsky, Genia; Dunn, James C Y; Putterman, Seth

2018-01-01

We search for cavitation in tumescent subcutaneous tissue of a live pig under application of pulsed, 1-MHz ultrasound at 8 W cm -2 spatial peak and pulse-averaged intensity. We find no evidence of broadband acoustic emission indicative of inertial cavitation. These acoustic parameters are representative of those used in external-ultrasound-assisted lipoplasty and in physical therapy and our null result brings into question the role of cavitation in those applications. A comparison of broadband acoustic emission from a suspension of ultrasound contrast agent in bulk water with a suspension injected subcutaneously indicates that the interstitial matrix suppresses cavitation and provides an additional mechanism behind the apparent lack of in-vivo cavitation to supplement the absence of nuclei explanation offered in the literature. We also find a short-lived cavitation signal in normal, non-tumesced tissue that disappears after the first pulse, consistent with cavitation nuclei depletion in vivo. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

PubMed

Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

2010-10-01

In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular) interstitial neurons in the postnatal and adult deep cerebral white matter (i.e. corpus callosum, anterior commissure, internal and external capsule and the corona radiata/centrum semiovale). Although these deep interstitial neurons are poorly developed or absent in the brains of rodents, they represent a prominent feature of the significantly enlarged white matter of human and non-human primate brains. © 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland.

Interstitial Glucose and Physical Exercise in Type 1 Diabetes: Integrative Physiology, Technology, and the Gap In-Between

PubMed Central

Moser, Othmar; Yardley, Jane E.; Bracken, Richard M.

2018-01-01

Continuous and flash glucose monitoring systems measure interstitial fluid glucose concentrations within a body compartment that is dramatically altered by posture and is responsive to the physiological and metabolic changes that enable exercise performance in individuals with type 1 diabetes. Body fluid redistribution within the interstitial compartment, alterations in interstitial fluid volume, changes in rate and direction of fluid flow between the vasculature, interstitium and lymphatics, as well as alterations in the rate of glucose production and uptake by exercising tissues, make for caution when interpreting device read-outs in a rapidly changing internal environment during acute exercise. We present an understanding of the physiological and metabolic changes taking place with acute exercise and detail the blood and interstitial glucose responses with different forms of exercise, namely sustained endurance, high-intensity, and strength exercises in individuals with type 1 diabetes. Further, we detail novel technical information on currently available patient devices. As more health services and insurance companies advocate their use, understanding continuous and flash glucose monitoring for its strengths and limitations may offer more confidence for patients aiming to manage glycemia around exercise. PMID:29342932

Limitations of the permeability-limited compartment model in estimating vascular permeability and interstitial volume fraction in DCE-MRI.

PubMed

Carreira, Guido Correia; Gemeinhardt, Ole; Gorenflo, Rudolf; Beyersdorff, Dirk; Franiel, Tobias; Plendl, Johanna; Lüdemann, Lutz

2011-06-01

Dynamic contrast-enhanced magnetic resonance imaging commonly uses compartment models to estimate tissue parameters in general and perfusion parameters in particular. Compartment models assume a homogeneous distribution of the injected tracer throughout the compartment volume. Since tracer distribution within a compartment cannot be assessed, the parameters obtained by means of a compartment model might differ from the actual physical values. This work systematically examines the widely used permeability-surface-limited one-compartment model to determine the reliability of the parameters obtained by comparing them with their actual values. A computer simulation was used to model spatial tracer distribution within the interstitial volume using diffusion of contrast agent in tissue. Vascular parameters were varied as well as tissue parameters. The vascular parameters used were capillary radius (4 and 12 μm), capillary permeability (from 0.03 to 3.3 μm/s) and intercapillary distances from 30 to 300 μm. The tissue parameters used were tortuosity (λ), porosity (α) and interstitial volume fraction (v(e)). Our results suggest that the permeability-surface-limited compartment model generally underestimates capillary permeability for capillaries with a radius of 4 μm by factors from ≈0.03 for α=0.04, to ≈ 0.1 for α=0.2, to ≈ 0.5 for α=1.0. An overestimation of actual capillary permeability for capillaries with a radius of 12 μm by a factor of ≥1.3 was found for α=1.0, while α=0.2 yielded an underestimation by a factor of ≈0.3 and α=0.04 by a factor of ≈ 0.03. The interstitial volume fraction, v(e), obtained by the compartment model differed with increasing intercapillary distances and for low vessel permeability, whereas v(e) was found to be estimated approximately accurately for P=0.3 μm/s and P=3.3 μm/s for vessel distances <100 μm. Copyright © 2011 Elsevier Inc. All rights reserved.

Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung diseases*

PubMed Central

Yamada, Tsutomu; Kawabata, Yoshinori

2015-01-01

Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs). Histological markers of pneumocyte injury and inflammation include pneumocyte necrosis, erosion, hyaline membrane and fibrin exudation with subsequent intraluminal granulation tissue formation. We found that intracytoplasmic inclusions in pneumocytes are ubiquitin-positive (Ub+) and that the number of Ub+ pneumocytes shows positive correlation with the extent of diffuse alveolar damage (DAD). To determine the role of Ub+ pneumocytes and inclusions in IPs, we studied their relationship with pathological and clinical features of DAD, usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including airspace enlargement with fibrosis (AEF). We analysed Ub+ pneumocytes, inclusions, erosions and intraluminal granulation tissue in relation to pneumocyte injury. The numbers of immunohistochemically identified Ub+ inclusions in each IP were higher than the number of inclusions detected by light microscopy. The inclusions detected by Ub+ immunostaining were identical to the inclusions observed by light microscopy. UIP and DAD had many Ub+ inclusions, while OP and AEF had fewer Ub+ inclusions. These results suggest that the extent of Ub+ inclusions reflects the severity of pneumocyte injury among IPs. Thus, Ub+ inclusions are a histological marker of pneumocyte injury that may be helpful in determining the severity and prognosis of IPs. PMID:25123224

Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies.

PubMed

Hukkanen, V; Haarala, M; Nurmi, M; Klemi, P; Kiilholma, P

1996-01-01

Microbes may be involved in the pathogenesis of interstitial cystitis (IC). Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder and they are causative agents for hemorrhagic cystitis. We therefore studied the presence of adenovirus and BKV genomes in urinary bladder tissue specimens of patients with IC using polymerase chain reaction (PCR) and in situ hybridization (ISH). Controls were specimens from cases with transitional cell carcinoma of the bladder. Nucleic acids were extracted from paraffin sections of the bladder tissue for PCR. Primers detecting all adenovirus types were used. In situ hybridization was carried out for the paraffin sections using digoxigenin-labeled DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one to two infected cells/specimen. All the seven IC cases studied and six controls were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was also considered negative in IC cases and controls. The specimens which were negative in PCR tests yielded a signal with beta-globin primers, thus being amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic role in interstitial cystitis.

Case-based lung image categorization and retrieval for interstitial lung diseases: clinical workflows.

PubMed

Depeursinge, Adrien; Vargas, Alejandro; Gaillard, Frédéric; Platon, Alexandra; Geissbuhler, Antoine; Poletti, Pierre-Alexandre; Müller, Henning

2012-01-01

Clinical workflows and user interfaces of image-based computer-aided diagnosis (CAD) for interstitial lung diseases in high-resolution computed tomography are introduced and discussed. Three use cases are implemented to assist students, radiologists, and physicians in the diagnosis workup of interstitial lung diseases. In a first step, the proposed system shows a three-dimensional map of categorized lung tissue patterns with quantification of the diseases based on texture analysis of the lung parenchyma. Then, based on the proportions of abnormal and normal lung tissue as well as clinical data of the patients, retrieval of similar cases is enabled using a multimodal distance aggregating content-based image retrieval (CBIR) and text-based information search. The global system leads to a hybrid detection-CBIR-based CAD, where detection-based and CBIR-based CAD show to be complementary both on the user's side and on the algorithmic side. The proposed approach is in accordance with the classical workflow of clinicians searching for similar cases in textbooks and personal collections. The developed system enables objective and customizable inter-case similarity assessment, and the performance measures obtained with a leave-one-patient-out cross-validation (LOPO CV) are representative of a clinical usage of the system.

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.

PubMed Central

Lilge, L.; Olivo, M. C.; Schatz, S. W.; MaGuire, J. A.; Patterson, M. S.; Wilson, B. C.

1996-01-01

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8562339

Dual modal endoscopic cancer detection based on optical pH sensing and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Kim, Soogeun; Kim, ByungHyun; Sohn, Won Bum; Byun, Kyung Min; Lee, Soo Yeol

2017-02-01

To discriminate between normal and cancerous tissue, a dual modal approach using Raman spectroscopy and pH sensor was designed and applied. Raman spectroscopy has demonstrated the possibility of using as diagnostic method for the early detection of precancerous and cancerous lesions in vivo. It also can be used in identifying markers associated with malignant change. However, Raman spectroscopy lacks sufficient sensitivity due to very weak Raman scattering signal or less distinctive spectral pattern. A dual modal approach could be one of the solutions to solve this issue. The level of extracellular pH in cancer tissue is lower than that in normal tissue due to increased lactic acid production, decreased interstitial fluid buffering and decreased perfusion. High sensitivity and specificity required for accurate cancer diagnosis could be achieved by combining the chemical information from Raman spectrum with metabolic information from pH level. Raman spectra were acquired by using a fiber optic Raman probe, a cooled CCD camera connected to a spectrograph and 785 nm laser source. Different transmission spectra depending on tissue pH were measured by a lossy-mode resonance sensor based on fiber optic. The discriminative capability of pH-Raman dual modal method was evaluated using principal component analysis (PCA). The obtained results showed that the pH-Raman dual modal approach can improve discriminative capability between normal and cancerous tissue, which can lead to very high sensitivity and specificity. The proposed method for cancer detection is expected to be used in endoscopic diagnosis later.

Diseases and disorders of muscle.

PubMed

Pearson, A M; Young, R B

1993-01-01

Muscle may suffer from a number of diseases or disorders, some being fatal to humans and animals. Their management or treatment depends on correct diagnosis. Although no single method may be used to identify all diseases, recognition depends on the following diagnostic procedures: (1) history and clinical examination, (2) blood biochemistry, (3) electromyography, (4) muscle biopsy, (5) nuclear magnetic resonance, (6) measurement of muscle cross-sectional area, (7) tests of muscle function, (8) provocation tests, and (9) studies on protein turnover. One or all of these procedures may prove helpful in diagnosis, but even then identification of the disorder may not be possible. Nevertheless, each of these procedures can provide useful information. Among the most common diseases in muscle are the muscular dystrophies, in which the newly identified muscle protein dystrophin is either absent or present at less than normal amounts in both Duchenne and Becker's muscular dystrophy. Although the identification of dystrophin represents a major breakthrough, treatment has not progressed to the experimental stage. Other major diseases of muscle include the inflammatory myopathies and neuropathies. Atrophy and hypertrophy of muscle and the relationship of aging, exercise, and fatigue all add to our understanding of the behavior of normal and abnormal muscle. Some other interesting related diseases and disorders of muscle include myasthenia gravis, muscular dysgenesis, and myclonus. Disorders of energy metabolism include those caused by abnormal glycolysis (Von Gierke's, Pompe's, Cori-Forbes, Andersen's, McArdle's, Hers', and Tauri's diseases) and by the acquired diseases of glycolysis (disorders of mitochondrial oxidation). Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic periodic paralysis, and malignant hyperexia). Diseases of the connective tissues discussed include those of nutritional origin (scurvy, lathyrism, starvation, and protein deficiency), the genetic diseases (dermatosparaxis, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, homocystinuria, alcaptonuria, epidermolysis bullosa, rheumatoid arthritis in humans, polyarthritis in swine, Aleutian disease of mink, and the several types of systemic lupus erythematosus) and the acquired diseases of connective tissues (abnormal calcification, systemic sclerosis, interstitial lung disease, hepatic fibrosis, and carcinomas of the connective tissues). Several of the diseases of connective tissues may prove to be useful models for determining the relationship of collagen to meat tenderness and its other physical properties. Several other promising models for studying the nutrition-related disorders and the quality-related characteristics of meat are also reviewed.

Significance of myositis autoantibody in patients with idiopathic interstitial lung disease.

PubMed

Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo; Kang, Eun-Suk

2015-05-01

Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We analyzed a panel of 11 myositis autoantibody specificities in the patients using a line blot immunoassay. Then, we divided them into myositis autoantibody-positive and -negative groups and compared the clinical features and laboratory data between the two groups. Of the 32 idiopathic ILD patients, 12 patients had myositis autoantibodies encompassing 9 specificities, except for anti-Mi-2 and anti-PM-Scl 100 (12/32, 38%). Anti-synthetase autoantibodies including Jo-1, EJ, OJ, PL-7, and PL-12 were present in 7 patients (7/32, 22%). The group with myositis autoantibodies presented more frequently with the symptom of mechanic's hand and showed abnormal pulmonary function test results with low forced vital capacity, diffusing capacity for carbon monoxide, total lung capacity, and high lactate dehydrogenase values in blood when compared with the group without myositis antibodies. We strongly suggest that patients undergo an evaluation of myositis autoantibodies, if they are diagnosed with idiopathic ILD in the presence of clinical characteristics including mechanic's hand, arthralgia, and autoantibodies which are insufficient to make a diagnosis of a specific CTD category.

Sapphire capillary interstitial irradiators for laser medicine

NASA Astrophysics Data System (ADS)

Shikunova, I. A.; Dolganova, I. N.; Dubyanskaya, E. N.; Mukhina, E. E.; Zaytsev, K. I.; Kurlov, V. N.

2018-04-01

In this paper, we demonstrate instruments for laser radiation delivery based on sapphire capillary needles. Such sapphire irradiators (introducers) can be used for various medical applications, such as photodynamic therapy, laser hyperthermia, laser interstitial thermal therapy, and ablation of tumors of various organs. Unique properties of sapphire allow for effective redistribution of the heat, generated in biological tissues during their exposure to laser radiation. This leads to homogeneous distribution of the laser irradiation around the needle, and lower possibility of formation of the overheating focuses, as well as the following non-transparent thrombi.

Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment.

PubMed

Khalil, Nasreen; O'Connor, Robert

2004-07-20

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.

In vivo determination of steric and electrostatic exclusion of albumin in rat skin and skeletal muscle

PubMed Central

Gyenge, Christina C; Tenstad, Olav; Wiig, Helge

2003-01-01

In order to estimate the magnitude of electrostatic exclusion provided by the fixed negative charges of the skin and muscle interstitia of rat in vivo we measured the distribution volumes of two differently charged albumin probes within these tissues. An implanted osmotic pump was used to reach and maintain a steady-state extracellular concentration of a mixture containing two iodine-labelled probes: a charged-modified human serum albumin, cHSA (i.e. a positive probe, isoelectirc point (pI) = 7.6) and a native human serum albumin, HSA (i.e. a normally charged, negative probe, pI = 5.0). Steady-state tissue concentrations were achieved after intravenous infusion of probes for 5–7 days. At the end of this period the animals were nephrectomized and a bolus of 51Cr-EDTA was administered for estimating the extracellular volume. Plasma volumes were measured as 5-min distribution volume of 125I-HSA in separate experiments. The steady-state interstitial fluid concentrations of all probes were determined using nylon wicks implanted postmortem. Calculations of labelled probes were made for interstitial fluid volumes (Vi), extravascular albumin distribution volumes (Vav,a) and relative interstitial excluded volume fractions (Vex,a/Vi). We found that the positive probe is excluded from a significantly smaller fraction of the interstitium. Specifically, the average relative albumin exclusion fractions obtained were: 16% and 26% in skeletal muscle and 30% and 40% in skin, for cHSA and HSA, respectively. On average, the fixed negative charges of the interstitium are responsible for about 40% of the total albumin exclusion in skeletal muscle and 25% in the whole skin tissue and thus, contribute significantly to volume exclusion in these tissues. PMID:12937287

In vivo determination of steric and electrostatic exclusion of albumin in rat skin and skeletal muscle.

PubMed

Gyenge, Christina C; Tenstad, Olav; Wiig, Helge

2003-11-01

In order to estimate the magnitude of electrostatic exclusion provided by the fixed negative charges of the skin and muscle interstitia of rat in vivo we measured the distribution volumes of two differently charged albumin probes within these tissues. An implanted osmotic pump was used to reach and maintain a steady-state extracellular concentration of a mixture containing two iodine-labelled probes: a charged-modified human serum albumin, cHSA (i.e. a positive probe, isoelectirc point (pI) = 7.6) and a native human serum albumin, HSA (i.e. a normally charged, negative probe, pI = 5.0). Steady-state tissue concentrations were achieved after intravenous infusion of probes for 5-7 days. At the end of this period the animals were nephrectomized and a bolus of 51Cr-EDTA was administered for estimating the extracellular volume. Plasma volumes were measured as 5-min distribution volume of 125I-HSA in separate experiments. The steady-state interstitial fluid concentrations of all probes were determined using nylon wicks implanted postmortem. Calculations of labelled probes were made for interstitial fluid volumes (Vi), extravascular albumin distribution volumes (Vav,a) and relative interstitial excluded volume fractions (Vex,a/Vi). We found that the positive probe is excluded from a significantly smaller fraction of the interstitium. Specifically, the average relative albumin exclusion fractions obtained were: 16% and 26% in skeletal muscle and 30% and 40% in skin, for cHSA and HSA, respectively. On average, the fixed negative charges of the interstitium are responsible for about 40% of the total albumin exclusion in skeletal muscle and 25% in the whole skin tissue and thus, contribute significantly to volume exclusion in these tissues.

Ulinastatin inhibits renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction.

PubMed

Zhang, Qing-Fang

2017-12-01

The effect of ulinastatin (UTI) on renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) was investigated. A total of 18 male Wistar rats were randomly divided into the following 3 groups: The Sham group (n=6), the UUO group (n=6), and the UTI group (n=6). In the UUO and UTI groups, the left ureter was ligated to establish a UUO model. Starting from day 1 after surgery, an intervention treatment was performed using normal saline (1 ml/kg/d) and UTI (40,000 unit/kg/d). On day 7 after surgery, 6 rats from each group were sacrificed. In the Sham group, the left ureter was only freed, not ligated; after 7 days of abdominal closure, all of the rats were sacrificed. Blood samples were collected prior to sacrificing the animals to measure the blood urea nitrogen (BUN) and serum creatinine (Scr). The incidence of renal interstitial lesions on the obstruction side was observed by hematoxylin and eosin, and Masson staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical detection of apoptosis regulator Bax (Bax), apoptosis regulator Bcl‑2 (Bcl‑2) and caspase‑3 were performed to observe the presence of renal tubular epithelial cell apoptosis. The UTI did not have a significant influence on the mouse BUN and Scr levels in any of the groups (P>0.05). Compared with that in the Sham group, renal tissue injury in the UUO group was significantly aggravated with renal tubular dilation, epithelial cell atrophy, renal interstitial inflammatory cell infiltration and fibrous tissue hyperplasia (P<0.01). Furthermore, the renal tubular epithelial TUNEL+ cell number and Bax and caspase‑3 levels were increased, and the expression of Bcl‑2 was decreased (P<0.01). Following the UTI treatment, the renal interstitial injury at the obstruction side was significantly attenuated (P<0.05), the renal tubular epithelial TUNEL+ cell number, and Bax and caspase‑3 levels significantly decreased, and the expression of Bcl‑2 was restored (P<0.05). UTI inhibited renal tubular epithelial apoptosis and interstitial fibrosis in UUO rats.

[Human joint capsule in osteoarthrosis (morpholocical changes) (author's transl)].

PubMed

Dettmer, N; Barz, B

1977-07-29

Morphological investigations of the joint capsules in osteoarthrotic-changed joints have given rise to doubts about the present theory of the causal aetiology of the osteoarthrosis. In every inspected and demonstrated illustration beside the partly normal capsules segments could be found every transition between mild regressive alterations and most massive proliferative changes of the conective tissue and the lining cell layer. It was extraordinary, that the strongly dilated vessels were filled with red blood cells. In another part of the same case was found a massive stricture caused by concentrically deposited substances, which were impregnated with collagenous fibers. Regeneration of the vessels frequently happened adjacent totally obstructed ones. Round-cell infiltrations, granulocytes or other indications of an inflammatory synovitis are found only in a few cases. The intracartilaginous enzymatic reactions, which have been much talked of and which were explained as characteristic of the osteoarthrosis cannot be the cause of the degradation of the cartilage, particularly, because of the normal cell count which is to be found in the synovial fluid. We can answer this problem, if we can prove that the substrates of the chondral metabolism themselves exert a direct or indirect influence on the interstitial connective tissue with induction of the powerful proliferation of the same tissue. The changes in the transit zone would be secondary and their effect on the lining cell layer would increase the progression of the arthrotic events.

Paradoxical Adipose Hyperplasia and Cellular Effects After Cryolipolysis: A Case Report.

PubMed

Seaman, Scott A; Tannan, Shruti C; Cao, Yiqi; Peirce, Shayn M; Gampper, Thomas J

2016-01-01

Cryolipolysis is a noninvasive technique for the reduction of subcutaneous adipose tissue by controlled, localized cooling, causing adipocyte apoptosis, reportedly without affecting surrounding tissue. Although cryolipolysis has a low incidence of adverse side effects 33 cases of paradoxical adipose hyperplasia (PAH) have been reported and the precise pathogenesis of PAH is poorly understood. This present case study of PAH aims to characterize the pathological changes in the adipose tissue of PAH on a cellular level by using multiple different assays [hematoxy lin and eosin staining, LIVE/DEAD staining, BODIPY(®) 558/568 C12 (4,4-Difluoro-5-(2-Thienyl)-4-Bora-3a,4a-Diaza-s-Indacene-3-dodecanoic acid) staining]. to identify the underlying mechanism of PAH and reduce the prevalence of PAH in the future. Tissue with PAH had fewer viable cells, significantly decreased quantities of interstitial cells (p = 0.04), and fewer vessels per adipose tissue area when compared to the control tissue. Adipocytes from the PAH tissue were on average slightly smaller than the control adipocytes. Adipocytes of PAH tissue had irregularly contoured edges when compared to the smooth, round edges of the control tissue. These findings from a neutral third party are contrary to prior reports from the inventors of this technique regarding effects of cryolipolysis on both the microvasculature and interstitial cells in adipose tissue. Our use of different assays to compare cryolipolysis-treated PAH tissue with untreated adipose tissue in the same patient showed adipose tissue that developed PAH was hypocellular and hypovascular. Contrary to prior reports from the inventors, cryolipolysis may cause vessel loss, which could lead to ischemia and/or hypoxia that further contributes to adipocyte death. LEVEL OF EVIDENCE 5: Risk. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis.

PubMed

Shahane, Anupama

2013-07-01

The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and inflammatory myopathies. Pulmonary arterial hypertension (PAH) associated with rheumatic diseases carries a particularly grim prognosis with faster progression of disease and poor response to therapy. Though largely associated with systemic sclerosis, it is being increasingly recognized in other rheumatic diseases. An underlying inflammatory component may explain the poor response to therapy in patients with rheumatic diseases and is a rationale for consideration of immunosuppressive therapy in conjunction with vasodilator therapy in treatment for PAH. Further studies identifying pathogenetic pathways and possible targets of therapy, especially the role of immunomodulatory medications, are warranted.

Inhibition effect of small interfering RNA of connective tissue growth factor on the expression of extracellular matrix molecules in cultured human renal proximal tubular cells.

PubMed

Liu, Yuyuan; Li, Weiwei; Liu, Hong; Peng, Youming; Yang, Qiu; Xiao, Li; Liu, Yinghong; Liu, Fuyou

2014-03-01

In this study, we investigated the effect of small interfering RNA (siRNA) of connective tissue growth factor (CTGF) by pRetro-Super (PRS) retrovirus vector on the expression of CTGF and related extracellular matrix molecules in human renal proximal tubular cells (HKCs) induced by high glucose, to provide help for renal tubulointerstitial fibrosis therapy. HKCs were exposed to d-glucose to observe their dose and time effect, while the mannitol as osmotic control. Retrovirus producing CTGF siRNA were constructed from the inverted oligonucleotides and transferred into packaging cell line PT67 with lipofectamine, and the virus supernatant was used to infect HKC. The expression of CTGF, fibronectin (FN) and collagen-type I (col1) were measured by semi-quantitative RT-PCR and Western blot. In response to high glucose, CTGF expression in HKCs was increased in a dose- and time-dependent manner, whereas the increase did not occur in the osmotic control. Introduction of PRS-CTGF-siRNA resulted in the significant reduction of CTGF, FN, col1 mRNA (p < 0.01, respectively) and CTGF, col1 protein (p < 0.05, respectively) expression, while PRS void vector group did not have these effects (p > 0.05). CTGF siRNA therapy can effectively reduce the levels of CTGF, FN and col1 induced by high glucose in cultured HKCs, which suggested that it may be a potential therapeutic strategy to prevent the renal interstitial fibrosis in the future.

An analysis of the clinical features of lung cancer in patients with connective tissue diseases.

PubMed

Saijo, Atsuro; Hanibuchi, Masaki; Goto, Hisatsugu; Toyoda, Yuko; Tezuka, Toshifumi; Nishioka, Yasuhiko

2017-03-01

Patients with connective tissue diseases (CTDs) are at increased risk for lung cancer (LC); interstitial lung disease (ILD) is a common form of organ dysfunction in cases of CTD. However, the influence of ILD on the treatment and prognosis in LC patients with CTD is unclear. Between January 2010 and December 2014, 27 patients among all patients with CTD at our institution were diagnosed with primary LC. We retrospectively analyzed the clinical features, treatment modalities, and outcomes of these patients, and evaluated the potential prognostic factors. Forty-four LC patients without CTD were also analyzed as a control cohort. LC patients with CTD had a significantly higher incidence of ILD as a complication compared with those without CTD (52% and 14%, respectively). CTD-associated ILD (CTD-ILD) at diagnosis was associated with significantly worse survival in LC patients with CTD. Multivariate analysis demonstrated that the complication of CTD-ILD was an independent poor prognostic factor in LC patients with CTD. The incidence of acute exacerbation (AE) of CTD-ILD was 21% among LC patients with CTD, and all of these patients died despite intensive treatment including high-dose corticosteroids. The restrictions in curative therapy for LC due to the presence of ILD and AE of CTD-ILD were thought to be the major reasons for the poor outcome. LC patients with CTD had a high prevalence of ILD, and the presence of CTD-ILD was significantly associated with poor prognosis. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Pulmonary involvement in long-term mixed connective tissue disease: functional trends and image findings after 10 years.

PubMed

Kawano-Dourado, Leticia; Baldi, Bruno G; Kay, Fernando U; Dias, Olivia M; Gripp, Thais E H; Gomes, Paula S; Fuller, Ricardo; Caleiro, Maria T C; Kairalla, Ronaldo A; Carvalho, Carlos R R

2015-01-01

Interstitial lung disease (ILD) is highly prevalent in patients with mixed connective tissue disease (MCTD). However, little is known about the long-term progression of ILD in MCTD. The aims of this study were to describe pulmonary function test (PFT) and high-resolution computed tomography (HRCT) results in long-term MCTD patients, to measure changes in PFT and HRCT results over a 10-year period, and to ascertain correlations in functional and imaging data. In this retrospective cohort study, comparison between baseline and follow-up PFT and HRCT data was performed for 39 unselected consecutive MCTD patients. At baseline, 51% of the patients had abnormal PFTs. Forced vital capacity (FVC) was slightly reduced at baseline (77% of predicted), but remained stable after 10 years. A relative decrease of 15% in the diffusion capacity for carbon monoxide (DLCO) was detected (from 84% to 71% of predicted, p<0.001). The median lower lobes ILD-HRCT score progressed from 7.5% at baseline to 11.2% at follow-up (p=0.02), and findings of traction bronchiolectasis and honeycombing increased (p<0.05). A moderate negative correlation was observed between functional parameters and quantification of image findings. Functional and radiologic alterations suggestive of ILD in long-term MCTD patients are prevalent, mild, and progressed slightly over time. The most sensitive parameters for detecting subtle progression of ILD in MCTD patients are trends in DLCO, quantification of lower-lobes disease by HRCT (lower-lobes %ILD-HRCT score), and qualitative analysis of HRCT imaging.

Pulmonary MR imaging with ultra-short TEs: utility for disease severity assessment of connective tissue disease patients.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; van Cauteren, Marc; Sugimura, Kazuro

2013-08-01

To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2 maps were generated from each MR data set, and mean T2 values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2 values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2 values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Mean T2 values for normal and CTD subjects were significantly different (p=0.0019) and showed significant correlations with %VC, %DLCO, serum KL-6 and CT-based disease severity of CTD patients (p<0.05). Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Oxygen dependence of respiration in rat spinotrapezius muscle in situ

PubMed Central

Pittman, Roland N.

2012-01-01

The oxygen dependence of respiration in striated muscle in situ was studied by measuring the rate of decrease of interstitial Po2 [oxygen disappearance curve (ODC)] following rapid arrest of blood flow by pneumatic tissue compression, which ejected red blood cells from the muscle vessels and made the ODC independent from oxygen bound to hemoglobin. After the contribution of photo-consumption of oxygen by the method was evaluated and accounted for, the corrected ODCs were converted into the Po2 dependence of oxygen consumption, V̇o2, proportional to the rate of Po2 decrease. Fitting equations obtained from a model of heterogeneous intracellular Po2 were applied to recover the parameters describing respiration in muscle fibers, with a predicted sigmoidal shape for the dependence of V̇o2 on Po2. This curve consists of two regions connected by the point for critical Po2 of the cell (i.e., Po2 at the sarcolemma when the center of the cell becomes anoxic). The critical Po2 was below the Po2 for half-maximal respiratory rate (P50) for the cells. In six muscles at rest, the rate of oxygen consumption was 139 ± 6 nl O2/cm3·s and mitochondrial P50 was k = 10.5 ± 0.8 mmHg. The range of Po2 values inside the muscle fibers was found to be 4–5 mmHg at the critical Po2. The oxygen dependence of respiration can be studied in thin muscles under different experimental conditions. In resting muscle, the critical Po2 was substantially lower than the interstitial Po2 of 53 ± 2 mmHg, a finding that indicates that V̇o2 under this circumstance is independent of oxygen supply and is discordant with the conventional hypothesis of metabolic regulation of the oxygen supply to tissue. PMID:22523254

Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle.

PubMed

Nugent, William H; Song, Bjorn K; Pittman, Roland N; Golub, Aleksander S

2016-05-01

Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle. The compression pressure was optimized to 120-130 mmHg without adverse effect on the tissue preparation. A cycle of 5s compression followed by 15s recovery yielded a resting VO2 of 0.98 ± 0.03 ml O2/100 cm(3)min while preserving microvascular oxygen delivery. The measurement system was then used to assess VO2 dependence on PISFO2 at rest and further tested under conditions of isometric muscle contraction to demonstrate a robust ability to monitor the on-kinetics of tissue respiration and the compensatory changes in PISFO2 during contraction and recovery. The temporal and spatial resolution of this approach is well suited to studies seeking to characterize microvascular oxygen supply and demand in thin tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

Tissue dielectric measurement using an interstitial dipole antenna.

PubMed

Wang, Peng; Brace, Christopher L

2012-01-01

The purpose of this study was to develop a technique to measure the dielectric properties of biological tissues with an interstitial dipole antenna based upon previous efforts for open-ended coaxial probes. The primary motivation for this technique is to facilitate treatment monitoring during microwave tumor ablation by utilizing the heating antenna without additional intervention or interruption of the treatment. The complex permittivity of a tissue volume surrounding the antenna was calculated from reflection coefficients measured after high-temperature microwave heating by using a rational function model of the antenna's input admittance. Three referencing liquids were needed for measurement calibration. The dielectric measurement technique was validated ex vivo in normal and ablated bovine livers. Relative permittivity and effective conductivity were lower in the ablation zone when compared to normal tissue, consistent with previous results. The dipole technique demonstrated a mean 10% difference of permittivity values when compared to open-ended coaxial cable measurements in the frequency range of 0.5-20 GHz. Variability in measured permittivities could be smoothed by fitting to a Cole-Cole dispersion model. Further development of this technique may facilitate real-time monitoring of microwave ablation treatments through the treatment applicator. © 2011 IEEE

Tissue Dielectric Measurement Using an Interstitial Dipole Antenna

PubMed Central

Wang, Peng; Brace, Christopher L.

2012-01-01

The purpose of this study was to develop a technique to measure the dielectric properties of biological tissues with an interstitial dipole antenna based upon previous efforts for open-ended coaxial probes. The primary motivation for this technique is to facilitate treatment monitoring during microwave tumor ablation by utilizing the heating antenna without additional intervention or interruption of the treatment. The complex permittivity of a tissue volume surrounding the antenna was calculated from reflection coefficients measured after high-temperature microwave heating by using a rational function model of the antenna’s input admittance. Three referencing liquids were needed for measurement calibration. The dielectric measurement technique was validated ex vivo in normal and ablated bovine livers. Relative permittivity and effective conductivity were lower in the ablation zone when compared to normal tissue, consistent with previous results. The dipole technique demonstrated a mean 10% difference of permittivity values when compared to open-ended coaxial cable measurements in the frequency range of 0.5–20 GHz. Variability in measured permittivities could be smoothed by fitting to a Cole–Cole dispersion model. Further development of this technique may facilitate real-time monitoring of microwave ablation treatments through the treatment applicator. PMID:21914566

Interstitial hyperthermia treatment of countercurrent vascular tissue: a comparison of Pennes, WJ and porous media bioheat models.

PubMed

Hassanpour, Saied; Saboonchi, Ahmad

2014-12-01

Development of appropriate heat transfer models to investigate the thermal behavior of living tissues has become increasingly important in simulations of cancer hyperthermia. In this paper, a review is initially presented of the more important general models developed for heat transfer description of perfused tissues. Comparisons are then made between Pennes' simplified Weinbaum and Jiji "WJ" and the more recent porous media "PM" bioheat models. For this purpose, a mathematical model is developed for the heat transfer in a cylindrical medium containing parallel counter-current pairs of small vessels with characteristics as much as possible similar to those of living tissues. The validity of the models is examined and confirmed using the Pennes in vivo experiments and one-dimensional analytical solutions. For consideration of interstitial hyperthermia treatment the smaller cylindrical zone with typical heat generation, is assumed in the center of the main cylinder. The numerical simulation results revealed that, despite difference in temperature distributions calculated by these three models at normal condition, the heat affected zone at hyperthermic condition predicted by all three models are similar. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integrative models of vascular remodeling during tumor growth

PubMed Central

Rieger, Heiko; Welter, Michael

2015-01-01

Malignant solid tumors recruit the blood vessel network of the host tissue for nutrient supply, continuous growth, and gain of metastatic potential. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature that is in many respects different from the hierarchically organized arterio-venous blood vessel network of the host tissues. Integrative models based on detailed experimental data and physical laws implement in silico the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. In this review, we give an overview over the current status of integrative models describing tumor growth, vascular remodeling, blood and interstitial fluid flow, drug delivery, and concomitant transformations of the microenvironment. © 2015 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. PMID:25808551

Assessment of Parylene C Thin Films for Heart Valve Tissue Engineering

PubMed Central

Marei, Isra; Chester, Adrian; Carubelli, Ivan; Prodromakis, Themistoklis; Trantidou, Tatiana

2015-01-01

Background: Scaffolds are a key component of tissue-engineered heart valves (TEHVs). Several approaches had been adopted in the design of scaffolds using both natural and synthetic resources. We have investigated the suitability of parylene C (PC), a vapor deposited polymeric material, for the use as a scaffold in TEHV. Aims: To evaluate the adsorption of extracellular matrix components onto plasma-activated PC and study the biocompatibility of PC by measuring cellular adhesion, viability, apoptosis, and phenotypic expression of valve endothelial and interstitial cells. Finally, the mechanical properties of PC were compared with those of native aortic valve cusp tissue. Methods: PC slides were plasma activated and then coated with gelatin, type I collagen, or fibronectin. Porcine pulmonary valve endothelial and interstitial cells were then grown on plasma oxidized PC with different types of coatings and their adhesion was observed after 20 h of incubation. Cell viability was tested using the MTS assay, and apoptosis was estimated using TUNEL staining. The mechanical properties of PC and valve tissue were measured using a Bose Mechanical Tester. Finally, cell-seeded PC films were exposed to pulsatile pressure and aortic shear stress, respectively, to test their durability in a dynamic environment. Results: Our findings show that collagen and fibronectin could bind to plasma oxidized PC. Both valve endothelial and interstitial cells adhered to protein-coated ECM. PC had a profile of mechanical stiffness and ultimate tensile strength that were comparable with or in excess of those seen in porcine aortic valve cusps. Cells were still attached to PC films after 3 days of exposure to up to 50 mmHg pulsatile pressure or aortic levels of shear stress. Conclusion: PC is a promising candidate for use as a scaffold in tissue engineering heart valves. Additional studies are required to determine both the durability and long-term performance of cell-seeded PC when in a similar hemodynamic environment to that of the aortic valve. PMID:26101808

Acute interstitial pneumonia (Hamman-Rich syndrome) in idiopathic pulmonary fibrosis and bronchoalveolar carcinoma: a case report.

PubMed

Plasek, Jiri; Dvorackova, Jana; Jahoda, Jan; Trulikova, Kristina; Mokosova, Radka; Danek, Tomas; Hrabovsky, Vladimir; Martinek, Arnost

2011-12-01

Acute interstitial pneumonia is characterized by rapid progressive dyspnoea degenerating into respiratory failure requiring mechanical ventilation. Acute interstitial pneumonia (AIP) and idiopathic pulmonary fibrosis (IPF) are separate clinic/pathological entities although overlap may be present. It is well-known that patients with IPF have increased risk of lung carcinoma; Adenocarcinoma in connection with IPF is less common. Moreover the subtype of adenocarcinoma, diffuse bronchoalveolar carcinoma has not yet been described. We report the case of 45 yr old former hockey player with increased bilateral reticular shadowing on chest radiograph, dyspnoea, velcro-like crackles, restrictive respiratory disease and mixed high-resolution computed tomography finding. During brief in-patient treatment the patient developed acute respiratory failure accompanied by multiorgan failure and disseminated coagulopathy. Deterioration of the microcirculation was followed by loss of peripheral vascular resistance, which was irreversible even with normalization of the blood gases achieved by extracorporeal membrane oxygenation. At autopsy, bronchoalveolar carcinoma in usual interstitial pneumonia (UIP) combined with areas of alveolar damage with hyaline membranes was found. This case alerts clinicians to unusual idiopathic pulmonary fibrosis manifestations and its complications. Close collaboration between clinicians, pathologists and laboratory physicians is highly recommended for early diagnosis and appropriate treatment.

Real-time temperature monitoring with fiber Bragg grating sensor during diffuser-assisted laser-induced interstitial thermotherapy.

PubMed

Pham, Ngot Thi; Lee, Seul Lee; Park, Suhyun; Lee, Yong Wook; Kang, Hyun Wook

2017-04-01

High-sensitivity temperature sensors have been used to validate real-time thermal responses in tissue during photothermal treatment. The objective of the current study was to evaluate the feasible application of a fiber Bragg grating (FBG) sensor for diffuser-assisted laser-induced interstitial thermotherapy (LITT) particularly to treat tubular tissue disease. A 600 - ? m core-diameter diffuser was employed to deliver 980-nm laser light for coagulation treatment. Both a thermocouple and a FBG were comparatively tested to evaluate temperature measurements in ex vivo liver tissue. The degree of tissue denaturation was estimated as a function of irradiation times and quantitatively compared with light distribution as well as temperature development. At the closer distance to a heat source, the thermocouple measured up to 41% higher maximum temperature than the FBG sensor did after 120-s irradiation (i.e., 98.7 ° C ± 6.1 ° C for FBG versus 131.0 ° C ± 5.1 ° C for thermocouple; p < 0.001 ). Ex vivo porcine urethra tests confirmed the real-time temperature measurements of the FBG sensor as well as consistently circumferential tissue denaturation after 72-s irradiation ( coagulation thickness = 2.2 ± 0.3 ?? mm ). The implementation of FBG can be a feasible sensing technique to instantaneously monitor the temperature developments during diffuser-assisted LITT for treatment of tubular tissue structure.

Susceptibility of interstitial continuous glucose monitor performance to sleeping position.

PubMed

Mensh, Brett D; Wisniewski, Natalie A; Neil, Brian M; Burnett, Daniel R

2013-07-01

Developing a round-the-clock artificial pancreas requires accurate and stable continuous glucose monitoring. The most widely used continuous glucose monitors (CGMs) are percutaneous, with the sensor residing in the interstitial space. Inaccuracies in percutaneous CGM readings during periods of lying on the devices (e.g., in various sleeping positions) have been anecdotally reported but not systematically studied. In order to assess the impact of sleep and sleep position on CGM performance, we conducted a study in human subjects in which we measured the variability of interstitial CGM data at night as a function of sleeping position. Commercially available sensors were placed for 4 days in the abdominal subcutaneous tissue in healthy, nondiabetic volunteers (four sensors per person, two per side). Nocturnal sleeping position was determined from video recordings and correlated to sensor data. We observed that, although the median of the four sensor readings was typically 70-110 mg/dl during sleep, individual sensors intermittently exhibited aberrant glucose readings (>25 mg/dl away from median) and that these aberrant readings were strongly correlated with subjects lying on the sensors. We expected and observed that most of these aberrant sleep-position-related CGM readings were sudden decreases in reported glucose values, presumably due to local blood-flow decreases caused by tissue compression. Curiously, in rare cases, the aberrant CGM readings were elevated values. These findings highlight limitations in our understanding of interstitial fluid physiology in the subcutaneous space and have significant implications for the utilization of sensors in the construction of an artificial pancreas. © 2013 Diabetes Technology Society.

Near-infrared fiber delivery systems for interstitial photothermal therapy

NASA Astrophysics Data System (ADS)

Slatkine, Michael; Mead, Douglass S.; Konwitz, Eli; Rosenberg, Zvi

1995-05-01

Interstitial photothermal coagulation has long been recognized as a potential important, minimally invasive modality for treating a variety of pathologic conditions. We present two different technologies for interstitial photothermal coagulation of tissue with infrared lasers: An optical fiber with a radially symmetric diffusing tip for deep coagulation, and a flat bare fiber for the coagulation of thin and long lesions by longitudinally moving the fiber while lasing in concert. Urology and Gynecology Fibers: The fibers are 600 microns diameter with 20 - 40 mm frosted distal tips protected by a smooth transparent cover. When used with a Neodymium:YAG (Nd:YAG) laser, the active fiber surface diffuses optical radiation in a radial pattern, delivering up to 40 W power, and thus providing consistent and uniform interstitial photothermal therapy. Coagulation depth ranges from 4 to 15 mm. Animal studies in the United States and clinical studies in Europe have demonstrated the feasibility of using these fibers to treat benign prostatic hyperplasia and endometrial coagulation. Rhinology Fiber: The fiber is an 800 micron diameter flat fiber operated at 8 W power level while being interstitially pushed and pulled along its axis. A long and thin coagulated zone is produced. The fiber is routinely used for the shrinking of hypertrophic turbinates without surrounding and bone mucusal damage in ambulatory environments.

Comparative physiology of mice and rats: radiometric measurement of vascular parameters in rodent tissues.

PubMed

Boswell, C Andrew; Mundo, Eduardo E; Ulufatu, Sheila; Bumbaca, Daniela; Cahaya, Hendry S; Majidy, Nicholas; Van Hoy, Marjie; Schweiger, Michelle G; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A

2014-05-05

A solid understanding of physiology is beneficial in optimizing drug delivery and in the development of clinically predictive models of drug disposition kinetics. Although an abundance of data exists in the literature, it is often confounded by the use of various experimental methods and a lack of consensus in values from different sources. To help address this deficiency, we sought to directly compare three important vascular parameters at the tissue level using the same experimental approach in both mice and rats. Interstitial volume, vascular volume, and blood flow were radiometrically measured in selected harvested tissues of both species by extracellular marker infusion, red blood cell labeling, and rubidium chloride bolus distribution, respectively. The latter two parameters were further compared by whole-body autoradiographic imaging. An overall good interspecies agreement was observed for interstitial volume and blood flow on a weight-normalized basis in most tissues. In contrast, the measured vascular volumes of most rat tissues were higher than for mouse. Mice and rats, the two most commonly utilized rodent species in translational drug development, should not be considered as interchangeable in terms of vascular volume per gram of tissue. This will be particularly critical in biodistribution studies of drugs, as the amount of drug in the residual blood of tissues is often not negligible, especially for biologic drugs (e.g., antibodies) having long circulation half-lives. Physiologically based models of drug pharmacokinetics and/or pharmacodynamics also rely on accurate knowledge of biological parameters in tissues. For tissue parameters with poor interspecies agreement, the significance and possible drivers are discussed.

Changes in lung ultrastructure following heterologous and homologous serum albumin infusion in the treatment of hemorrhagic shock.

PubMed Central

Moss, G S; Das Gupta, T K; Brinkman, R; Sehgal, L; Newsom, B

1979-01-01

The object of this study was to compare the ultrastructure pulmonary effects of the infusion of homologous and heterologous serum albumin solution in the treatment of hemorrhagic shock in baboons. Adult baboons subjected to hemorrhagic shock were resuscitated with either baboon serum albumin, human serum albumin, or Ringer's lactate solution. The lungs were fixed in vivo with potassium pyroantimony, a solution which produces electron dense interstitial precipitation of sodium. The lungs from animals resuscitated with baboon serum albumin showed evidence of interstitial edema, including dispersion of collagen fibers, interstitial smudging and increased interstital sodium concentrations. Similar changes were seen following human serum albumin infusions. Lung tissue from animals treated with Ringer's lactate solution showed minimal changes from normal. These results suggest that interstitial pulmonary edema develops after either homologous or heterologous serum albumin infusion in the treatment of hemorrhagic shock in baboons. Images Figs. 2a and b. Figs. 3a and b. Figs. 4a and b. Figs. 5a and b. Figs. 6a and b. PMID:106780

Raman microspectroscopy as a diagnostic tool for the non-invasive analysis of fibrillin-1 deficiency in the skin and in the in vitro skin models.

PubMed

Brauchle, Eva; Bauer, Hannah; Fernes, Patrick; Zuk, Alexandra; Schenke-Layland, Katja; Sengle, Gerhard

2017-04-01

Fibrillin microfibrils and elastic fibers are critical determinants of elastic tissues where they define as tissue-specific architectures vital mechanical properties such as pliability and elastic recoil. Fibrillin microfibrils also facilitate elastic fiber formation and support the association of epithelial cells with the interstitial matrix. Mutations in fibrillin-1 (FBN1) are causative for the Marfan syndrome, a congenital multisystem disorder characterized by progressive deterioration of the fibrillin microfibril/ elastic fiber architecture in the cardiovascular, musculoskeletal, ocular, and dermal system. In this study, we utilized Raman microspectroscopy in combination with principal component analysis (PCA) to analyze the molecular consequences of fibrillin-1 deficiency in skin of a mouse model (GT8) of Marfan syndrome. In addition, full-thickness skin models incorporating murine wild-type and Fbn1 GT8/GT8 fibroblasts as well as human HaCaT keratinocytes were generated and analyzed. Skin models containing GT8 fibroblasts showed an altered epidermal morphology when compared to wild-type models indicating a new role for fibrillin-1 in dermal-epidermal crosstalk. Obtained Raman spectra together with PCA allowed to discriminate between healthy and deficient microfibrillar networks in murine dermis and skin models. Interestingly, results obtained from GT8 dermis and skin models showed similar alterations in molecular signatures triggered by fibrillin-1 deficiency such as amide III vibrations and decreased levels of glycan vibrations. Overall, this study indicates that Raman microspectroscopy has the potential to analyze subtle changes in fibrillin-1 microfibrils and elastic fiber networks. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Mutations in building blocks of the fibrillin microfibril/ elastic fiber network manifest in disease conditions such as aneurysms, emphysema or lax skin. Understanding how structural changes induced by fibrillin-1 mutation impact the architecture of fibrillin microfibrils, which then translates into an altered activation state of targeted growth factors, represents a huge challenge in elucidating the genotype-phenotype correlations in connective tissue disorders such as Marfan syndrome. This study shows that Raman microspectroscopy is able to reveal structural changes in fibrillin-1 microfibrils and elastic fiber networks and to discriminate between normal and diseased networks in vivo and in vitro. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mechanics of Fluid-Filled Interstitial Gaps. II. Gap Characteristics in Xenopus Embryonic Ectoderm.

PubMed

Barua, Debanjan; Parent, Serge E; Winklbauer, Rudolf

2017-08-22

The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 μm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m 2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Brain interstitial fluid TNF-α after subarachnoid hemorrhage

PubMed Central

Hanafy, Khalid A.; Grobelny, Bartosz; Fernandez, Luis; Kurtz, Pedro; Connolly, ES; Mayer, Stephan A.; Schindler, Christian; Badjatia, Neeraj

2010-01-01

Objective: TNF-α is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-α may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). Methods: We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8 hours and recorded at the same point that brain interstitial fluid TNF-α was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. Results: Each patient had a mean of 9 brain tissue TNF-α measurements obtained over an average of 72 hours of monitoring. TNF-α levels rose progressively over time. Predictors of elevated brain interstitial TNF-α included higher brain interstitial fluid glucose levels (β=0.066, P<0.02), intraventricular hemorrhage (β=0.085, P<0.021), and aneurysm size >6 mm (β=0.14, p<0.001). There was no relationship between TNF-α levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio. Interpretation: Brain interstitial TNF-α levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels. PMID:20110094

Minimally invasive ultrasound thermal therapy with MR thermal monitoring and guidance

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Stafford, R. Jason; Price, Roger E.; Nau, William H.; Tyreus, Per Daniel; Rivera, Belinda; Schomer, Donald; Olsson, Lars; Hazle, John D.

2001-06-01

In this study both transurethral and interstitial ultrasound thermal therapy were applied to thermally coagulate targeted portions of the canine prostate or brain and implanted TVT tumors while using MRI-based thermal mapping techniques to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. The complex phase-difference mapping technique using an iGE-EPI sequence with lipid suppression was used for determining temperature elevations within the in vivo prostate or brain and surrounding structures. Calculated temperature distributions, thermal dose exposures, T2-wieghted & T1-contrast enhanced images, gross inspection, and histology of sectioned prostates and brains were in good agreement with each other in defining destroyed tissue zones. Interstitial and transurethral ultrasound applicators produce directed zones of thermal coagulation within targeted tissue and implanted tumor, which can be accurately monitored and evaluated by MRI.

Physiology of Fluid and Electrolyte Responses During Inactivity: Water Immersion and Bed Rest

NASA Technical Reports Server (NTRS)

Greenleaf, John E.

1984-01-01

This manuscript emphasizes the physiology of fluid-electrolyte-hormonal responses during the prolonged inactivity of bed rest and water immersion. An understanding of the total mechanism of adaptation (deconditioning) should provide more insight into the conditioning process. Findings that need to be confirmed during bed rest and immersion are: (1) the volume and tissues of origin of fluid shifted to the thorax and head; (2) interstitial fluid pressure changes in muscle and subcutaneous tissue, particularly during immersion; and (3) the composition of the incoming presumably interstitial fluid that contributes to the early hypervolemia. Better resolution of the time course and source of the diuretic fluid is needed. Important data will be forthcoming when hypotheses are tested involving the probable action of the emerging diuretic and natriuretic hormones, between themselves and among vasopressin and aldosterone, on diuresis and blood pressure control.

An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis

PubMed Central

Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon

2011-01-01

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment. PMID:22205850

An adult case of chronic active Epstein-Barr virus infection with interstitial pneumonitis.

PubMed

Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon; Peck, Kyong Ran

2011-12-01

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.

Quantitative dual-probe microdialysis: mathematical model and analysis.

PubMed

Chen, Kevin C; Höistad, Malin; Kehr, Jan; Fuxe, Kjell; Nicholson, Charles

2002-04-01

Steady-state microdialysis is a widely used technique to monitor the concentration changes and distributions of substances in tissues. To obtain more information about brain tissue properties from microdialysis, a dual-probe approach was applied to infuse and sample the radiotracer, [3H]mannitol, simultaneously both in agar gel and in the rat striatum. Because the molecules released by one probe and collected by the other must diffuse through the interstitial space, the concentration profile exhibits dynamic behavior that permits the assessment of the diffusion characteristics in the brain extracellular space and the clearance characteristics. In this paper a mathematical model for dual-probe microdialysis was developed to study brain interstitial diffusion and clearance processes. Theoretical expressions for the spatial distribution of the infused tracer in the brain extracellular space and the temporal concentration at the probe outlet were derived. A fitting program was developed using the simplex algorithm, which finds local minima of the standard deviations between experiments and theory by adjusting the relevant parameters. The theoretical curves accurately fitted the experimental data and generated realistic diffusion parameters, implying that the mathematical model is capable of predicting the interstitial diffusion behavior of [3H]mannitol and that it will be a valuable quantitative tool in dual-probe microdialysis.

Image guidance, treatment planning and evaluation of cancer interstitial focal therapy using liposomal radionuclides

NASA Astrophysics Data System (ADS)

Ware, Steve William

Focally ablative therapy of cancer has gained significant interest recently. Improvements in diagnostic techniques have created possibilities for treatment which were once clinically unfeasible. Imaging must be capable of allowing accurate diagnosis, staging and planning upon initiation of therapy. Recent improvements in MRI and molecular imaging techniques have made it possible to accurately localize lesions and in so doing, improve the accuracy of proposed focal treatments. Using multimodality imaging it is now possible to target, plan and evaluate interstitial focal treatment using liposome encapsulated beta emitting radionuclides in a variety of cancer types. Since most absorbed dose is deposited early and heterogeneously in beta-radionuclide therapy, investigation of the resultant molecular and cellular events during this time is important for evaluating treatment efficacy. Additionally, investigating a multifocal entity such as prostate cancer is helpful for determining whether MRI is capable of discriminating the proper lesion for therapy. Correlation of MRI findings with histopathology can further improve the accuracy of interstitial focal radionuclide therapy by providing non-invasive surrogates for tissue compartment sizes. In the application of such therapies, compartmental sizes are known to heavily influence the distribution of injected agents. This has clear dosimetric implications with the potential to significantly alter the efficacy of treatment. The hypothesis of this project was that multimodality imaging with magnetic resonance imaging (MRI), autoradiography (AR), and single photon emission computed tomography (SPECT) could be used to target, plan, and evaluate interstitial focal therapy with non-sealed source, liposome-encapsulated 186Re beta emitting radionuclides. The specific aims of this project were to 1) Identify suitable targets for interstitial focal therapy. This was done by retrospectively analyzing MRI data to characterize the tumor microenvironment through correlation with in-plane compartmental sizes obtained from histopathology analysis of step-sectioned prostatectomy specimens; 2) Gauge the ability of a reader to plan an interstitial focal treatment using MRI. This was accomplished by objective measures of contrast and volume measurement with subjective reader analysis of tumor conspicuities; 3) Evaluation of the early biologic response to 186Re interstitial focal therapy. This was achieved by correlation of histochemistry (HC) markers: hetrochromatin protein alpha (HP1α), cluster of differentiation 34 (CD34), terminal deoxynucleotidal transferase nick end labeling (TUNEL), caspase 3, Ki-67 and hematoxylin & eosin (H&E) to the radiation distribution as seen on AR and radiation absorbed dose as computed from planar imaging. The conclusions of this study are that prostate MRI allows targeting of appropriate lesions for therapy by its ability to inform on the tumor microenvironment. MRI distinguishes prostatic tumors on the basis of tissue composition. Readers are better able reproduce volumes and thus plan interstitial therapy for tumors which have a denser, more homogeneous composition. The combination of SPECT and autoradiography showed a dose and position dependent expression of HC markers. These results demonstrate that multimodality imaging is capable of targeting, planning and evaluating interstitial focal therapy.

Nanoscale Viscoelasticity of Extracellular Matrix Proteins in Soft Tissues: a Multiscale Approach

PubMed Central

Miri, Amir K.; Heris, Hossein K.; Mongeau, Luc; Javid, Farhad

2013-01-01

We propose that the bulk viscoelasticity of soft tissues results from two length-scale-dependent mechanisms: the time-dependent response of extracellular matrix proteins (ECM) at the nanometer scale and the biophysical interactions between the ECM solid structure and interstitial fluid at the micrometer scale. The latter was modeled using the poroelasticity theory with an assumption of free motion of the interstitial fluid within the porous ECM structure. Following a recent study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013. Journal of the Mechanical Behavior of Biomedical Materials), atomic force microscopy was used to perform creep loading and 50-nm sinusoidal oscillations on porcine vocal folds. The proposed model was calibrated by a finite element model to accurately predict the nanoscale viscoelastic moduli of ECM. A linear correlation was observed between the in-depth distribution of the viscoelastic moduli and that of hyaluronic acids in the vocal fold tissue. We conclude that hyaluronic acids may regulate the vocal fold viscoelasticity at nanoscale. The proposed methodology offers a characterization tool for biomaterials used in vocal fold augmentations. PMID:24317493

Fluid shifts and muscle function in humans during acute simulated weightlessness

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Tipton, C. M.; Gollnick, P. D.; Mubarak, S. J.; Tucker, B. J.; Akeson, W. H.

1983-01-01

The acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surface reflex time were studied in eight supine human subjects who were placed in a 5 degrees head-down tilt position for 8 hr. Results show a cephalic fluid shift from the legs as indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. The interstitial fluid pressure in the tibialis anterior muscle and subcutaneous tissue of the lower leg was found to fall significantly, while other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. The total water content of the soleus muscle was unchanged during the head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged, while the triceps surae reflex time associated with plantar flexion movement slowed slightly. These results demonstrate a dehydration effect of head-down tilt on muscle and subcutaneous tissue of the lower leg that may affect muscle function.

Acute interstitial pneumonia in feedlot cattle: effects of feeding feather meal or vitamin E

PubMed Central

Stanford, Kim; McAllister, Tim A.; Ayroud, Mejid; Bray, Tammy M.; Yost, Garold S.

2007-01-01

We evaluated the effects of feeding 1.5% cysteine-rich feather meal or 550 IU of vitamin E for 40 d before slaughter on the rates of death and emergency slaughter due to acute interstitial pneumonia (AIP) in commercial feedlots. Blood and lung tissue were collected at slaughter from 83 animals clinically diagnosed with AIP, 40 asymptomatic penmates, and 40 heifers receiving either feather meal (20) or vitamin E (20); the left lung was subsampled for histologic examination. Blood and lung tissue were analyzed for thiol adducts of 3-methyleneindolenine (3ME) and reduced glutathione. Supplementation with feather meal or vitamin E had no effect on the rates of death and emergency slaughter attributable to AIP and did not influence the levels of 3ME or reduced glutathione in blood or lung tissue. Although supplementation with greater amounts of feather meal or vitamin E may have been necessary to significantly affect factors related to feedlot AIP, increased supplementation would be uneconomical for commercial feedlots, given the relatively low incidence of AIP. PMID:17479779

Hematopoietic stem cell origin of connective tissues.

PubMed

Ogawa, Makio; Larue, Amanda C; Watson, Patricia M; Watson, Dennis K

2010-07-01

Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications. Copyright 2010 ISEH - Society for Hematology and Stem Cells. All rights reserved.

Characteristics of 106 spontaneous mammary tumours appearing in Sprague-Dawley female rats.

PubMed Central

Okada, M.; Takeuchi, J.; Sobue, M.; Kataoka, K.; Inagaki, Y.; Shigemura, M.; Chiba, T.

1981-01-01

Pathological studies were undertaken on 106 mammary tumours (89 benign, 17 malignant) appearing spontaneously in 95 normal female Sprague-Dawley rats which were killed at Day 756. The benign tumours comprised those with a predominant acinar hyperplasia and those with adenomatous or fibroadenomatous pattern. No significant differences were found histochemically between the acinar cells of the benign tumours and of the lactating gland, except that the amount of fibrous interstitial connective tissue was larger in the former. 3H- or 35S-glycosaminoglycan synthesis by the benign tumours was found to be much higher. The prolactin value in the plasma of the benign-tumour-bearing rats was about 27 times that of 6-month-old virgin rats, and similar to that of rats on the 7th day post partum. Carcinomatous proliferation of tubuloacinar cells could be seen in 5 of the 89 benign tumours. The incidence of benign tumours increases with the age of the rats. Images Fig. 1 Fig. 2 Fig. 3 PMID:7248153

Pleural and pulmonary involvement in systemic lupus erythematosus.

PubMed

Torre, Olga; Harari, Sergio

2011-01-01

Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a multisystem involvement. The clinical manifestations of this disease include an erythematous rash, oral ulcers, polyarthralgia, nonerosive arthritis, polyserositis, hematologic, renal, neurologic, pulmonary and cardiac abnormalties. The involvement of the respiratory system is frequent. Pleuro-pulmonary manifestations are present in almost half of the patients during the disease course and may be the presenting symptoms in 4-5% of patients with SLE. Complications directly associated to the disease include pleuritis with or without pleural effusion, alveolitis, interstitial lung disease, lupus pneumonitis, pulmonary hemorrhage, pulmonary arterial hypertension, and pulmonary thromboembolic disease. Complications due to secondary causes include pleuro-pulmonary manifestations of cardiac and renal failure, atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, and drug toxicity. The prevalence, clinical presentation, prognosis and response to treatment vary, depending on the pattern of involvement. As with other connective tissue diseases, early and specific therapeutic intervention may be indicated for many of these pleuro-pulmonary manifestations. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

PubMed

Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

2014-01-01

To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

Doxorubicin-loaded Zein in situ gel for interstitial chemotherapy.

PubMed

Cao, Xiaoying; Geng, Jianning; Su, Suwen; Zhang, Linan; Xu, Qian; Zhang, Li; Xie, Yinghua; Wu, Shaomei; Sun, Yongjun; Gao, Zibin

2012-01-01

A novel drug delivery system of doxorubicin (DOX)-loaded Zein in situ gel for interstitial chemotherapy was investigated in this study. The possible mechanisms of drug release were described according to morphological analysis by optical microscopy and scanning electronic microscope (SEM). In vitro and in vivo anti-tumor activity studies showed that DOX-loaded Zein in situ gel was superior to DOX solution. Local pharmacokinetics in tumor tissue was studied by quantitative analysis with confocal laser scanning microscopy (CLSM) combined with microdialysis technology. A pharmacokinetics mathematical model of DOX-loaded Zein in situ gel in tumors was then built.

Effects of non-leukocyte-reduced and leukocyte-reduced packed red blood cell transfusions on oxygenation of rat spinotrapezius muscle

PubMed Central

Sundararajan, Sripriya; Dodhy, Sami C.; Pittman, Roland N.; Lewis, Stephen J.

2015-01-01

Leukoreduction of blood used for transfusion alleviates febrile transfusion reactions, graft versus host disease and alloimmunization to leukocyte antigen. However, the actual clinical benefit of leukoreduction in terms of microcirculatory tissue O2 delivery after packed red blood cell (pRBC) transfusion has not been investigated. As such, the aim of this study was to determine the effects of non-leukoreduced (NLR) and leukoreduced (LR) fresh pRBC transfusion on interstitial oxygenation in anesthetized male Sprague-Dawley rats. Interstitial fluid PO2 and arteriolar diameters in spinotrapezius muscle preparations were monitored before and after transfusion with NLR- or LR-pRBCs. The major findings were that (1) transfusion of NLR-pRBCs significantly decreased interstitial oxygenation whereas transfusion of LR-pRBCs did not, and (2) transfusion with LR-pRBCs elicited a substantially greater increase in arterial blood pressure (ABP) than did transfusion with NLR-pRBCs. These changes in PO2 and ABP were not associated with changes in the diameters of resistance arterioles in the spinotrapezius muscle. These data suggest that transfusion of fresh NLR-pRBCs may negatively affect tissue oxygenation via enhanced leukocyte influx and decreased O2 delivery. They also suggest that leukocytes diminish the capability of transfused pRBCs to increase cardiac output. As such, transfusion of LR-pRBCs may be less deleterious on tissue PO2 levels than NLR-pRBCs although a concomitantly greater increase in ABP may accompany transfusion of LR-pRBCs. PMID:24189119

Phosphorescence quenching microrespirometry of skeletal muscle in situ

PubMed Central

Golub, Aleksander S.; Tevald, Michael A.

2011-01-01

We have developed an optical method for the evaluation of the oxygen consumption (V̇o2) in microscopic volumes of spinotrapezius muscle. Using phosphorescence quenching microscopy (PQM) for the measurement of interstitial Po2, together with rapid pneumatic compression of the organ, we recorded the oxygen disappearance curve (ODC) in the muscle of the anesthetized rats. A 0.6-mm diameter area in the tissue, preloaded with the phosphorescent oxygen probe, was excited once a second by a 532-nm Q-switched laser with pulse duration of 15 ns. Each of the evoked phosphorescence decays was analyzed to obtain a sequence of Po2 values that constituted the ODC. Following flow arrest and tissue compression, the interstitial Po2 decreased rapidly and the initial slope of the ODC was used to calculate the V̇o2. Special analysis of instrumental factors affecting the ODC was performed, and the resulting model was used for evaluation of V̇o2. The calculation was based on the observation of only a small amount of residual blood in the tissue after compression. The contribution of oxygen photoconsumption by PQM and oxygen inflow from external sources was evaluated in specially designed tests. The average oxygen consumption of the rat spinotrapezius muscle was V̇o2 = 123.4 ± 13.4 (SE) nl O2/cm3·s (N = 38, within 6 muscles) at a baseline interstitial Po2 of 50.8 ± 2.9 mmHg. This technique has opened the opportunity for monitoring respiration rates in microscopic volumes of functioning skeletal muscle. PMID:20971766

Effect of Strain Field on Threshold Displacement Energy of Tungsten Studied by Molecular Dynamics Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Dong; Gao, Ning; Setyawan, W.

The influence of strain field on defect formation energy and threshold displacement energy (Ed) in body-centered cubic (BCC) tungsten (W) has been studied with molecular dynamics simulations. Two different W potentials (Fikar and Juslin) were compared and the results indicate that the connection distance and selected function linking the short-range and long-range portions of the potentials affects the threshold displacement energy and its direction-specific values. The minimum Ed direction calculated with the Fikar-potential is <100> and with the Juslin-potential is <111>. Nevertheless, the most stable self-interstitial configuration is found to be a <111>-crowdion for both potentials. This stable configuration doesmore » not change with applied strain. Varying the strain from compression to tension increases the vacancy formation energy but decreases the self-interstitial formation energy. The formation energy of a self-interstitial changes more significantly than a vacancy such that Ed decreases with applied hydrostatic strain from compression to tension.« less

Estimating Plasma Glucose from Interstitial Glucose: The Issue of Calibration Algorithms in Commercial Continuous Glucose Monitoring Devices

PubMed Central

Rossetti, Paolo; Bondia, Jorge; Vehí, Josep; Fanelli, Carmine G.

2010-01-01

Evaluation of metabolic control of diabetic people has been classically performed measuring glucose concentrations in blood samples. Due to the potential improvement it offers in diabetes care, continuous glucose monitoring (CGM) in the subcutaneous tissue is gaining popularity among both patients and physicians. However, devices for CGM measure glucose concentration in compartments other than blood, usually the interstitial space. This means that CGM need calibration against blood glucose values, and the accuracy of the estimation of blood glucose will also depend on the calibration algorithm. The complexity of the relationship between glucose dynamics in blood and the interstitial space, contrasts with the simplistic approach of calibration algorithms currently implemented in commercial CGM devices, translating in suboptimal accuracy. The present review will analyze the issue of calibration algorithms for CGM, focusing exclusively on the commercially available glucose sensors. PMID:22163505

Characterization of the Chicken Ovarian Cancer Model

DTIC Science & Technology

2004-08-01

epithelium and usually contain eosinophilic proteinaceous fluid in their lumen. They have variable amounts of interstitial fibrovascular tissue and/or...alterations in oviductal glandular epithelium from normal to neoplastic (focal or multifocal hyperplasia -4 dysplasia -- adenoma [usually polypoid] -4

Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

PubMed Central

Henegar, Corneliu; Tordjman, Joan; Achard, Vincent; Lacasa, Danièle; Cremer, Isabelle; Guerre-Millo, Michèle; Poitou, Christine; Basdevant, Arnaud; Stich, Vladimir; Viguerie, Nathalie; Langin, Dominique; Bedossa, Pierre; Zucker, Jean-Daniel; Clement, Karine

2008-01-01

Background Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be involved in activating inflammatory processes and altering cell composition in white adipose tissue (WAT). However, the overall importance of these alterations, and their long-term impact on the metabolic functions of the WAT and on its morphology, remain unclear. Results Here, we analyzed the transcriptomic signature of the subcutaneous WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomics approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes in order to construct a comprehensive map of transcriptional interactions defining the obese WAT. These analyses highlighted a significant up-regulation of genes and biological themes related to extracellular matrix (ECM) constituents, including members of the integrin family, and suggested that these elements could play a major mediating role in a chain of interactions that connect local inflammatory phenomena to the alteration of WAT metabolic functions in obese subjects. Tissue and cellular investigations, driven by the analysis of transcriptional interactions, revealed an increased amount of interstitial fibrosis in obese WAT, associated with an infiltration of different types of inflammatory cells, and suggest that phenotypic alterations of human pre-adipocytes, induced by a pro-inflammatory environment, may lead to an excessive synthesis of ECM components. Conclusion This study opens new perspectives in understanding the biology of human WAT and its pathologic changes indicative of tissue deterioration associated with the development of obesity. PMID:18208606

Irisin: a potentially candidate marker for myocardial infarction.

PubMed

Kuloglu, Tuncay; Aydin, Suna; Eren, Mehmet Nesimi; Yilmaz, Musa; Sahin, Ibrahim; Kalayci, Mehmet; Sarman, Emine; Kaya, Nalan; Yilmaz, Osman Fatih; Turk, Ahmet; Aydin, Yalcin; Yalcin, Mehmet Hanifi; Uras, Nimet; Gurel, Ali; Ilhan, Selcuk; Gul, Evrim; Aydin, Suleyman

2014-05-01

Myocardial infarction (MI) causes energy depletion through imbalance between coronary blood supply and myocardial demand. Irisin produced by the heart reduces ATP production by increasing heat generation. Energy depletion affects irisin concentration in circulation and cardiac tissues, suggesting an association with MI. We examined: (1) irisin expression immunohistochemically in rat heart, skeletal muscle, kidney and liver in isoproterenol (ISO)-induced MI, and (2) serum irisin concentration by ELISA. Rats were randomly allocated into 6 groups (n=6), (i) control, (ii) ISO (1h), (iii) ISO (2h), (iv) ISO (4h), (v) ISO (6h), and (vi) ISO (24h), 200mg ISO in each case. Rats were decapitated and the blood and tissues collected for irisin analysis. Blood was centrifuged at 1792 g for 5 min. Tissues were washed with saline and fixed in 10% formalin for histology. Serum irisin levels gradually decreased from 1h to 24h in MI rats compared with controls, the minimum being at 2h, increasing again after 6h. Cardiac muscle cells, glomerular, peritubular renal cortical interstitial cells, hepatocytes and liver sinusoidal cells and perimysium, endomysium and nucleoi of skeletal muscle were irisin positive, but its synthesis decreased 1-4h after MI. At all time-points, irisin increased near myocardial connective tissue, with production in skeletal muscle, liver and kidney recovering after 6h, although slower than controls. Unique insight into the pathogenesis of MI is shown, and the gradually decrease of serum irisin might be a diagnostic marker for MI. Copyright © 2014 Elsevier Inc. All rights reserved.

[Effect of a modified low protein and low fat diet on histologic changes and metabolism in kidneys in an experimental model of polycystic kidney disease].

PubMed

Banković-Calić, Neda; Ogbori, Malkom R; Nicman, Evin

2002-01-01

Dietary protein restriction slows progression in numerous animal models of renal diseases. Flax seed has also demonstrated useful anti-inflammatory properties in a number of animal models and human diseases. We undertook several studies to determine if feeding with low protein casein, soy diet and flax seed diet would ameliorate renal injury in Han:SPRD-cy rat model of polycystic kidney disease. Male offspring of Han:SPRD-cy heterozygotes received protein modified diet: ad libidum LP 8% casein in test or 20% casein in control group for 8 weeks; 20% heat treated soy protein or 20% casein in control group two separate studies for 8 weeks ad libidum and pair feeding in 6 weeks; and 10% flax seed diet or control rat chow for 8 weeks from weaning. Tissue was harvested for histological assessment and metabolic changes in lipids, citric acid metabolites and osmolytes. Morphometrically after histochemical and immunohistochemical staining cystic changes, renal tubular proliferation and apoptosis, number of interstitial cells/macrophages infiltration and interstitial fibrosis were measured. Gas chromatography was used for lipid analysis in renal and liver tissue. 1-HNMR spectroscopy was used for urine and tissue organic anion and osmolytes content analysis. RESULTS IN PROTEIN MODIFIED DIET: Casein low protein as well as soy protein fed animals demonstrated reduced PKD pathology: significant reduction in cystic changes, interstitial inflammation and fibrosis and also reduction in tubular cells proliferation and apoptosis. Pair feeding protocol in second soy diet study confirmed that significant effect on renal histology was not because of protein deprivation and growth retardation. 1-H NMR spectroscopy revealed that progression of chronic renal failure in Han:SPRD-cy rat PKD is associated with renal depletion of citric acid cycle metabolite and betaine. Amelioration of PKD by soy protein diet is associated with renal retention of citric acid cycle anions, despite increased excretion and preservation of betaine in renal tissue. Soy feeding increased both hepatic and renal content of linoleic acid and increased renal alpha linolenic acid content, while decreased arachidonic hepatic content. RESULTS IN FLAX SEED SUPPLEMENTATION IN DIET: Flax seed fed animals had moderate decrease in cystic size and less interstitial inflammation and fibrosis while there were no differences in epithelial cell apoptosis and proliferation. Lipid analysis revealed significant renal enrichment of 18 and 20 carbon omega 3 polyunsaturated fatty acids. In flax fed animals there was an increased urinary citrate excretion without significant changes in urinary ammonia excretion, so increased citrate excretion was not due to alkaline effect of the diet. Kidney tissue 1H NMR spectroscopy revealed that disease amelioration was associated with tissue retention of succinate and betaine. Effect on histology: Low casein and soy feeding ameliorates Han: SPRD-cy rat polycystic kidney disease reducing both tubular remodeling and interstitial inflammation and fibrosis, while flax seed diet effect appears to be through moderation of associated interstitial nephritis. Metabolic effect: Soy diet alters the renal content of polyunsaturated fatty acids and enriched renal betaine content with retention of citric acid cycle metabolites despite increased excretion. Flax seed diet alters renal content of polyunsaturated fatty acids and promotes the formation of less inflammatory classes of renal prostanoides. Flax seed diet also enriched renal content of betaine and succinate. Amelioration of Hans:SPRD-cy rat polycystic kidney disease by diet is associated with alteration in the handling of citric acid cycle metabolites and betaine, and also in content of polyunsaturated fatty acids in kidneys and liver. Metabolic pathways in dietary modified renal pathology have to be established.

Cerebral interstitial tissue oxygen tension, pH, HCO3, CO2.

PubMed

Charbel, F T; Hoffman, W E; Misra, M; Hannigan, K; Ausman, J I

1997-10-01

There are many techniques for monitoring the injured brain following trauma, subarachnoid hemorrhage, or surgery. It is thought that the major determinants for recovery of injured cerebral tissue are oxygen, glucose delivery, and the clearance of metabolites. These factors, at optimal levels, are probably responsible for the regaining of neuronal functions. These parameters are in turn dependent on the tissue's blood flow and metabolism. We have been using a single, compact, polyethylene sensor, the Paratrend 7 for the measurement of cerebral oxygen tension, CO2, pH, and temperature. This sensor is designed for continuous blood gas analysis to aid in monitoring neurosurgical patients, both during surgery and in the intensive care unit. Using the Paratrend 7 sensor, we found the normal range of values to be: PO2 33 +/- 11 mm Hg; PCO2 48 +/- 7 mm Hg; pH 7.19 +/- 0.11. Critical measurements are considered to be tissue PO2 < 10 mm Hg; PCO2 > 60 mm Hg, and pH < 6.8. We have had no complications with this device; the risks are similar to those of placing a parenchymal intracranial pressure monitor. We believe that assessment of interstitial cerebral oxygen saturation can be of great value both intraoperatively and postoperatively. In our experience, the Paratrend 7 system is an effective method of measuring tissue cerebral oxygen tension, along with carbon dioxide levels, pH, and temperature.

Cytoskeletal remodeling of connective tissue fibroblasts in response to static stretch is dependent on matrix material properties

PubMed Central

Abbott, Rosalyn D; Koptiuch, Cathryn; Iatridis, James C; Howe, Alan K; Badger, Gary J; Langevin, Helene M

2012-01-01

In areolar “loose” connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in and dissociated from areolar and dense connective tissue in response to 2 hours of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large “sheet-like” morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells’ tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues. PMID:22552950

Mixed Connective Tissue Disease

MedlinePlus

Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...

A multiphysics 3D model of tissue growth under interstitial perfusion in a tissue-engineering bioreactor.

PubMed

Nava, Michele M; Raimondi, Manuela T; Pietrabissa, Riccardo

2013-11-01

The main challenge in engineered cartilage consists in understanding and controlling the growth process towards a functional tissue. Mathematical and computational modelling can help in the optimal design of the bioreactor configuration and in a quantitative understanding of important culture parameters. In this work, we present a multiphysics computational model for the prediction of cartilage tissue growth in an interstitial perfusion bioreactor. The model consists of two separate sub-models, one two-dimensional (2D) sub-model and one three-dimensional (3D) sub-model, which are coupled between each other. These sub-models account both for the hydrodynamic microenvironment imposed by the bioreactor, using a model based on the Navier-Stokes equation, the mass transport equation and the biomass growth. The biomass, assumed as a phase comprising cells and the synthesised extracellular matrix, has been modelled by using a moving boundary approach. In particular, the boundary at the fluid-biomass interface is moving with a velocity depending from the local oxygen concentration and viscous stress. In this work, we show that all parameters predicted, such as oxygen concentration and wall shear stress, by the 2D sub-model with respect to the ones predicted by the 3D sub-model are systematically overestimated and thus the tissue growth, which directly depends on these parameters. This implies that further predictive models for tissue growth should take into account of the three dimensionality of the problem for any scaffold microarchitecture.

Significance of Myositis Autoantibody in Patients with Idiopathic Interstitial Lung Disease

PubMed Central

Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo

2015-01-01

Purpose Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. Materials and Methods A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We analyzed a panel of 11 myositis autoantibody specificities in the patients using a line blot immunoassay. Then, we divided them into myositis autoantibody-positive and -negative groups and compared the clinical features and laboratory data between the two groups. Results Of the 32 idiopathic ILD patients, 12 patients had myositis autoantibodies encompassing 9 specificities, except for anti-Mi-2 and anti-PM-Scl 100 (12/32, 38%). Anti-synthetase autoantibodies including Jo-1, EJ, OJ, PL-7, and PL-12 were present in 7 patients (7/32, 22%). The group with myositis autoantibodies presented more frequently with the symptom of mechanic's hand and showed abnormal pulmonary function test results with low forced vital capacity, diffusing capacity for carbon monoxide, total lung capacity, and high lactate dehydrogenase values in blood when compared with the group without myositis antibodies. Conclusion We strongly suggest that patients undergo an evaluation of myositis autoantibodies, if they are diagnosed with idiopathic ILD in the presence of clinical characteristics including mechanic's hand, arthralgia, and autoantibodies which are insufficient to make a diagnosis of a specific CTD category. PMID:25837172

The Clinical Features of Myositis-Associated Autoantibodies: a Review.

PubMed

Gunawardena, Harsha

2017-02-01

The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases traditionally defined by clinical manifestations including skeletal muscle weakness, skin rashes, elevated skeletal muscle enzymes, and neurophysiological and/or histological evidence of muscle inflammation. Patients with myositis overlap can develop other features including parenchymal lung disease, inflammatory arthritis, gastrointestinal manifestations and marked constitutional symptoms. Although patients may be diagnosed as having polymyositis (PM) or dermatomyositis (DM) under the IIM spectrum, it is quite clear that disease course between subgroups of patients is different. For example, interstitial lung disease may predominate in some, whereas cutaneous complications, cancer risk, or severe refractory myopathy may be a significant feature in others. Therefore, tools that facilitate diagnosis and indicate which patients require more detailed investigation for disease complications are invaluable in clinical practice. The expanding field of autoantibodies (autoAbs) associated with connective tissue disease (CTD)-myositis overlap has generated considerable interest over the last few years. Using an immunological diagnostic approach, this group of heterogeneous conditions can be separated into a number of distinct clinical phenotypes. Rather than diagnose a patient as simply having PM, DM or overlap CTD, we can define syndromes to differentiate disease subsets that emphasise clinical outcomes and guide management. There are now over 15 CTD-myositis overlap autoAbs found in patients with a range of clinical manifestations including interstitial pneumonia, cutaneous disease, cancer-associated myositis and autoimmune-mediated necrotising myopathy. This review describes their diagnostic utility, potential role in disease monitoring and response to treatment. In the future, routine use of these autoAb will allow a stratified approach to managing this complex set of conditions.

Characterization of the liver tissue interstitial fluid (TIF) proteome indicates potential for application in liver disease biomarker discovery.

PubMed

Sun, Wei; Ma, Jie; Wu, Songfeng; Yang, Dong; Yan, Yujuan; Liu, Kehui; Wang, Jinglan; Sun, Longqin; Chen, Ning; Wei, Handong; Zhu, Yunping; Xing, Baocai; Zhao, Xiaohang; Qian, Xiaohong; Jiang, Ying; He, Fuchu

2010-02-05

Tissue interstitial fluid (TIF) forms the interface between circulating body fluids and intracellular fluid. Pathological alterations of liver cells could be reflected in TIF, making it a promising source of liver disease biomarkers. Mouse liver TIF was extracted, separated by SDS-PAGE, analyzed by linear ion trap mass spectrometer, and 1450 proteins were identified. These proteins may be secreted, shed from membrane vesicles, or represent cellular breakdown products. They show different profiling patterns, quantities, and possibly modification/cleavage of intracellular proteins. The high solubility and even distribution of liver TIF supports its suitability for proteome analysis. Comparison of mouse liver TIF data with liver tissue and plasma proteome data identified major proteins that might be released from liver to plasma and serve as blood biomarkers of liver origin. This result was partially supported by comparison of human liver TIF data with human liver and plasma proteome data. Paired TIFs from tumor and nontumor liver tissues of a hepatocellular carcinoma patient were analyzed and the profile of subtracted differential proteins supports the potential for biomarker discovery in TIF. This study is the first analysis of the liver TIF proteome and provides a foundation for further application of TIF in liver disease biomarker discovery.

Effects of hydration on steric and electric charge-induced interstitial volume exclusion--a model.

PubMed

Øien, Alf H; Justad, Sigrid R; Tenstad, Olav; Wiig, Helge

2013-09-03

The presence of collagen and charged macromolecules like glycosaminoglycans (GAGs) in the interstitial space limits the space available for plasma proteins and other macromolecules. This phenomenon, known as interstitial exclusion, is of importance for interstitial fluid volume regulation. Physical/mathematical models are presented for calculating the exclusion of electrically charged and neutral macromolecules that equilibrate in the interstitium under various degrees of hydration. Here, a central hypothesis is that the swelling of highly electrically charged GAGs with increased hydration shields parts of the neutral collagen of the interstitial matrix from interacting with electrically charged macromolecules, such that exclusion of charged macromolecules exhibits change due to steric and charge effects. GAGs are also thought to allow relatively small neutral, but also charged macromolecules neutralized by a very high ionic strength, diffuse into the interior of GAGs, whereas larger macromolecules may not. Thus, in the model, relatively small electrically charged macromolecules, such as human serum albumin, and larger neutral macromolecules such as IgG, will have quite similar total volume exclusion properties in the interstitium. Our results are in agreement with ex vivo and in vivo experiments, and suggest that the charge of GAGs or macromolecular drugs may be targeted to increase the tissue uptake of macromolecular therapeutic agents. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Hemodynamic heterogeneity of connective tissue disease patients with borderline mean pulmonary artery pressure and its distinctive characters from those with normal pulmonary artery pressure: a retrospective study.

PubMed

Asari, Yusa; Yamasaki, Yoshioki; Tsuchida, Kosei; Suzuki, Kengo; Akashi, Yoshihiro J; Okazaki, Takahiro; Ozaki, Shoichi; Yamada, Hidehiro; Kawahata, Kimito

2018-05-18

To clarify whether patients with connective tissue disease (CTD)-associated borderline mean pulmonary artery pressure (mPAP) have distinctive hemodynamic characteristics from those with normal mPAP and whether pathogenesis is as heterogeneous as manifest pulmonary hypertension (PH). Seventy-five CTD patients who underwent right heart catheterization (RHC) from 2008 through 2016 were retrospectively analyzed. We compared between-group differences in clinical and hemodynamic findings: normal mPAP (n = 35), borderline mPAP (n = 15), and PH (n = 25). A therapeutic intervention trial based on RHC results was performed in nine patients. The values of tricuspid regurgitation pressure gradient (TRPG) in patients with borderline mPAP were comparable at rest but became higher after exercise compared to those with a normal mPAP (P = 0.01). Pulmonary artery wedge pressure in patients with borderline mPAP was higher than in those with normal mPAP (P < 0.0001) and comparable to those with PH. Each of the three patients was treated for pre-capillary and post-capillary disease and two for interstitial lung disease (ILD). During the mean follow-up period of 40 months, mPAP or TRPG normalized in all patients treated for pre-capillary and post-capillary disease. One patient with severe ILD developed to PH and died from it. CTD patients with borderline mPAP, the underlining pathogenesis of which is heterogeneous as PH, have distinctive hemodynamic characteristics from those with normal mPAP. Whether a specific treatment targeting the inflammatory process or local hemodynamics may alter the clinical course to PH is a topic for future research.

Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study.

PubMed

Escolà-Vergé, Laura; Pinal-Fernandez, Iago; Fernandez-Codina, Andreu; Callejas-Moraga, Eduardo L; Espinosa, Juan; Marin, Ana; Labrador-Horrillo, Moises; Selva-O'Callaghan, Albert

2017-04-01

Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading. All anti-U1-RNP-positive patients (2010-2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred. Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred. Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.

Vascular Endothelial Cell-Specific Connective Tissue Growth Factor (CTGF) Is Necessary for Development of Chronic Hypoxia-Induced Pulmonary Hypertension.

PubMed

Pi, Liya; Fu, Chunhua; Lu, Yuanquing; Zhou, Junmei; Jorgensen, Marda; Shenoy, Vinayak; Lipson, Kenneth E; Scott, Edward W; Bryant, Andrew J

2018-01-01

Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown. In this study, we generated a transgenic mouse line in which the Ctgf gene was floxed and deleted in vascular endothelial cells that expressed Cre recombinase under the control of VE-Cadherin promoter (eCTGF KO mice). Lack of vascular endothelial-derived CTGF protected against the development of PH secondary to chronic hypoxia, as well as in another model of bleomycin-induced pulmonary hypertension. Importantly, attenuation of PH was associated with a decrease in infiltrating inflammatory cells expressing CD11b or integrin α M (ITGAM), a known adhesion receptor for CTGF, in the lungs of hypoxia-exposed eCTGF KO mice. Moreover, these pathological changes were associated with activation of-Rho GTPase family member-cell division control protein 42 homolog (Cdc42) signaling, known to be associated with alteration in endothelial barrier function. These data indicate that endothelial-specific deletion of CTGF results in protection against development of chronic-hypoxia induced PH. This protection is conferred by both a decrease in inflammatory cell recruitment to the lung, and a reduction in lung Cdc42 activity. Based on our studies, CTGF inhibitor treatment should be investigated in patients with PH associated with chronic hypoxia secondary to chronic lung disease.

Connective tissue growth factor and its regulation: a new element in diabetic glomerulosclerosis.

PubMed

Riser, B L; Cortes, P

2001-01-01

Connective tissue growth factor (CTGF), a member of the closely related CCN family of cytokines appears to be fibrotic in skin. To determine whether CTGF is implicated in diabetic glomerulosclerosis we studied cultured rat mesangial cells (MC) as well as kidney cortex and microdissected glomeruli from obese, diabetic db/db mice and their normal counterparts. Exposure of MC to rhCTGF significantly increased fibronectin and collagen type I secretion. Further, unstimulated MC expressed low levels of CTGF message and secreted minimal amounts of CTGF protein (36-38 kDa). However, exposure to TGF-beta, increased glucose concentrations, or cyclic mechanical strain, all causal factors in glomerulosclerosis, markedly induced the expression of CTGF transcripts. With all but mechanical strain there was a concomitant stimulation of CTGF protein secretion. TGF-beta also induced abundant quantities of a small molecular weight form of CTGF (18 kDa). The induction of CTGF protein by a high glucose concentration was mediated by TGF-beta, since a TGF-beta neutralizing antibody blocked this stimulation. In vivo studies using quantitative RT-PCR demonstrated that while CTGF transcripts were low in the glomeruli of control mice, expression was increased 27-fold after approximately 3.5 months of diabetes. These changes occurred early in diabetic nephropathy when mesangial expansion was mild, and interstitial disease and proteinuria were absent. A substantially reduced elevation of CTGF mRNA (2-fold) observed in whole kidney cortices indicted that the primary alteration of CTGF expression was in the glomerulus. These results suggest that CTGF upregulation is an important factor in the pathogenesis of mesangial matrix accumulation in both diabetic and non-diabetic glomerulosclerosis, acting downstream of TGF-beta.

[Etiological profile of secondary Raynaud's phenomenon in an internal medicine department. About 121 patients].

PubMed

Ben Salem, T; Tougorti, M; Bziouech, S; Lamloum, M; Khanfir, M; Ben Ghorbel, I; Houman, M H

2018-02-01

Raynaud's phenomenon is a reversible episodic vasospastic disorder triggered by cold or emotion. Two types of Raynaud's phenomenon were distinguished: Raynaud's disease and secondary Raynaud's phenomenon. The purpose of this study was to determine the etiologic profile of secondary Raynaud's phenomenon in an internal medicine department. A descriptive retrospective study including patients with secondary Raynaud's phenomenon followed in a tertiary internal medicine department between 2000 and 2013. We included 121 patients. The sex ratio M/F was 0.16. The mean age at the onset of Raynaud's phenomenon was 41.7 years. The average age of patients at the time of the etiologic diagnosis was 47.3 years. The mean delay between Raynaud's phenomenon onset and the first consultation was 41.33 months. Raynaud's phenomenon involved hands in all cases and feet in 16.10% of cases with a typical form in most cases (41.4%). Complications (digital ulcers and scars) were noted in 32.23% of cases. Nail fold capillaroscopy showed scleroderma pattern in 49.52% of patients. Antinuclear antibodies were positive in 88.49% of patients. Interstitial lung disease was reported in 54.04% of cases. Connective tissue diseases were diagnosed in 86.77% of patients. Other secondary Raynaud's phenomenon causes were vasculitis (6.61%), atherosclerosis (1.65%) and medical or professional causes (1.65%). The most frequent one cause systemic sclerosis (n=61, 98%) followed by systemic lupus erythematosus (11.57%) and primary Sjögren syndrome (6.61%). In our study, the Raynaud's phenomenon was most frequently secondary to connective tissue diseases. This may be a selection bias because our department is a third-line unit where patients are often referred for systemic disease suspicion. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

PubMed

Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie

2018-04-01

The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p < 0.001) higher collagen I content, a lower collagen III and elastin content, and a similar glycosaminoglycans (GAGs) content, in comparison with the NAV, as measured by ECM integrated density. However, the relative thickness of the main load-bearing structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p < 0.05) than in the longitudinal direction. This proved that both tissues were anisotropic. No statistically significant differences in UTS (ultimate tensile strength) values and in calculated bending stiffness values in the longitudinal or transversal direction were found between HP and NAV. Our study confirms that HP has an advantageous ECM biopolymeric structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

Undifferentiated Connective Tissue Disease

MedlinePlus

... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover.

PubMed

Jugdaohsingh, Ravin; Watson, Abigail I E; Pedro, Liliana D; Powell, Jonathan J

2015-06-01

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than previously estimated which could explain why absolute silicon deficiency is difficult to achieve but, when it is achieved in young growing animals, it results in stunted growth and abnormal development of bone and other connective tissues. Copyright © 2015. Published by Elsevier Inc.

The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover☆

PubMed Central

Jugdaohsingh, Ravin; Watson, Abigail I.E.; Pedro, Liliana D.; Powell, Jonathan J.

2015-01-01

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague–Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n = 8–10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2–6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague–Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than previously estimated which could explain why absolute silicon deficiency is difficult to achieve but, when it is achieved in young growing animals, it results in stunted growth and abnormal development of bone and other connective tissues. PMID:25687224

Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix.

PubMed

Kehlet, Stephanie N; Willumsen, Nicholas; Armbrecht, Gabriele; Dietzel, Roswitha; Brix, Susanne; Henriksen, Kim; Karsdal, Morten A

2018-01-01

The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small collagen fragments are released into the circulation, which act as important biomarkers in the study of certain tissue-related remodeling factors in health and disease. The aim of this study was to establish an age-related collagen turnover profile of the main collagens of the interstitial matrix (type I and III collagen) and basement membrane (type IV collagen) in healthy men and women. By using well-characterized competitive ELISA-assays, we assessed specific fragments of degraded (C1M, C3M, C4M) and formed (PINP, Pro-C3, P4NP7S) type I, III and IV collagen in serum from 617 healthy men and women ranging in ages from 22 to 86. Subjects were divided into 5-year age groups according to their sex and age. Groups were compared using Kruskal-Wallis adjusted for Dunn's multiple comparisons test and Mann-Whitney t-test. Age-specific changes in collagen turnover was most profound for type I collagen. PINP levels decreased in men with advancing age, whereas in women, the level decreased in early adulthood followed by an increase around the age of menopause (age 40-60). Sex-specific changes in type I, III and IV collagen turnover was present at the age around menopause (age 40-60) with women having an increased turnover. In summary, collagen turnover is affected by age and sex with the interstitial matrix and the basement membrane being differently regulated. The observed changes needs to be accounted for when measuring ECM related biomarkers in clinical studies.

Ultrafiltrate and microdialysis DL probe in vitro recoveries: electrolytes and metabolites

NASA Technical Reports Server (NTRS)

Janle, E. M.; Cregor, M.

1996-01-01

UF ultrafiltration and DL microdialysis probes are well-suited for sampling interstitial concentrations of ions and metabolites in peripheral tissue. The first step in utilization of membrane sampling techniques is to determine the recovery characteristics of the probes in vitro.

Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models

PubMed Central

Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz

2012-01-01

Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain–stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5–2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01–0.5 s−1 strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multimode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus. PMID:21207094

An experimental study of interstitial lung tissue classification in HRCT images using ANN and role of cost functions

NASA Astrophysics Data System (ADS)

Dash, Jatindra K.; Kale, Mandar; Mukhopadhyay, Sudipta; Khandelwal, Niranjan; Prabhakar, Nidhi; Garg, Mandeep; Kalra, Naveen

2017-03-01

In this paper, we investigate the effect of the error criteria used during a training phase of the artificial neural network (ANN) on the accuracy of the classifier for classification of lung tissues affected with Interstitial Lung Diseases (ILD). Mean square error (MSE) and the cross-entropy (CE) criteria are chosen being most popular choice in state-of-the-art implementations. The classification experiment performed on the six interstitial lung disease (ILD) patterns viz. Consolidation, Emphysema, Ground Glass Opacity, Micronodules, Fibrosis and Healthy from MedGIFT database. The texture features from an arbitrary region of interest (AROI) are extracted using Gabor filter. Two different neural networks are trained with the scaled conjugate gradient back propagation algorithm with MSE and CE error criteria function respectively for weight updation. Performance is evaluated in terms of average accuracy of these classifiers using 4 fold cross-validation. Each network is trained for five times for each fold with randomly initialized weight vectors and accuracies are computed. Significant improvement in classification accuracy is observed when ANN is trained by using CE (67.27%) as error function compared to MSE (63.60%). Moreover, standard deviation of the classification accuracy for the network trained with CE (6.69) error criteria is found less as compared to network trained with MSE (10.32) criteria.

CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

PubMed

Meziani, Lydia; Mondini, Michele; Petit, Benoît; Boissonnas, Alexandre; Thomas de Montpreville, Vincent; Mercier, Olaf; Vozenin, Marie-Catherine; Deutsch, Eric

2018-03-01

Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic.These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF. Copyright ©ERS 2018.

Three tropical seagrasses as potential bio-indicators to trace metals in Xincun Bay, Hainan Island, South China

NASA Astrophysics Data System (ADS)

Li, Lei; Huang, Xiaoping

2012-03-01

Concentrations of the trace metals Cu, Cd, Pb, and Zn were measured in seawater, rhizosphere sediments, interstitial water, and the tissues of three tropical species of seagrasses ( Thalassia hemprichii, Enhalus acoroides and Cymodocea rotundata) from Xincun Bay of Hainan Island, South China. We analyzed different environmental compartments and the highest concentrations of Pb and Zn were found in the interstitial and seawater. The concentrations of Cd and Zn were significantly higher in blades compared with roots or rhizomes in T. hemprichii and E. acoroides, respectively. A metal pollution index (MPI) demonstrated that sediment, interstitial water, and seagrasses in the sites located nearest anthropogenic sources of pollution had the most abundant metal concentrations. There was obvious seasonal variation of these metals in the three seagrasses with higher concentrations of Cu, Pb and Zn in January and Cd in July. Furthermore, the relationships between metal concentrations in seagrasses and environmental compartments were positively correlated significantly. The bioconcentration factors (BCF) demonstrated that Cd from the tissues of the three seagrasses might be absorbed from the sediment by the roots. However, for C. rotundata, Zn is likely to be derived from the seawater through its blades. Therefore, the blades of T. hemprichii, E. acoroides and C. rotundata are potential bio-indicators to Cd content in sediment, and additionally Zn content ( C. rotundata only) in seawater.

Radiotherapy in patients with connective tissue diseases.

PubMed

Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

2016-03-01

The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

PubMed

Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

2014-01-01

Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Electrostatic, elastic and hydration-dependent interactions in dermis influencing volume exclusion and macromolecular transport.

PubMed

Øien, Alf H; Wiig, Helge

2016-07-07

Interstitial exclusion refers to the limitation of space available for plasma proteins and other macromolecules based on collagen and negatively charged glycosaminoglycans (GAGs) in the interstitial space. It is of particular importance to interstitial fluid and plasma volume regulation. Here we present a novel mechanical and mathematical model of the dynamic interactions of structural elements within the interstitium of the dermis at the microscopic level that may explain volume exclusion of charged and neutral macroparticles. At this level, the interstitium is considered to consist of elements called extracellular matrix (ECM) cells, again containing two main interacting structural components on a fluid background including anions and cations setting up osmotic forces: one smaller GAG component, having an intrinsic expansive electric force, and one bigger collagen component, having an intrinsic elastic force. Because of size differences, the GAG component interacts with a fraction of the collagen component only at normal hydration. This fraction, however, increases with rising hydration as a consequence of the modeled form of the interaction force between the GAGs and collagen. Collagen is locally displaced at variable degrees as hydration changes. Two models of GAGs are considered, having largely different geometries which demands different, but related, forms of GAG-collagen interaction forces. The effects of variable fixed charges on GAGs and of GAG density in tissue are evaluated taking into account observed volume exclusion properties of charged macromolecules as a function of tissue hydration. The presented models may improve our biophysical understanding of acting forces influencing tissue fluid dynamics. Such knowledge is significant when evaluating the transport of electrically charged and neutral macromolecules into and through the interstitium, and therefore to drug uptake and the therapeutic effects of macromolecular agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors

PubMed Central

2014-01-01

Background The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor. Methods The advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated. Results Sensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible. Conclusions This study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection. PMID:24987457

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy.

PubMed

Blyth, Benjamin J; Kakinuma, Shizuko; Sunaoshi, Masaaki; Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Ogawa, Kanae; Shirakami, Ayana; Shang, Yi; Tsuruoka, Chizuru; Nishimura, Mayumi; Shimada, Yoshiya

2015-01-01

Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV x μm(-1)) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second cancer risk in carbon ion radiotherapy patients.

[Muscles and connective tissue: histology].

PubMed

Delage, J-P

2012-10-01

Here, we give some comments about the DVD movies "Muscle Attitudes" from Endovivo productions, the movies up lighting some loss in the attention given to studies on the connective tissue, and especially them into muscles. The main characteristics of the different components in the intra-muscular connective tissue (perimysium, endomysium, epimysium) are shown here with special references to their ordered architecture and special references to their spatial distributions. This connective tissue is abundant into the muscles and is in continuity with the muscles in vicinity, with their tendons and their sheath, sticking the whole on skin. This connective tissue has also very abundant connections on the muscles fibres. It is then assumed that the connective tissue sticks every organs or cells of the locomotion system. Considering the elastic properties of the collagen fibres which are the most abundant component of connective tissue, it is possible to up light a panel of connective tissue associated functions such as the transmission of muscle contractions or the regulation of protein and energetic muscles metabolism. Copyright © 2012. Published by Elsevier SAS.

Studies of a novel photosensitizer Pd-bacteriopheophorbide (Tookad) for the prostate cancer PDT in canine model

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Luck, David L.; Beckers, Jill; Hetzel, Fred W.

2003-12-01

Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

Nanoscale viscoelasticity of extracellular matrix proteins in soft tissues: A multiscale approach.

PubMed

Miri, Amir K; Heris, Hossein K; Mongeau, Luc; Javid, Farhad

2014-02-01

It is hypothesized that the bulk viscoelasticity of soft tissues is determined by two length-scale-dependent mechanisms: the time-dependent response of the extracellular matrix (ECM) proteins at the nanometer scale and the biophysical interactions between the ECM solid structure and interstitial fluid at the micrometer scale. The latter is governed by poroelasticity theory assuming free motion of the interstitial fluid within the porous ECM structure. In a recent study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013. J. Mech. Behav. Biomed. Mater.), atomic force microscopy was used to measure the response of porcine vocal folds to a creep loading and a 50-nm sinusoidal oscillation. A constitutive model was calibrated and verified using a finite element model to accurately predict the nanoscale viscoelastic moduli of ECM. A generally good correlation was obtained between the predicted variation of the viscoelastic moduli with depth and that of hyaluronic acids in vocal fold tissue. We conclude that hyaluronic acids may regulate vocal fold viscoelasticity. The proposed methodology offers a characterization tool for biomaterials used in vocal fold augmentations. © 2013 Elsevier Ltd. All rights reserved.

Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models.

PubMed

Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz; Demer, Joseph L

2011-12-01

Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain-stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5-2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01-0.5 s(-1) strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multi-mode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus.

Histopathological and Digital Morphometrical Evaluation of Uterine Leiomyoma in Brazilian Women

PubMed Central

da Silva, Ana Paula Fernandes; Mello, Luciano de Albuquerque; dos Santos, Erlene Roberta Ribeiro; Paz, Silvania Tavares; Cavalcanti, Carmelita Lima Bezerra; de Melo-Junior, Mario Ribeiro

2016-01-01

The current study aims to evaluate histopathological and digital morphometrical aspects associated with uterine leiomyomas in one hundred and fifty (150) patients diagnosed with leiomyoma. Uterine tissues were subjected to the histopathological and digital morphometric analyses of the interstitial collagen distribution. The analysis of medical records indicates that most of the women diagnosed with uterine leiomyomas (68.7%) are between 37 and 48 years old. As for the anatomic location of the tumors, approximately 61.4% of the patients had intramural and subserosal lesions. In 50% of the studied cases, the patients developed uterine leiomyomatosis (with more than eight tumors). As for the morphometric study, the average size of the interstitial collagen distribution held approximately 28.53% of the capture area, whereas it was of 7.43% in the normal tissue adjacent to the tumor. Another important aspect observed in the current study was the high rate of young women subjected to total hysterectomy, a fact that resulted in early and definitive sterility. PMID:27293441

Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice.

PubMed

Ishida, O; Maruyama, K; Sasaki, K; Iwatsuru, M

1999-11-10

We have examined the size dependence of extravasation and interstitial localization of polyethyleneglycol-coated liposomes (PEG-liposomes) in the solid tumor tissue by means of electron microscopic observation. Liposomes composed of distearoyl phosphatidylcholine, cholesterol and distearoylphosphatidylethanolamine derivative of polyethyleneglycol (PEG) were prepared in various size ranges. PEG-liposomes with an average diameter of 100-200 nm showed the most prolonged circulation time and the greatest tumor accumulation in all the solid tumors employed in this experiment. Although large PEG-liposomes with a diameter of 400 nm showed a short circulation time in normal mice, the results in splenectomized mice indicated that they do have an intrinsic prolonged circulation character in vivo. However, large PEG-liposomes could not extravasate into solid tumor tissue. These results indicate that the size of liposomes is critical for extravasation. The electron microscopic observations revealed the almost exclusive engulfment of extravasated liposomes by tumor-associated macrophages; very few were taken up by tumor cells.

Mapping oxygen concentration in the awake mouse brain

PubMed Central

Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

2016-01-01

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism. DOI: http://dx.doi.org/10.7554/eLife.12024.001 PMID:26836304

Mapping oxygen concentration in the awake mouse brain.

PubMed

Lyons, Declan G; Parpaleix, Alexandre; Roche, Morgane; Charpak, Serge

2016-02-02

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism.

Robust G2 pausing of adult stem cells in Hydra.

PubMed

Buzgariu, Wanda; Crescenzi, Marco; Galliot, Brigitte

2014-01-01

Hydra is a freshwater hydrozoan polyp that constantly renews its two tissue layers thanks to three distinct stem cell populations that cannot replace each other, epithelial ectodermal, epithelial endodermal, and multipotent interstitial. These adult stem cells, located in the central body column, exhibit different cycling paces, slow for the epithelial, fast for the interstitial. To monitor the changes in cell cycling in Hydra, we established a fast and efficient flow cytometry procedure, which we validated by confirming previous findings, as the Nocodazole-induced reversible arrest of cell cycling in G2/M, and the mitogenic signal provided by feeding. Then to dissect the cycling and differentiation behaviors of the interstitial stem cells, we used the AEP_cnnos1 and AEP_Icy1 transgenic lines that constitutively express GFP in this lineage. For the epithelial lineages we used the sf-1 strain that rapidly eliminates the fast cycling cells upon heat-shock and progressively becomes epithelial. This study evidences similar cycling patterns for the interstitial and epithelial stem cells, which all alternate between the G2 and S-phases traversing a minimal G1-phase. We also found interstitial progenitors with a shorter G2 that pause in G1/G0. At the animal extremities, most cells no longer cycle, the epithelial cells terminally differentiate in G2 and the interstitial progenitors in G1/G0. At the apical pole ~80% cells are post-mitotic differentiated cells, reflecting the higher density of neurons and nematocytes in this region. We discuss how the robust G2 pausing of stem cells, maintained over weeks of starvation, may contribute to regeneration. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues

PubMed Central

Nassari, Sonya; Duprez, Delphine; Fournier-Thibault, Claire

2017-01-01

Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult. PMID:28386539

Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues.

PubMed

Nassari, Sonya; Duprez, Delphine; Fournier-Thibault, Claire

2017-01-01

Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.

Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

2005-04-01

Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

Intravital third harmonic generation microscopy of collective melanoma cell invasion

PubMed Central

Weigelin, Bettina; Bakker, Gert-Jan; Friedl, Peter

2012-01-01

Cancer cell invasion is an adaptive process based on cell-intrinsic properties to migrate individually or collectively, and their adaptation to encountered tissue structure acting as barrier or providing guidance. Whereas molecular and physical mechanisms of cancer invasion are well-studied in 3D in vitro models, their topographic relevance, classification and validation toward interstitial tissue organization in vivo remain incomplete. Using combined intravital third and second harmonic generation (THG, SHG), and three-channel fluorescence microscopy in live tumors, we here map B16F10 melanoma invasion into the dermis with up to 600 µm penetration depth and reconstruct both invasion mode and tissue tracks to establish invasion routes and outcome. B16F10 cells preferentially develop adaptive invasion patterns along preformed tracks of complex, multi-interface topography, combining single-cell and collective migration modes, without immediate anatomic tissue remodeling or destruction. The data suggest that the dimensionality (1D, 2D, 3D) of tissue interfaces determines the microanatomy exploited by invading tumor cells, emphasizing non-destructive migration along microchannels coupled to contact guidance as key invasion mechanisms. THG imaging further detected the presence and interstitial dynamics of tumor-associated microparticles with submicron resolution, revealing tumor-imposed conditioning of the microenvironment. These topographic findings establish combined THG, SHG and fluorescence microscopy in intravital tumor biology and provide a template for rational in vitro model development and context-dependent molecular classification of invasion modes and routes. PMID:29607252

Ultrasonic Characterization of the Linear Elastic Properties of Myocardium and Other Anisotropic Soft Tissues

NASA Astrophysics Data System (ADS)

Hoffmeister, Brentley Keith

1995-01-01

This thesis seeks to contribute to a better understanding of the physics of interaction of ultrasonic waves with inhomogeneous and anisotropic media, one example of which is the human heart. The clinical success of echocardiography has generated a considerable interest in the development of ultrasonic techniques to measure the elastic properties of heart tissue. It is hypothesized that the elastic properties of myocardium are influenced by the interstitial content and organization of collagen. Collagen, which is the main component of tendon, interconnects the muscle cells of the heart to form locally unidirectional myofibers. This thesis therefore employs ultrasonic techniques to characterize the linear elastic properties of both heart and tendon. The linear elastic properties of tissues possessing a unidirectional arrangement of fibers may be described in terms of five independent elastic stiffness coefficients. Three of these coefficients were determined for formalin fixed specimens of bovine Achilles tendon and human myocardium by measuring the velocity of longitudinal mode ultrasonic pulses as a function of angle of propagation relative to the fiber axis of the tissue. The remaining two coefficients were determined by measuring the velocity of transverse mode ultrasonic waves through these tissues. To overcome technical difficulties associated with the extremely high attenuation of transverse mode waves at low megahertz frequencies, a novel measurement system was developed based on the sampled continuous wave technique. Results of these measurements were used to assess the influence of interstitial collagen, and to model the mechanical properties of heart wall.

Changes in the dielectric properties of ex vivo bovine liver during microwave thermal ablation at 2.45 GHz

NASA Astrophysics Data System (ADS)

Lopresto, Vanni; Pinto, Rosanna; Lovisolo, Giorgio A.; Cavagnaro, Marta

2012-04-01

In microwave thermal ablation (MTA) therapy, the dielectric properties of the target tissue play an important role in determining the radiation properties of the microwave ablation antenna. In this work, the ex vivo dielectric properties of bovine liver were experimentally characterized as a function of the temperature during MTA at the frequency of 2.45 GHz. The obtained data were compared with measurements performed at the end of the MTA treatment, and considering the heating achieved with a temperature-controlled water bath. Finally, measured data were used to perform a numerical study evaluating the effects of changes in tissue's dielectric properties during the MTA treatment on the radiation properties of a microwave interstitial ablation antenna, as well as on the obtained thermal lesion. Results evidenced a significant decrease of both relative permittivity (about 38%) and electric conductivity (about 33%) in the tissue during treatment as the temperature increased to over 60 °C, with a dramatic drop when the temperature approached 100 °C. Moreover, the numerical study evidenced that changes in tissue's dielectric properties during the MTA treatment affect the distribution of the power absorbed by the tissue (specific absorption rate—SAR, W kg-1) surrounding the microwave interstitial ablation antenna, leading to a peak SAR up to 20% lower, as well as to a thermal lesion up to 8% longer. This work may represent a preliminary step towards the future development of a procedure for MTA treatment planning.

Fluorescein angiography of the bladder: technique and relevance to bladder cancer and interstitial cystitis patients.

PubMed

Zimmern, P E; Laub, D; Leach, G E

1995-07-01

Fluorescein angiography has been used in the study of bleeding vessels, neovascularity, tumors and ischemic tissues in a variety of disorders. This pilot study was designed to evaluate the feasibility, safety and relevance of this interesting technology for the evaluation of bladder wall vessels in patients with interstitial cystitis and bladder cancer. Five patients with National Institutes of Health defined interstitial cystitis symptoms and 10 with bladder cancer were studied during cytoscopy while they were under general anesthesia. A yellow-green barrier filter (520 nm.) was placed over the cystoscope eyepiece and a blue exciter filter (465 nm.) was attached to the light source. Patients received a 5 ml. bolus of 10% fluorescein intravenously. After hydrodistension, glomerulations in interstitial cystitis patients were more prominent with fluorescein angiography and occurred in the venule phase. Areas of papillary transitional cell tumor and carcinoma in situ developed a brilliant yellow-green fluorescence. Adjacent normal urothelium was nonfluorescent and provided a contrasting dark background facilitating the detection of all lesions. No allergic reaction or other adverse effect related to the fluorescein injection was observed. These unique observations in a limited number of patients suggest that fluorescein angiography of the bladder is a safe and simple procedure. This preliminary report underscores the relevance of fluorescein angiography in the detection of bladder tumor and offers a new approach to the evaluation of bladder wall vessels in interstitial cystitis patients.

Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

PubMed

Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

2012-09-01

Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

MRI contrast agent concentration and tumor interstitial fluid pressure.

PubMed

Liu, L J; Schlesinger, M

2016-10-07

The present work describes the relationship between tumor interstitial fluid pressure (TIFP) and the concentration of contrast agent for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We predict the spatial distribution of TIFP based on that of contrast agent concentration. We also discuss the cases for estimating tumor interstitial volume fraction (void fraction or porosity of porous medium), ve, and contrast volume transfer constant, K(trans), by measuring the ratio of contrast agent concentration in tissue to that in plasma. A linear fluid velocity distribution may reflect a quadratic function of TIFP distribution and lead to a practical method for TIFP estimation. To calculate TIFP, the parameters or variables should preferably be measured along the direction of the linear fluid velocity (this is in the same direction as the gray value distribution of the image, which is also linear). This method may simplify the calculation for estimating TIFP. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

PDGF-BB induces PRMT1 expression through ERK1/2 dependent STAT1 activation and regulates remodeling in primary human lung fibroblasts.

PubMed

Sun, Qingzhu; Liu, Li; Mandal, Jyotshna; Molino, Antonio; Stolz, Daiana; Tamm, Michael; Lu, Shemin; Roth, Michael

2016-04-01

Tissue remodeling of sub-epithelial mesenchymal cells is a major pathology occurring in chronic obstructive pulmonary disease (COPD) and asthma. Fibroblasts, as a major source of interstitial connective tissue extracellular matrix, contribute to the fibrotic and inflammatory changes in these airways diseases. Previously, we described that protein arginine methyltransferase-1 (PRMT1) participates in airway remodeling in a rat model of pulmonary inflammation. In this study we investigated the mechanism by which PDGF-BB regulates PRMT1 in primary lung fibroblasts, isolated from human lung biopsies. Fibroblasts were stimulated with PDGF-BB for up-to 48h and the regulatory and activation of signaling pathways controlling PRMT1 expression were determined. PRMT1 was localized by immuno-histochemistry in human lung tissue sections and by immunofluorescence in isolated fibroblasts. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI1. ERK1/2 mitogen activated protein kinase (MAPK) was blocked by PD98059, p38 MAPK by SB203580, and STAT1 by small interference (si) RNA treatment. The results showed that PDGF-BB significantly increased PRMT1 expression after 1h lasting over 48h, through ERK1/2 MAPK and STAT1 signaling. The inhibition of ERK1/2 MAPK or of PRMT1 activity decreased PDGF-BB induced fibroblast proliferation, COX2 production, collagen-1A1 secretion, and fibronectin production. These findings suggest that PRMT1 is a central regulator of tissue remodeling and that the signaling sequence controlling its expression in primary human lung fibroblast is PDGF-ERK-STAT1. Therefore, PRMT1 presents a novel therapeutic and diagnostic target for the control of airway wall remodeling in chronic lung diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

An Ultrasound Surface Wave Technique for Assessing Skin and Lung Diseases.

PubMed

Zhang, Xiaoming; Zhou, Boran; Kalra, Sanjay; Bartholmai, Brian; Greenleaf, James; Osborn, Thomas

2018-02-01

Systemic sclerosis (SSc) is a multi-organ connective tissue disease characterized by immune dysregulation and organ fibrosis. Severe organ involvement, especially of the skin and lung, is the cause of morbidity and mortality in SSc. Interstitial lung disease (ILD) includes multiple lung disorders in which the lung tissue is fibrotic and stiffened. The purpose of this study was to translate ultrasound surface wave elastography (USWE) for assessing patients with SSc and/or ILD via measuring surface wave speeds of both skin and superficial lung tissue. Forty-one patients with both SSc and ILD and 30 healthy patients were enrolled in this study. An external harmonic vibration was used to generate the wave propagation on the skin or lung. Three excitation frequencies of 100, 150 and 200 Hz were used. An ultrasound probe was used to measure the wave propagation in the tissue non-invasively. Surface wave speeds were measured on the forearm and upper arm of both left and right arm, as well as the upper and lower lungs, through six intercostal spaces of patients and healthy patients. Viscoelasticity of the skin was calculated by the wave speed dispersion with frequency using the Voigt model. The magnitudes of surface wave speed and viscoelasticity of patients' skin were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. The surface wave speeds of patients' lung were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. USWE is a non-invasive and non-ionizing technique for measuring both skin and lung surface wave speed and may be useful for quantitative assessment of SSc and/or ILD. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

PubMed

Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

PubMed Central

Taoka, Toshiaki; Naganawa, Shinji

2018-01-01

After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

Conformal needle-based ultrasound ablation using EM-tracked conebeam CT image guidance

NASA Astrophysics Data System (ADS)

Burdette, E. Clif; Banovac, Filip; Diederich, Chris J.; Cheng, Patrick; Wilson, Emmanuel; Cleary, Kevin R.

2011-03-01

Numerous studies have demonstrated the efficacy of interstitial ablative approaches for the treatment of renal and hepatic tumors. Despite these promising results, current systems remain highly dependent on operator skill, and cannot treat many tumors because there is little control of the size and shape of the zone of necrosis, and no control over ablator trajectory within tissue once insertion has taken place. Additionally, tissue deformation and target motion make it extremely difficult to accurately place the ablator device into the target. Irregularly shaped target volumes typically require multiple insertions and several sequential thermal ablation procedures. This study demonstrated feasibility of spatially tracked image-guided conformal ultrasound (US) ablation for percutaneous directional ablation of diseased tissue. Tissue was prepared by suturing the liver within a pig belly and 1mm BBs placed to serve as needle targets. The image guided system used integrated electromagnetic tracking and cone-beam CT (CBCT) with conformable needlebased high-intensity US ablation in the interventional suite. Tomographic images from cone beam CT were transferred electronically to the image-guided tracking system (IGSTK). Paired-point registration was used to register the target specimen to CT images and enable navigation. Path planning is done by selecting the target BB on the GUI of the realtime tracking system and determining skin entry location until an optimal path is selected. Power was applied to create the desired ablation extent within 7-10 minutes at a thermal dose (>300eqm43). The system was successfully used to place the US ablator in planned target locations within ex-vivo kidney and liver through percutaneous access. Targeting accuracy was 3-4 mm. Sectioned specimens demonstrated uniform ablation within the planned target zone. Subsequent experiments were conducted for multiple ablator positions based upon treatment planning simulations. Ablation zones in liver were 73cc, 84cc, and 140cc for 3, 4, and 5 placements, respectively. These experiments demonstrate the feasibility of combining real-time spatially tracked image guidance with directional interstitial ultrasound ablation. Interstitial ultrasound ablation delivered on multiple needles permit the size and shape of the ablation zone to be "sculpted" by modifying the angle and intensity of the active US elements in the array. This paper summarizes the design and development of the first system incorporating thermal treatment planning and integration of a novel interstitial acoustic ablation device with integrated 3D electromagnetic tracking and guidance strategy.

Towards the Early Detection of Breast Cancer in Young Women

DTIC Science & Technology

2006-10-01

approach. 4. Poroelastic model for tissue deformation: We have implemented the model of Netti et al. in a finite element program in order to simulate...changes would not be expected. 44Interstitial Fluid Flow 5. Conclusions A poroelastic model that includes the effects of fluid flow and the possibility of...images to produce a displacement field. Using this displacement field, and an assumed linear elastic model for the tissue, an inverse problem is solved

Development of transrectal diffuse optical tomography combined with 3D-transrectal ultrasound imaging to monitor the photocoagulation front during interstitial photothermal therapy of primary focal prostate cancer

NASA Astrophysics Data System (ADS)

He, Jie; Weersink, Robert; Veilleux, Israel; Mayo, Kenwrick; Zhang, Anqi; Piao, Daqing; Alam, Adeel; Trachtenberg, John; Wilson, Brian C.

2013-03-01

Interstitial near-infrared laser thermal therapy (LITT) is currently undergoing clinical trials as an alternative to watchful waiting or radical surgery in patients with low-risk focal prostate cancer. Currently, we use magnetic resonance image (MRI)-based thermography to monitor treatment delivery and determine indirectly the completeness of the target tissue destruction while avoiding damage to adjacent normal tissues, particularly the rectal wall. However, incomplete tumor destruction has occurred in a significant fraction of patients due to premature termination of treatment, since the photocoagulation zone is not directly observed. Hence, we are developing transrectal diffuse optical tomography (TRDOT), in combination with transrectal 3D ultrasound (3D-TRUS), to address his limitation. This is based on the large changes in optical scattering expected upon tissue coagulation. Here, we present forward simulations of a growing coagulated lesion with optical scattering contrast, using an established finite element analysis software platform (NIRFAST). The simulations were validated in tissue-simulating phantoms, with measurements acquired by a state-of-the-art continuous wave (CW) TRDOT system and a recently assembled bench-top CW-DOT system, with specific source-detector configurations. Two image reconstruction schemes were investigated and evaluated, specifically for the accurate delineation of the posterior boundary of the coagulation zone as the critical parameter for treatment guidance in this clinical application.

SU-E-T-574: Fessiblity of Using the Calypso System for HDR Interstitial Catheter Reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J S; Ma, C

2014-06-01

Purpose: It is always a challenge to reconstruct the interstitial catheter for high dose rate (HDR) brachytherapy on patient CT or MR images. This work aims to investigate the feasibility of using the Calypso system (Varian Medical, CA) for HDR catheter reconstruction utilizing its accuracy on tracking the electromagnetic transponder location. Methods: Experiment was done with a phantom that has a HDR interstitial catheter embedded inside. CT scan with a slice thickness of 1.25 mm was taken for this phantom with two Calypso beacon transponders in the catheter. The two transponders were connected with a wire. The Calypso system wasmore » used to record the beacon transponders’ location in real time when they were gently pulled out with the wire. The initial locations of the beacon transponders were used for registration with the CT image and the detected transponder locations were used for the catheter path reconstruction. The reconstructed catheter path was validated on the CT image. Results: The HDR interstitial catheter was successfully reconstructed based on the transponders’ coordinates recorded by the Calypso system in real time when the transponders were pulled in the catheter. After registration with the CT image, the shape and location of the reconstructed catheter are evaluated against the CT image and the result shows an accuracy of 2 mm anywhere in the Calypso detectable region which is within a 10 cm X 10 cm X 10 cm cubic box for the current system. Conclusion: It is feasible to use the Calypso system for HDR interstitial catheter reconstruction. The obstacle for its clinical usage is the size of the beacon transponder whose diameter is bigger than most of the interstitial catheters used in clinic. Developing smaller transponders and supporting software and hardware for this application is necessary before it can be adopted for clinical use.« less

Tissue types (image)

MedlinePlus

... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

Effect of tin etiopurpurin and light on the canine prostate

NASA Astrophysics Data System (ADS)

Selman, Steven H.; Keck, Rick W.; Doiron, Daniel R.

1995-03-01

A series of experiments was undertaken to determine the effects of the combination of light and the tissue photosensitizer, tin etiopurpurin, on the canine prostate. Mongrel dogs were injected intravenously with 1.0 mg/kg of photosensitizer twenty-four hours prior to light delivery. Laser light, 660 nm, was administered either transurethrally or interstitially and tissue effects were assessed by histopathologic examination. Both techniques of light delivery resulted in hemorrhagic necrosis of the surrounding tissue. Photodynamic therapy may offer a novel approach to the treatment of both benign and malignant diseases of the prostate.

Pulmonary Function and Survival in Idiopathic vs Secondary Usual Interstitial Pneumonia

PubMed Central

Strand, Matthew J.; Sprunger, David; Cosgrove, Gregory P.; Fernandez-Perez, Evans R.; Frankel, Stephen K.; Huie, Tristan J.; Olson, Amy L.; Solomon, Joshua; Brown, Kevin K.

2014-01-01

BACKGROUND: The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS: We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco %), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS: There were no significant differences between groups in longitudinal changes in FVC % or Dlco % up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco % per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS: Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF. PMID:24700149

Interstitial Lung Disease in India. Results of a Prospective Registry.

PubMed

Singh, Sheetu; Collins, Bridget F; Sharma, Bharat B; Joshi, Jyotsna M; Talwar, Deepak; Katiyar, Sandeep; Singh, Nishtha; Ho, Lawrence; Samaria, Jai Kumar; Bhattacharya, Parthasarathi; Gupta, Rakesh; Chaudhari, Sudhir; Singh, Tejraj; Moond, Vijay; Pipavath, Sudhakar; Ahuja, Jitesh; Chetambath, Ravindran; Ghoshal, Aloke G; Jain, Nirmal K; Devi, H J Gayathri; Kant, Surya; Koul, Parvaiz; Dhar, Raja; Swarnakar, Rajesh; Sharma, Surendra K; Roy, Dhrubajyoti J; Sarmah, Kripesh R; Jankharia, Bhavin; Schmidt, Rodney; Katiyar, Santosh K; Jindal, Arpita; Mangal, Daya K; Singh, Virendra; Raghu, Ganesh

2017-03-15

Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

Chymase inhibition prevents fibronectin and myofibrillar loss and improves cardiomyocyte function and LV torsion angle in dogs with isolated mitral regurgitation.

PubMed

Pat, Betty; Chen, Yuanwen; Killingsworth, Cheryl; Gladden, James D; Shi, Ke; Zheng, Junying; Powell, Pamela C; Walcott, Greg; Ahmed, Mustafa I; Gupta, Himanshu; Desai, Ravi; Wei, Chih-Chang; Hase, Naoki; Kobayashi, Tsunefumi; Sabri, Abdelkarim; Granzier, Henk; Denney, Thomas; Tillson, Michael; Dillon, A Ray; Husain, Ahsan; Dell'italia, Louis J

2010-10-12

The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with a failure of CI to improve a 25% decrease in interstitial collagen in MR. However, LV cardiomyocyte fractional shortening was decreased in MR versus normal dogs (3.71±0.24% versus 4.81±0.31%; P<0.05) and normalized in MR+CI dogs (4.85±0.44%). MRI with tissue tagging demonstrated an increase in LV torsion angle in MR+CI versus MR dogs. CI normalized the significant decrease in fibronectin and FAK phosphorylation and prevented cardiomyocyte myofibrillar degeneration in MR dogs. In addition, total titin and its stiffer isoform were increased in the LV epicardium and paralleled the changes in fibronectin and FAK phosphorylation in MR+CI dogs. These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can adversely affect cardiomyocyte myofibrillar structure and function. The greater effect of CI on epicardial versus endocardial titin and noncollagen cell surface proteins may be responsible for the increase in torsion angle in chronic MR.

FSP1-specific SMAD2 knockout in renal tubular, endothelial, and interstitial cells reduces fibrosis and epithelial-to-mesenchymal transition in murine STZ-induced diabetic nephropathy.

PubMed

Loeffler, Ivonne; Liebisch, Marita; Allert, Stefanie; Kunisch, Elke; Kinne, Raimund W; Wolf, Gunter

2018-04-01

Extracellular matrix deposition during tubulointerstitial fibrosis (TIF), a central pathological process in patients with diabetic nephropathy (DN), is driven by locally activated, disease-relevant myofibroblasts. Myofibroblasts can arise from various cellular sources, e.g., tubular epithelial cells via a process named epithelial-to-mesenchymal transition (EMT). Transforming growth factor beta 1 (TGF-β1) and its downstream Smad signaling play a critical role in both TIF and EMT. Whereas Smad3 is one central mediator, the role of the other prominently expressed variant, Smad2, is not completely understood. In this study, we sought to analyze the role of renal Smad2 in the development of TIF and EMT during streptozotocin-induced DN by using a fibroblast-specific protein 1 (FSP1)-promotor-driven SMAD2 knockout mouse model with decreased tubular, endothelial, and interstitial Smad2 expression. In contrast to wild-type diabetic mice, diabetic SMAD2 knockout mice showed the following features: (1) significantly reduced DN and TIF (shown by KIM1 expression; periodic acid Schiff staining; collagen I and III, fibronectin, and connective tissue growth factor deposition); (2) significantly reduced tubular EMT-like changes (e.g., altered Snail1, E-cadherin, matrix metalloproteinase 2, and vimentin deposition); and (3) significantly decreased expression of myofibroblast markers (α-smooth muscle actin, FSP1). As one mechanism for the protection against diabetes-induced TIF and EMT, decreased Smad3 protein levels and, as a possible consequence, reduced TGF-β1 levels were observed in diabetic SMAD2 knockout mice. Our findings thus support the important role of Smad2 for pro-fibrotic TGF-β/Smad3 signaling in experimental DN.

Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways

PubMed Central

Zhang, Changyi; Zhou, Guichi; Chen, Yezeng; Liu, Sizheng; Chen, Fen; Xie, Lichun; Wang, Wei; Zhang, Yonggang; Wang, Tianyou; Lai, Xiulan; Ma, Lian

2018-01-01

Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord-derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin-induced rat model of DCM. Male Lewis rats (aged 8-weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1×106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle-injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF-α, extracellular-signal regulated kinase 1/2 (ERK1/2) and TGF-β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF-α and the TGF-β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM. PMID:29115435

What can the microstructure of stones tell us?

PubMed Central

Williams, James C.; Worcester, Elaine; Lingeman, James E.

2016-01-01

How stones are retained within the kidney while small in size is still not fully understood. In this paper we show two examples of how stones are retained during early growth: One is growth on Randall’s (interstitial) plaque, and the other is growth on mineral that has formed as a luminal plug in a terminal collecting duct. These two mechanisms of stone retention during early growth have distinctive morphologic features that can be seen by methods that show the microscopic structure of the stones. Stones growing on Randall’s plaque display an apatite region that is typically not large in size (less than 0.5 mm across) but which usually shows luminal spaces, which are signs of its origin in the connective tissue of the papilla. Stones growing on ductal plugs also show attachment to a piece of apatite, but the apatite regions are typically larger (often >1 mm long and >0.5 mm wide), and they are solid, without spaces running through them. We propose that knowing the mechanisms of stone retention during early stone formation could allow for better treatment of stone diseases. PMID:27913855

Expression of peroxisome proliferator-activated receptor alpha messenger ribonucleic acid and protein in human and rat testis.

PubMed

Schultz, R; Yan, W; Toppari, J; Völkl, A; Gustafsson, J A; Pelto-Huikko, M

1999-07-01

Peroxisome proliferator-activated receptor a (PPARalpha), a member of the steroid hormone receptor superfamily, has been linked to lipid homeostasis and tumorigenesis in tissues with high expression of receptor protein. On the other hand, the role of PPARalpha in tissues with a lower expression is not well known. Here we demonstrate the localization of PPARalpha messenger RNA (mRNA) and protein in developing and adult rat testis. Additionally, we demonstrate the expression of PPARalpha protein in adult human testis. Our experiments with Northern analysis, in situ hybridization and immunocytochemistry reveal a complex distribution of PPARalpha in tubular and interstitial cells of both adult and developing rat testis. The overall expression is rather low but may be modified by exogenous or endogenous stimuli. An up-regulation of PPARalpha mRNA could be observed after stimulation with FSH. In the developing rat testis, a clear expression of PPARalpha mRNA was present from the first days after birth. Additionally, PPARalpha mRNA and protein increased toward adulthood. In adult human testis PPARalpha immunoreactivity (IR) was present in interstitial Leydig cells and tubular cells. In the seminiferous epithelium of adult human testis the expression of PPARalpha-IR could be seen in meiotic spermatocytes, spermatids and myoid peritubular cells. The findings of our study suggest that PPARalpha may be involved in the regulation of growth and differentiation of tubular and interstitial cells in rat and human testis.

Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

PubMed

Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

2018-01-03

Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non-cyclophosphamide-containing therapies for at least six months, with follow-up of at least 12 months from the start of treatment. We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were change in lung function (change in forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted), adverse events, and health-related quality of life measures. Secondary outcomes included all-cause mortality, dyspnoea, cough, and functional exercise testing. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and created 'Summary of findings' tables. We included in the analysis four trials with 495 participants (most with systemic sclerosis). We formed two separate comparisons: cyclophosphamide versus placebo (two trials, 195 participants) and cyclophosphamide versus mycophenolate (two trials, 300 participants). We found evidence to be of low quality, as dropout rates were high in the intervention groups, and as we noted a wide confidence interval around the effect with small differences, which affected the precision of results.The data demonstrates significant improvement in lung function with cyclophosphamide compared with placebo (post-treatment FVC % mean difference (MD) 2.83, 95% confidence interval (CI) 0.80 to 4.87; P = 0.006) but no significant difference in post-treatment DLCO (% MD -1.68, 95% CI -4.37 to 1.02; P = 0.22; two trials, 182 participants).Risk of adverse effects was increased in the cyclophosphamide treatment groups compared with the placebo groups, in particular, haematuria, leukopenia, and nausea, leading to a higher rate of withdrawal from cyclophosphamide treatment. The data demonstrates statistically significant improvement in one-measure of quality of life in one trial favouring cyclophosphamide over placebo and clinically and statistically significant improvement in breathlessness in one trial favouring cyclophosphamide compared with placebo, with no significant impact on mortality.Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months (FVC % MD -0.82, 95% CI -3.95 to 2.31; P = 0.61; two trials, 149 participants; DLCO % MD -1.41, 95% CI -10.40 to 7.58; P = 0.76; two trials, 149 participants).Risk of side effects was increased with cyclophosphamide versus mycophenolate, in particular, leukopenia and thrombocytopenia.The data demonstrates no significant impact on health-related quality of life, all-cause mortality, dyspnoea, or cough severity in the cyclophosphamide group compared with the mycophenolate group. No trials reported outcomes associated with functional exercise tests.We performed subgroup analysis to determine whether severity of lung function, connective tissue disease diagnosis, or radiological pattern had any impact on outcomes. One trial reported that cyclophosphamide protected against decreased FVC in individuals with worse fibrosis scores, and also showed that cyclophosphamide may be more effective in those with worse lung function. No association could be made between connective tissue disease diagnosis and outcomes. This review, which is based on studies of varying methodological quality, demonstrates that overall, in this population, small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo, but not of the difference in % DLCO, or when compared with mycophenolate. Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide. Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC. Clinicians should carefully monitor for adverse effects during treatment and in the years thereafter.Further studies are required to examine the use of cyclophosphamide; they should be adequately powered to compare outcomes within different subgroups, specifically, stratified for extent of pulmonary infiltrates on high-resolution computed tomography (HRCT) and skin involvement in SSc. Studies on other forms of connective tissue disease are needed. Researchers may consider comparing cyclophosphamide (a potent immunosuppressant) versus antifibrotic agents, or comparing both versus placebo, in particular, for those with evidence of rapidly progressive fibrotic disease, who may benefit the most.

Noninvasive Tissue Characterization of Lung Tumors Using Integrated Backscatter Intravascular Ultrasound: An Ex Vivo Comparative Study With Pathological Diagnosis.

PubMed

Ito, Fumitaka; Kawasaki, Masanori; Ohno, Yasushi; Toyoshi, Sayaka; Morishita, Megumi; Kaito, Daizo; Yanase, Komei; Funaguchi, Norihiko; Asano, Masahiro; Endo, Junki; Mori, Hidenori; Kobayashi, Kazuhiro; Nishigaki, Kazuhiko; Miyazaki, Tatsuhiko; Takemura, Genzou; Minatoguchi, Shinya

2016-05-01

Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses. Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson's trichrome staining were determined by using an imaging processor. The IBS values in tumor tissue were significantly lower than those in normal lung tissue (-50.9 ± 2.6 dB and -47.6 ± 2.6 dB, respectively; P < .001). The IBS values of adenocarcinomas associated with a good 5-year survival rate were higher than those of non-adenocarcinomas (-48.1 ± 1.6 dB and -52.6 ± 1.4 dB; P < .001). There were significant correlations between the IBS values and the relative interstitial area or micro air area in tumor (r = 0.53 and r = 0.67; P < .01). After combining normal lung tissue and adenocarcinomas with a good prognosis, the sensitivity and specificity for establishing the presence of lung tumors were 84% and 85%. Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density

DTIC Science & Technology

2005-06-01

remodelling. J Biomech, 20:1083-1093. 2. Hillsley MV, and Frangos , JA 1994 Bone tissue engineering: the role of interstitial fluid flow. Biotech Bioeng, 43...However, the nature of interaction between other pathways remains to be determined. References: 1. Hillsley MV, and Frangos , JA (1994) Bone tissue...termination 2. Hillsley, M. V., and Frangos , J. A. (1994) Biotechnol. Bioeng. 43, 573-581 of the IGF-I signaling pathway (16-22). Accordingly, we pos- 3. Kapur

Image-based diagnostic aid for interstitial lung disease with secondary data integration

NASA Astrophysics Data System (ADS)

Depeursinge, Adrien; Müller, Henning; Hidki, Asmâa; Poletti, Pierre-Alexandre; Platon, Alexandra; Geissbuhler, Antoine

2007-03-01

Interstitial lung diseases (ILDs) are a relatively heterogeneous group of around 150 illnesses with often very unspecific symptoms. The most complete imaging method for the characterisation of ILDs is the high-resolution computed tomography (HRCT) of the chest but a correct interpretation of these images is difficult even for specialists as many diseases are rare and thus little experience exists. Moreover, interpreting HRCT images requires knowledge of the context defined by clinical data of the studied case. A computerised diagnostic aid tool based on HRCT images with associated medical data to retrieve similar cases of ILDs from a dedicated database can bring quick and precious information for example for emergency radiologists. The experience from a pilot project highlighted the need for detailed database containing high-quality annotations in addition to clinical data. The state of the art is studied to identify requirements for image-based diagnostic aid for interstitial lung disease with secondary data integration. The data acquisition steps are detailed. The selection of the most relevant clinical parameters is done in collaboration with lung specialists from current literature, along with knowledge bases of computer-based diagnostic decision support systems. In order to perform high-quality annotations of the interstitial lung tissue in the HRCT images an annotation software and its own file format is implemented for DICOM images. A multimedia database is implemented to store ILD cases with clinical data and annotated image series. Cases from the University & University Hospitals of Geneva (HUG) are retrospectively and prospectively collected to populate the database. Currently, 59 cases with certified diagnosis and their clinical parameters are stored in the database as well as 254 image series of which 26 have their regions of interest annotated. The available data was used to test primary visual features for the classification of lung tissue patterns. These features show good discriminative properties for the separation of five classes of visual observations.

Novel actions of tissue-type plasminogen activator in chronic kidney disease: a paradigm shift

PubMed Central

Hu, Kebin; Mars, Wendy M.; Liu, Youhua

2009-01-01

Tissue-type plasminogen activator (tPA) is traditionally viewed as a simple serine protease whose main function is to convert plasminogen into biologically active plasmin. As a protease, tPA plays a crucial role in regulating blood fibrinolysis, in maintaining the homeostasis of extracellular matrix (ECM) and in modulating the post-translational activation of growth factors. However, emerging evidence indicates that tPA may also function as a cytokine that transmits its signal across the cell membrane, initiates a diverse array of intracellular signaling, and dictates gene expression in the nuclei. Structurally, tPA is a kringle-containing protein that shares significant similarity to other classic cytokines such as hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP). Although there is no dedicated receptor, tPA binds to the cell membrane low density lipoprotein (LDL) receptor-related protein-1 (LRP-1), triggers LRP-1 tyrosine phosphorylation, and activates various intracellular signaling. As a cytokine, tPA plays a pivotal role in the pathogenesis of renal interstitial fibrosis through diverse mechanisms. It induces matrix matelloproteinase-9 (MMP-9) gene expression in renal interstitial fibroblasts, which causes the destruction of the tubular basement membrane (TBM), thereby facilitating tubular epithelial to mesenchymal transition (EMT). tPA also potentiates myofibroblast activation from quiescent interstitial fibroblasts through LRP-1-mediated recruitment of β1 integrin signaling. Furthermore, tPA acts as a survival factor that protects renal interstitial fibroblasts/myofibroblasts from apoptosis, thereby resulting in an expansion of myofibroblast populations in diseased kidney. Together, a growing body of evidence has implicated tPA as a fibrogenic cytokine that promotes the progression of kidney diseases. These new findings have radically changed our conception of tPA in renal fibrogenesis and represent a paradigm shift towards uncovering its cytokine function. A better understanding of renal tPA biology will ultimately translate into more rational therapeutic remedies for patients with chronic kidney fibrosis. PMID:18508579

Hydrodynamically-driven drug release during interstitial flow through hollow fibers implanted near lymphatics

PubMed Central

Dukhin, Stanislav S.; Labib, Mohamed E.

2016-01-01

Current drug delivery devices (DDD) are mainly based on the use of diffusion as the main transport process. Diffusion-driven processes can only achieve low release rate because diffusion is a slow process. This represents a serious obstacle in the realization of recent successes in the suppression of lymphatic metastasis and in the prevention of limb and organ transplant rejection. Surprisingly, it was overlooked that there is a more favorable drug release mode which can be achieved when a special DDD is implanted near lymphatics. This opportunity can be realized when the interstitial fluid flow penetrates a drug delivery device of proper design and allows such fluid to flow out of it. This design is based on hollow fibers loaded with drug and whose hydrodynamic permeability is much higher than that of the surrounding tissue. The latter is referred to as hollow fiber of high hydrodynamic permeability (HFHP). The interstitial flow easily penetrates the hollow fiber membrane as well as its lumen with a higher velocity than that in the adjacent tissue. The interstitial liquid stream entering the lumen becomes almost saturated with drug as it flows out of the HFHP. This is due to the drug powder dissolution in the lumens of HFHP which forms a strip of drug solution that crosses the interstitium and finally enters the lymphatics. This hydrodynamically-driven release (HDR) may exceed the concomitant diffusion-driven release (DDR) by one or even two orders of magnitude. The hydrodynamics of the two-compartment media is sufficient for developing the HDR theory which is detailed in this paper. Convective diffusion theory for two compartments (membrane of hollow fiber and adjacent tissue) is required for exact quantification when a small contribution of DDR to predominating HDR is present. Hence, modeling is important for HDR which would lead to establishing a new branch in physico-chemical hydrodynamics. The release rate achieved with the use of HFHP increases proportional to the number of hollow fibers in the fabric employed in drug delivery. Based on this contribution, it is now possible to simultaneously provide high release rates and long release durations, thus overcoming a fundamental limitation in drug delivery. Perhaps this breakthrough in long-term drug delivery has potential applications in targeting lymphatics and in treating cancer and cancer metastasis without causing the serious side effects of systemic drugs. PMID:28579697

Endothelial necrosis at 1h post-burn predicts progression of tissue injury

PubMed Central

Hirth, Douglas; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.

2013-01-01

Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by High Mobility Group Box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1h, 24h and 7 days post-burn. Level of endothelial cell necrosis at 1h was predictive of level of apoptosis at 24h (Pearson's r=0.87) and of level of tissue necrosis at 7 days (Pearson's r=0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1h (p<0.001). Endothelial cell necrosis at 1h divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1h that progressed to necrosis by 24h, and a lower zone with initially viable endothelial cells at 1h, but necrosis and apoptosis of all cell types by 24h. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke, and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death, in burn progression. PMID:23627744

Preclinical studies of vascular acting photosensitizer bacteriopheophorbide for the treatment of prostate cancer

NASA Astrophysics Data System (ADS)

Hetzel, Fred W.; Chen, Qun; Luck, David; Beckers, Jill; Huang, Zheng

2004-06-01

Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the IV infused photosensitizer drug. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week post PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Prostate lesions could be detected by MRI scan as early as 48 h post PDT. Maximum lesion size of 1.5 cm3 and 2.9 cm3 could be achieved at 50 J/cm and 100 J/cm, respectively, with interstitial treatment using a single 1-cm diffuser fiber, suggesting the Tookad-PDT is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat localized prostate cancer.

Structure-mechanics relationships in mineralized tendons.

PubMed

Spiesz, Ewa M; Zysset, Philippe K

2015-12-01

In this paper, we review the hierarchical structure and the resulting elastic properties of mineralized tendons as obtained by various multiscale experimental and computational methods spanning from nano- to macroscale. The mechanical properties of mineralized collagen fibres are important to understand the mechanics of hard tissues constituted by complex arrangements of these fibres, like in human lamellar bone. The uniaxial mineralized collagen fibre array naturally occurring in avian tendons is a well studied model tissue for investigating various stages of tissue mineralization and the corresponding elastic properties. Some avian tendons mineralize with maturation, which results in a graded structure containing two zones of distinct morphology, circumferential and interstitial. These zones exhibit different amounts of mineral, collagen, pores and a different mineral distribution between collagen fibrillar and extrafibrillar space that lead to distinct elastic properties. Mineralized tendon cells have two phenotypes: elongated tenocytes placed between fibres in the circumferential zone and cuboidal cells with lower aspect ratios in the interstitial zone. Interestingly some regions of avian tendons seem to be predestined to mineralization, which is exhibited as specific collagen cross-linking patterns as well as distribution of minor tendon constituents (like proteoglycans) and loss of collagen crimp. Results of investigations in naturally mineralizing avian tendons may be useful in understanding the pathological mineralization occurring in some human tendons. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vivo sampling of Verteporfin uptake in pancreas cancer xenograft models: comparison of surface, oral, and interstitial measurements

NASA Astrophysics Data System (ADS)

Isabelle, Martin; O'Hara, Julia A.; Samkoe, Kimberley S.; Hoopes, P. Jack; Mosse, Sandy; Pereira, Stephen; Hasan, Tayyaba; Pogue, Brian W.

2010-02-01

Photodynamic therapy (PDT) mediated with Verteporfin is being investigated as a pancreatic cancer treatment in the cases for non-surgical candidates. Tissue response to PDT is based on a number of parameters including photosensitizer (PS) dose, light dose and time interval between light application and PS injection. In this study, PS uptake and distribution in animal leg muscle, oral cavity tissues, pancreas and tumor was measured in vivo using light-induced fluorescence spectroscopy (LIFS) via an Aurora Optics Inc. PDT fluorescence dosimeter. An orthotopic pancreatic cancer model (AsPC-1) was implanted in SCID mice and treated with the PS. Probe measurements were made using a surface probe and an interstitial needle probe before and up to one hour after intravenous tail vein injection of the PS. The study demonstrated that it is possible to correlate in-vivo LIFS measurements of the PS uptake in the pancreas with measurements taken from the oral cavity indicating that light dosimetry of PDT of the pancreas can be ascertained from the LIFS measurements in the oral cavity. These results emphasize the importance of light dosimetry in improving the therapeutic outcome of PDT through light dose adaptation to the relative in situ tissue PS concentration.

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

NASA Technical Reports Server (NTRS)

Verbanck, S.; Larsson, H.; Linnarsson, D.; Prisk, G. K.; West, J. B.; Paiva, M.

1997-01-01

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Hierarchical poroelasticity: movement of interstitial fluid between porosity levels in bones.

PubMed

Cowin, Stephen C; Gailani, Gaffar; Benalla, Mohammed

2009-09-13

The governing equations for the theory of poroelastic materials with hierarchical pore space architecture and compressible constituents undergoing small deformations are developed. These equations are applied to the problem of determining the exchange of pore fluid between the vascular porosity (PV) and the lacunar-canalicular porosity (PLC) in bone tissue due to cyclic mechanical loading and blood pressure oscillations. The result is basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. A formula for the volume of fluid that moves between the PLC and PV in a cyclic loading is obtained as a function of the cyclic mechanical loading and blood pressure oscillations. Formulas for the oscillating fluid pore pressure in both the PLC and the PV are obtained as functions of the two driving forces, the cyclic mechanical straining and the blood pressure, both with specified amplitude and frequency. The results of this study also suggest a PV permeability greater than 10(-9) m(2) and perhaps a little lower than 10(-8) m(2). Previous estimates of this permeability have been as small as 10(-14) m(2).

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy.

PubMed

Trnková, Petra; Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2010-12-01

The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning.

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy

PubMed Central

Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2011-01-01

Purpose The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. Material and methods For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. Results HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. Conclusions HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning. PMID:27853479

Inhibition mechanism of compound ethanol extracts from wuweizi (fructus schisandrae chinensis) on renal interstitial fibrosis in diabetic nephropathy model mice.

PubMed

Zhang, Yanqiu; Zhang, Daning; Zhang, Mianzhi

2012-12-01

To evaluate inhibition effect and mechanism of compound ethanol extracts from Wuweizi (Fructus Schisandrae Chinensis), Chuanxiong (Rhizoma Chuanxiong) and Muli (Cocha Ostreae) (FRC) on glomerular and tubular interstitial fibrosis in streptozocin (STZ)-induced diabetic nephropathy (ND) model mice. Twenty-seven male C57BL/6 mice were divided randomly into 3 groups: nondibetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic that were treated with 5 g x kg(-1) x day(-1) of FRC by oral gavage (D(FRC)), with 9 in each group. The protein expressions of E-cadherin, alpha-smooth muscle actin (alpha-SMA), Plasminogen Activator Inhibitor-1 (PAL-1) in renal tissues were investigated by Western blotting. The expressions of fibronectin (FN) and alpha-SMA were detected by immunohistochemical method. The morphological changes of renal tissues were observed under a microscope. Renal tissues in the D(FRC) group showed a lessened degree of fibrosis. Meanwhile, the expressions of FN, alpha-SMA and PAI-1 were significantly lower in the D(FRC) group than those in the D group (all P < 0.05). FRC can ameliorate the DN in the C57BL/6 mice, and its mechanism may relate to inhibition on the epithelial to mesenchymal transdifferentiation, endothelial-myofibroblast transition and PAL-1 expression.

3D Proximal Tubule Tissues Recapitulate Key Aspects of Renal Physiology to Enable Nephrotoxicity Testing

PubMed Central

King, Shelby M.; Higgins, J. William; Nino, Celina R.; Smith, Timothy R.; Paffenroth, Elizabeth H.; Fairbairn, Casey E.; Docuyanan, Abigail; Shah, Vishal D.; Chen, Alice E.; Presnell, Sharon C.; Nguyen, Deborah G.

2017-01-01

Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited in vitro functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human in vitro model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes. Histological characterization demonstrated formation of extensive microvascular networks supported by endogenous extracellular matrix deposition. The epithelial cells of the 3D proximal tubule tissues demonstrated tight junction formation and expression of renal uptake and efflux transporters; the polarized localization and function of P-gp and SGLT2 were confirmed. Treatment of 3D proximal tubule tissues with the nephrotoxin cisplatin induced loss of tissue viability and epithelial cells in a dose-dependent fashion, and cimetidine rescued these effects, confirming the role of the OCT2 transporter in cisplatin-induced nephrotoxicity. The tissues also demonstrated a fibrotic response to TGFβ as assessed by an increase in gene expression associated with human fibrosis and histological verification of excess extracellular matrix deposition. Together, these results suggest that the bioprinted 3D proximal tubule model can serve as a test bed for the mechanistic assessment of human nephrotoxicity and the development of pathogenic states involving epithelial-interstitial interactions, making them an important adjunct to animal studies. PMID:28337147

An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

NASA Technical Reports Server (NTRS)

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, media] gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

Increased Lymphatic Vessel Length Is Associated With the Fibroblast Reticulum and Disease Severity in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

PubMed Central

Cosgrove, Gregory P.; Janssen, William J.; Huie, Tristan J.; Burnham, Ellen L.; Heinz, David E.; Curran-Everett, Douglas; Sahin, Hakan; Schwarz, Marvin I.; Cool, Carlyne D.; Groshong, Steve D.; Geraci, Mark W.; Tuder, Rubin M.; Hyde, Dallas M.; Henson, Peter M.

2012-01-01

Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC < 80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density (P < .0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC (P < .001) and diffusing capacity of the lung for carbon monoxide (P < .001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases. PMID:22797508

Interstitial flow influences direction of tumor cell migration through competing mechanisms

PubMed Central

Polacheck, William J.; Charest, Joseph L.; Kamm, Roger D.

2011-01-01

Interstitial flow is the convective transport of fluid through tissue extracellular matrix. This creeping fluid flow has been shown to affect the morphology and migration of cells such as fibroblasts, cancer cells, endothelial cells, and mesenchymal stem cells. A microfluidic cell culture system was designed to apply stable pressure gradients and fluid flow and allow direct visualization of transient responses of cells seeded in a 3D collagen type I scaffold. We used this system to examine the effects of interstitial flow on cancer cell morphology and migration and to extend previous studies showing that interstitial flow increases the metastatic potential of MDA-MB-435S melanoma cells [Shields J, et al. (2007) Cancer Cell 11:526–538]. Using a breast carcinoma line (MDA-MB-231) we also observed cell migration along streamlines in the presence of flow; however, we further demonstrated that the strength of the flow as well as the cell density determined directional bias of migration along the streamline. In particular, we found that cells either at high seeding density or with the CCR-7 receptor inhibited migration against, rather than with the flow. We provide further evidence that CCR7-dependent autologous chemotaxis is the mechanism that leads to migration with the flow, but also demonstrate a competing CCR7-independent mechanism that causes migration against the flow. Data from experiments investigating the effects of cell concentration, interstitial flow rate, receptor activity, and focal adhesion kinase phosphorylation support our hypothesis that the competing stimulus is integrin mediated. This mechanism may play an important role in development of metastatic disease. PMID:21690404

Coagulative interstitial laser-induced thermotherapy of benign prostatic hyperplasia: online imaging with a T2-weighted fast spin-echo MR sequence--experience in six patients.

PubMed

Mueller-Lisse, U G; Thoma, M; Faber, S; Heuck, A F; Muschter, R; Schneede, P; Weninger, E; Hofstetter, A G; Reiser, M F

1999-02-01

To determine if hypointense lesions clearly outline on T2-weighted fast spin-echo (SE) magnetic resonance (MR) images obtained during coagulative interstitial laser-induced thermotherapy (LITT) of a prostate with benign hyperplasia. In six patients with benign prostatic hyperplasia (BPH), 12 LITT treatments were followed online with repetitive axial T2-weighted fast SE imaging (repetition time, 3,700 msec; echo time, 138 msec; acquisition time, 19 seconds). Development, time course, correlation with interstitial tissue temperature, and diameters of hypointense lesions around the laser diffusor tip were investigated. Lesion diameters on T2-weighted images acquired during LITT were compared with diameters of final lesions on T2-weighted images and unperfused lesions on enhanced T1-weighted SE images obtained at the end of therapy. Hypointense lesions developed within 20-40 seconds of LITT. Average correlation coefficients between interstitial temperature development and signal intensity development were 0.92 during LITT and 0.90 after LITT. Regression slopes were significantly steeper during LITT (0.67% signal intensity change per degree Celsius) than after LITT (0.47% per degree Celsius; P = .038). Lesions remained visible after LITT for all procedures. Average maximum diameters of lesions were 1-3 mm larger during LITT than after LITT (P = .0006-.019). Repetitive T2-weighted fast SE MR imaging during interstitial coagulative LITT of BPH demonstrates the development of permanent hypointense prostate lesions. However, posttherapeutic lesion diameters tend to be overestimated during LITT.

3-compartment talaporfin sodium pharmacokinetic model by optimization using fluorescence measurement data from canine skin to estimate the concentration in interstitial space

NASA Astrophysics Data System (ADS)

Uno, Yuko; Ogawa, Emiyu; Aiyoshi, Eitaro; Arai, Tsunenori

2018-02-01

We constructed the 3-compartment talaporfin sodium pharmacokinetic model for canine by an optimization using the fluorescence measurement data from canine skin to estimate the concentration in the interstitial space. It is difficult to construct the 3-compartment model consisted of plasma, interstitial space, and cell because there is a lack of the dynamic information. Therefore, we proposed the methodology to construct the 3-compartment model using the measured talaporfin sodium skin fluorescence change considering originated tissue part by a histological observation. In a canine animal experiment, the talaporfin sodium concentration time history in plasma was measured by a spectrophotometer with a prepared calibration curve. The time history of talaporfin sodium Q-band fluorescence on left femoral skin of a beagle dog excited by talaporfin sodium Soret-band of 409 nm was measured in vivo by our previously constructed measurement system. The measured skin fluorescence was classified to its source, that is, specific ratio of plasma, interstitial space, and cell. We represented differential rate equations of the talaporfin sodium concentration in plasma, interstitial space, cell. The specific ratios and a converting constant to obtain absolute value of skin concentration were arranged. Minimizing the squared error of the difference between the measured fluorescence data and calculated concentration by the conjugate gradient method in MATLAB, the rate constants in the 3-compartment model were determined. The accuracy of the fitting operation was confirmed with determination coefficient of 0.98. We could construct the 3-compartment pharmacokinetic model for canine using the measured talaporfin sodium fluorescence change from canine skin.

A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy.

PubMed

Freund, Jonathan B; Colonius, Tim; Evan, Andrew P

2007-09-01

Evidence suggests that inertial cavitation plays an important role in the renal injury incurred during shock-wave lithotripsy. However, it is unclear how tissue damage is initiated, and significant injury typically occurs only after a sufficient dose of shock waves. Although it has been suggested that shock-induced shearing might initiate injury, estimates indicate that individual shocks do not produce sufficient shear to do so. In this paper, we hypothesize that the cumulative shear of the many shocks is damaging. This mechanism depends on whether there is sufficient time between shocks for tissue to relax to its unstrained state. We investigate the mechanism with a physics-based simulation model, wherein the basement membranes that define the tubules and vessels in the inner medulla are represented as elastic shells surrounded by viscous fluid. Material properties are estimated from in-vitro tests of renal basement membranes and documented mechanical properties of cells and extracellular gels. Estimates for the net shear deformation from a typical lithotripter shock (approximately 0.1%) are found from a separate dynamic shock simulation. The results suggest that the larger interstitial volume (approximately 40%) near the papilla tip gives the tissue there a relaxation time comparable to clinical shock delivery rates (approximately 1 Hz), thus allowing shear to accumulate. Away from the papilla tip, where the interstitial volume is smaller (approximately 20%), the model tissue relaxes completely before the next shock would be delivered. Implications of the model are that slower delivery rates and broader focal zones should both decrease injury, consistent with some recent observations.

A Novel Esthetic Approach using Connective Tissue Graft for Soft Tissue Defect Following Surgical Excision of Gingival Fibrolipoma

PubMed Central

Parthasarathy, Harinath; Kumar, Praveenkrishna; Gajendran, Priyalochana; Appukuttan, Devapriya

2014-01-01

The aim of the present case report is to evaluate the adjunctive use of a connective tissue graft to overcome soft tissue defects following excision of a gingival fibrolipoma in the aesthetic region. Connective tissue graft has been well documented for treating defects of esthetic concern. However, the literature does not contain many reports on the esthetic clinical outcome following the use of connective tissue graft secondary to excision of soft tissue tumours. A 28-year-old male patient reported with a complaint of a recurrent growth in relation to his lower front tooth region. The lesion which was provisionally diagnosed as fibroma was treated with a complete surgical excision, following which a modified coronally advanced flap and connective tissue graft was adopted to overcome the soft tissue defect. The excised growth was diagnosed histologically as fibrolipoma. One year follow up showed no recurrence of the lesion and good esthetics.The adjunctive use of the connective tissue graft and modified coronally advanced flap predictably yields optimal soft tissue fill and excellent esthetics. Hence, routine use of this procedure may be recommended for surgical excision of soft tissue growths in esthetically sensitive areas. PMID:25584336

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

PubMed

Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

2017-01-01

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

[Oral rehabilitation with metalloceramic restorations in patients with non-differentiated systemic connective tissue dysplasia].

PubMed

Stafeev, А А

2015-01-01

False formation of connective tissues have a great influence on structure and function of organs and tissues of the human body. In prosthodontics, the changes in connective tissues greatly occur during clinical stages of preparing metal ceramic dentures. The algorithm of treatment patients with connective tissue dysplasia during metal ceramic dentures was developed and introduced into practical dentistry based on studying the morphology and functionality of dentition and clinical experience.

A characterization of the coupled evolution of grain fabric and pore space using complex networks: Pore connectivity and optimized flows in the presence of shear bands

NASA Astrophysics Data System (ADS)

Russell, Scott; Walker, David M.; Tordesillas, Antoinette

2016-03-01

A framework for the multiscale characterization of the coupled evolution of the solid grain fabric and its associated pore space in dense granular media is developed. In this framework, a pseudo-dual graph transformation of the grain contact network produces a graph of pores which can be readily interpreted as a pore space network. Survivability, a new metric succinctly summarizing the connectivity of the solid grain and pore space networks, measures material robustness. The size distribution and the connectivity of pores can be characterized quantitatively through various network properties. Assortativity characterizes the pore space with respect to the parity of the number of particles enclosing the pore. Multiscale clusters of odd parity versus even parity contact cycles alternate spatially along the shear band: these represent, respectively, local jamming and unjamming regions that continually switch positions in time throughout the failure regime. Optimal paths, established using network shortest paths in favor of large pores, provide clues on preferential paths for interstitial matter transport. In systems with higher rolling resistance at contacts, less tortuous shortest paths thread through larger pores in shear bands. Notably the structural patterns uncovered in the pore space suggest that more robust models of interstitial pore flow through deforming granular systems require a proper consideration of the evolution of in situ shear band and fracture patterns - not just globally, but also inside these localized failure zones.

Qualitative assessment of connective tissue graft with epithelial component. A microsurgical periodontal plastic surgical technique for soft tissue esthetics.

PubMed

Rossi, Roberto; Pilloni, Andrea; Morales, Regina Santos

2009-01-01

Connective tissue grafts have been used successfully in the treatment of gingival recession. In the mid 80s and late 90s, the periodontal literature presented various techniques such as free gingival grafts, pedicle flaps, subepithelial connective tissue grafts, acellular dermal matrix grafts, and guided tissue regeneration to cover denuded root surfaces. Currently, connective tissue grafting is a reliable treatment for esthetic root coverage. This paper presents a qualitative assessment of a surgical technique that uses a connective tissue graft, including a portion of epithelium in the shape of the defect. This procedure enhances the healing of the covered root surface, increases the thickness of the soft tissue and improves esthetics. The criteria used for evaluation were: color, volume, texture, and blending. This evaluation demonstrated encouraging results from an esthetic viewpoint.

Polycystic kidney disease in a European roe deer (Capreolus capreolus).

PubMed

Blutke, Andreas; März, Kristian; Matenaers, Cyrill; Oswald, Karl; Hermanns, Walter; Wanke, Rüdiger

2013-06-01

A severe case of polycystic nephropathy was seen in an adult European roe deer (Capreolus capreolus), culled in a German hunting district. The doe had bilaterally drastically enlarged kidneys, completely riddled with variably sized, fluid-filled cysts of up to 4 cm in diameter. Histopathologic and ultrastructural examination revealed disseminated formation of cysts with flattened epithelial cell linings in the entire renal parenchyma, as well as severe dilations of renal tubules, marked interstitial fibrosis, nephron atrophy, and chronic interstitial lymphoplasmacytic infiltrations in the intercystic kidney tissue. These morphologic findings most likely resemble the hallmarks of autosomal dominant polycystic disease in humans, and present the first detailed description of a case of polycystic kidney disease in a roe deer.

SU-E-J-04: Integration of Interstitial High Intensity Therapeutic Ultrasound Applicators On a Clinical MRI-Guided High Intensity Focused Ultrasound Treatment Planning Software Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellens, N; Partanen, A; Ghoshal, G

Purpose: Interstitial high intensity therapeutic ultrasound (HITU) applicators can be used to ablate tissue percutaneously, allowing for minimally-invasive treatment without ionizing radiation [1,2]. The purpose of this study was to evaluate the feasibility and usability of combining multielement interstitial HITU applicators with a clinical magnetic resonance imaging (MRI)-guided focused ultrasound software platform. Methods: The Sonalleve software platform (Philips Healthcare, Vantaa, Finland) combines anatomical MRI for target selection and multi-planar MRI thermometry to provide real-time temperature information. The MRI-compatible interstitial US applicators (Acoustic MedSystems, Savoy, IL, USA) had 1–4 cylindrical US elements, each 1 cm long with either 180° or 360°more » of active surface. Each applicator (4 Fr diameter, enclosed within a 13 Fr flexible catheter) was inserted into a tissue-mimicking agar-silica phantom. Degassed water was circulated around the transducers for cooling and coupling. Based on the location of the applicator, a virtual transducer overlay was added to the software to assist targeting and to allow automatic thermometry slice placement. The phantom was sonicated at 7 MHz for 5 minutes with 6–8 W of acoustic power for each element. MR thermometry data were collected during and after sonication. Results: Preliminary testing indicated that the applicator location could be identified in the planning images and the transducer locations predicted within 1 mm accuracy using the overlay. Ablation zones (thermal dose ≥ 240 CEM43) for 2 active, adjacent US elements ranged from 18 mm × 24 mm (width × length) to 25 mm × 25 mm for the 6 W and 8 W sonications, respectively. Conclusion: The combination of interstitial HITU applicators and this software platform holds promise for novel approaches in minimally-invasive MRI-guided therapy, especially when bony structures or air-filled cavities may preclude extracorporeal HIFU.[1] Diederich et al. IEEE UFFFC 46.5 (1999): 1218.[2] Chopra et al. PMB 50.21 (2005): 4957. Funding support was provided by Philips Healthcare and in-kind support from Acoustic MedSystems Inc. Ari Partanen is a paid employee of Philips Healthcare. Goutam Ghoshal and Everette Clif Burdette are paid employees of Acoustic MedSystems Inc.« less

Effects of TOOKAD-PDT on canine prostates pre-treated with ionizing radiation

NASA Astrophysics Data System (ADS)

Chen, Qun; Huang, Zheng; Luck, David L.; Beckers, Jill; Trncic, Nadira; LaRue, Susan M.; Brun, Pierre-Herve; Wilson, Brian C.; Hetzel, Fred W.

2003-06-01

PDT in prostate cancer will likely be implemented clinically with patients who have failed prior ionizing radiation therapy (RT). The current study is to develop an in vivo model to evaluate the effects of PDT on prostatic tissue after RT. To produce a physiological and anatomical environment in prostate similar to that in patients who have failed RT, canine prostates (n=4) were subjected to a definitive course of ionizing radiation therapy (2.7 Gy x 20 fractions) 5 to 6 months prior to PDT. A laparotomy was performed to expose the prostate for PDT. Second generation photosensitizer Tookad (Palladium-Bacteriopheophorbide, Steba Biotech, The Netherlands) acts primarily on tissue vasculature and is very effective in destroying normal prostatic tissue, as shown by our prior studies. Due to the extremely fast clearance of the photosensitizer, interstitial light irradiation (760 nm, 50-200 J/cm, 150 mW/cm from a 1 cm diffuser fiber) was delivered 4 minutes after the onset of Tookad infusion (i.v. 2.5 mg/ml, 2 mg/kg, total infusion time 10 min). The prostates were harvested for histopathology one week after PDT. At one week, the lesions were characterized by acute hemorrhagic necrosis with patchy sub-capsular hyperemia and edema. The maximum lesion diameter for 50, 100 and 200 J/cm PDT was approximately 15, 20 and 28 mm, respectively. The lesion size is well correlated with light fluence and comparable to that in prostates treated with identical PDT doses but without prior-RT. Under light-microscopy, the PDT induced necrosis is clearly distinguishable from the radiation induced fibrosis. No urethral lesions were observed. Dyer"s Verhoeff stain showed the loss of stromal connective tissue and the acinar collagen in the PDT treated area. There was no noticeable damage on the bladder or underlying colon section. In conclusion, Tookad-PDT can effectively destroy prostate tissue with prior-RT induced fibrosis, thus, may provide an alternative modality for those prostate-cancer patients who have failed RT.

Latest advances in edema

NASA Technical Reports Server (NTRS)

Villavicencio, J. L.; Hargens, A. R.; Pikoulicz, E.

1996-01-01

Basic concepts in the physiopathology of edema are reviewed. The mechanisms of fluid exchange across the capillary endothelium are explained. Interstitial flow and lymph formation are examined. Clinical disorders of tissue and lymphatic transport, microcirculatory derangements in venous disorders, protein disorders, and lymphatic system disorders are explored. Techniques for investigational imaging of the lymphatic system are explained.

Scleroderma

MedlinePlus

... of diseases that cause abnormal growth of connective tissue. Connective tissue is the material inside your body that gives ... joints. Symptoms of scleroderma include Calcium deposits in connective tissues Raynaud's phenomenon, a narrowing of blood vessels in ...

Sonic hedgehog signaling in kidney fibrosis: a master communicator.

PubMed

Zhou, Dong; Tan, Roderick J; Liu, Youhua

2016-09-01

The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial- mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients.

Sonic hedgehog signaling in kidney fibrosis: a master communicator

PubMed Central

Zhou, Dong; Tan, Roderick J.; Liu, Youhua

2017-01-01

The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial-mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients. PMID:27333788

Lesions of neonatally induced toxoplasmosis in cats.

PubMed

Dubey, J P; Mattix, M E; Lipscomb, T P

1996-05-01

Five pregnant queens were inoculated orally with Toxoplasma gondii tissue cysts. Twenty-two live and three dead kittens were born 16 to 31 days after inoculation. Four kittens were eaten by queens and, thus, were not available for histologic examination. Twenty-one kittens that died or were euthanatized on day 2 (two kittens), 4 (one kitten), 5 (five kittens), 6 (five kittens), 7 (one kitten), 8 (four kittens), 16 (two kittens), and 29 (one kitten) after birth were studied histologically. T gondii was detected by bioassay and was seen in histologic sections of tissues from all 21 kittens. The histologic lesions associated with neonatal toxoplasmosis were widely disseminated infiltrates of macrophages and neutrophils often accompanied by necrosis; lymphocytes and plasma cells were occasionally present. The most consistent lesions were proliferative interstitial pneumonia (21/21); necrotizing hepatitis (20/21); myocarditis (21/21); skeletal myositis (21/21); glossal myositis (19/19); nonsuppurative encephalitis affecting the cerebrum (18/18), brain stem (15/15), and spinal cord (9/9); uveitis (19/19); necrotizing adrenal adenitis (18/18); and interstitial nephritis (16/21). Placental lesions (2/2) consisted of grossly visible areas of necrosis and mineralization.

Blood Flow Changes in Subsynovial Connective Tissue on Contrast-Enhanced Ultrasonography in Patients With Carpal Tunnel Syndrome Before and After Surgical Decompression.

PubMed

Motomiya, Makoto; Funakoshi, Tadanao; Ishizaka, Kinya; Nishida, Mutsumi; Matsui, Yuichiro; Iwasaki, Norimasa

2017-11-24

Although qualitative alteration of the subsynovial connective tissue in the carpal tunnel is considered to be one of the most important factors in the pathophysiologic mechanisms of carpal tunnel syndrome (CTS), little information is available about the microcirculation in the subsynovial connective tissue in patients with CTS. The aims of this study were to use contrast-enhanced ultrasonography (US) to evaluate blood flow in the subsynovial connective tissue proximal to the carpal tunnel in patients with CTS before and after carpal tunnel release. The study included 15 volunteers and 12 patients with CTS. The blood flow in the subsynovial connective tissue and the median nerve was evaluated preoperatively and at 1, 2, and 3 months postoperatively using contrast-enhanced US. The blood flow in the subsynovial connective tissue was higher in the patients with CTS than in the volunteers. In the patients with CTS, there was a significant correlation between the blood flow in the subsynovial connective tissue and the median nerve (P = .01). The blood flow in both the subsynovial connective tissue and the median nerve increased markedly after carpal tunnel release. Our results suggest that increased blood flow in the subsynovial connective tissue may play a role in the alteration of the microcirculation within the median nerve related to the pathophysiologic mechanisms of CTS. The increase in the blood flow in the subsynovial connective tissue during the early postoperative period may contribute to the changes in intraneural circulation, and these changes may lead to neural recovery. © 2017 by the American Institute of Ultrasound in Medicine.

Pectus Excavatum and Heritable Disorders of the Connective Tissue

PubMed Central

Tocchioni, Francesca; Ghionzoli, Marco; Messineo, Antonio; Romagnoli, Paolo

2013-01-01

Pectus excavatum, the most frequent congenital chest wall deformity, may be rarely observed as a sole deformity or as a sign of an underlying connective tissue disorder. To date, only few studies have described correlations between this deformity and heritable connective tissue disorders such as Marfan, Ehlers-Danlos, Poland, MASS (Mitral valve prolapse, not progressive Aortic enlargement, Skeletal and Skin alterations) phenotype among others. When concurring with connective tissue disorder, cardiopulmonary and vascular involvement may be associated to the thoracic defect. Ruling out the concomitance of pectus excavatum and connective tissue disorders, therefore, may have a direct implication both on surgical outcome and long term prognosis. In this review we focused on biological bases of connective tissue disorders which may be relevant to the pathogenesis of pectus excavatum, portraying surgical and clinical implication of their concurrence. PMID:24198927

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.

PubMed

Cheung, Laurence C; Strickland, Deborah H; Howlett, Meegan; Ford, Jette; Charles, Adrian K; Lyons, Karen M; Brigstock, David R; Goldschmeding, Roel; Cole, Catherine H; Alexander, Warren S; Kees, Ursula R

2014-07-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. Copyright© Ferrata Storti Foundation.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

PubMed Central

Cheung, Laurence C.; Strickland, Deborah H.; Howlett, Meegan; Ford, Jette; Charles, Adrian K.; Lyons, Karen M.; Brigstock, David R.; Goldschmeding, Roel; Cole, Catherine H.; Alexander, Warren S.; Kees, Ursula R.

2014-01-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. PMID:24727816

An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

NASA Technical Reports Server (NTRS)

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. Purpose: The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, medial gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

Bone tissue engineering: the role of interstitial fluid flow

NASA Technical Reports Server (NTRS)

Hillsley, M. V.; Frangos, J. A.

1994-01-01

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Photodynamic therapy for treatment of solid tumors – potential and technical challenges

PubMed Central

Huang, Zheng; Xu, Heping; Meyers, Arlen D.; Musani, Ali I.; Wang, Luowei; Tagg, Randall; Barqawi, Al B.; Chen, Yang K.

2008-01-01

Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors. PMID:18642969

Histopathologic lesions in sea otters exposed to crude oil

USGS Publications Warehouse

Lipscomb, T.P.; Harris, R.K.; Moeller, R.B.; Pletcher, J.M.; Haebler, R.J.; Ballachey, Brenda E.

1993-01-01

Following the Exxon Valdez oil spill in Prince William Sound, Alaska, sea otters (Enhydra lutris) that appeared to be contaminated with oil, that were in danger of becoming contaminated, or that were behaving abnormally were captured and taken to rehabilitation centers. Exposure to oil was assessed by visual examination when otters arrived at the centers. Degree of oil exposure was graded according to the following criteria: oil covering greater than 60% of the body - heavily contaminated; oil covering 30–60% of the body - moderately contaminated; oil covering less than 30% of the body or light sheen on fur - lightly contaminated. If there was no oil visible, otters were considered uncontaminated. Tissues from 51 oil-contaminated sea otters (14 males, 37 females) and from six uncontaminated sea otters (three males, three females) that died in rehabilitation centers were examined histologically. Among oil-contaminated sea otters, 19/46 had interstitial pulmonary emphysema, 13/40 had gastric erosion and hemorrhage, 11/47 had centrilobular hepatic necrosis, 14/47 had periportal to diffuse hepatic lipidosis, and 10/42 had renal tubular lipidosis. Of the uncontaminated sea otters, 1/6 had gastric erosion and hemorrhage and 1/6 had diffuse hepatic lipidosis. Histologic examinations were performed on tissues from five sea otters (three males, two females) found dead with external oil present 15 to 16 days after the spill. Periportal hepatic lipidosis and renal tubular lipidosis were found in 3/5, and interstitial pulmonary emphysema was found in 1/5. Tissues from six apparently normal sea otters (four males, two females) collected from an area not affected by an oil spill were examined histologically, and none of these lesions were found. We conclude that interstitial pulmonary emphysema, centrilobular hepatic necrosis, and hepatic and renal lipidosis of sea otters were associated with exposure to crude oil. Gastric erosion and hemorrhage may have been associated with stress of captivity and/or oil exposure.

Bladder mucosa pH and Pco2 as a minimally invasive monitor of hemorrhagic shock and resuscitation.

PubMed

Clavijo-Alvarez, Julio A; Sims, Carrie A; Menconi, Michael; Shim, Inbo; Ochoa, Christian; Puyana, Juan Carlos

2004-12-01

Continuous monitoring of pH, Pco2, and Po2 using fiberoptic sensor technology has been proposed recently as a clinical monitor of the severity of shock and impaired tissue perfusion. Surrogates of gut tissue perfusion such as gastric tonometry, although cumbersome, have been used to indirectly quantify the degree of gut ischemia. The purpose of this study was to demonstrate the feasibility of monitoring bladder mucosa (BM) and to compare urinary bladder mucosa and proximal jejunum mucosa interstitial pH and Pco2 during hemorrhagic shock and resuscitation. Eleven male miniature swine (25-35 kg) (control, n = 4; shock, n = 7) underwent jejunal tonometry and cystostomy. A multisensor probe was placed adjacent to the BM. Urine was diverted. Normocarbia was maintained. Animals were hemorrhaged and kept at a mean arterial pressure of 40 mm Hg. When a constant infusion was required to maintain the mean arterial pressure at 40 mm Hg (decompensation), animals were resuscitated with shed blood plus two times the shed volume in lactated Ringer's solution (20 minutes) and observed for 2 hours. During decompensation, BM pH values decreased significantly from 7.33 +/- 0.08 to 7.01 +/- 0.2 (p < 0.01) and recovered to 7.11 +/- 0.19 at 120 minutes after completion of resuscitation. During decompensation, BM Pco2 values increased significantly compared with baseline (from 49 +/- 6 mm Hg to 71 +/- 19 mm Hg, p < 0.05) and returned to baseline with resuscitation. Jejunum mucosa and BM interstitial Pco2 correlated throughout shock and resuscitation (r = 0.49). Bland-Altman analysis demonstrated significant differences between jejunum mucosa (intramucosal pH) and BM interstitial pH. Shock-induced changes in the Pco2 of the BM are comparable to tonometric changes in the gut. These data suggest that continuous fiberoptic multisensor probe monitoring of the BM could potentially provide a minimally invasive method for the assessment of impaired tissue perfusion of the splanchnic circulation during shock and resuscitation.

Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

PubMed

Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

2018-03-29

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

Physical aspects of thermotherapy: A study of heat transport with a view to treatment optimisation

NASA Astrophysics Data System (ADS)

Olsrud, Johan Karl Otto

1998-12-01

Local treatment with the aim to destruct tissue by heating (thermotherapy) may in some cases be an alternative or complement to surgical methods, and has gained increased interest during the last decade. The major advantage of these, often minimally-invasive methods, is that the disease can be controlled with reduced treatment trauma and complications. The extent of thermal damage is a complex function of the physical properties of tissue, which influence the temperature distribution, and of the biological response to heat. In this thesis, methods of obtaining a well-controlled treatment have been studied from a physical point of view, with emphasis on interstitial laser-induced heating of tumours in the liver and intracavitary heating as a treatment for menorrhagia. Hepatic inflow occlusion, in combination with temperature-feedback control of the output power of the laser, resulted in well defined damaged volumes during interstitial laser thermotherapy in normal porcine liver. In addition, phantom experiments showed that the use of multiple diffusing laser fibres allows heating of clinically relevant tissue volumes in a single session. Methods for numerical simulation of heat transport were used to calculate the temperature distribution and the results agreed well with experiments. It was also found from numerical simulation that the influence of light transport on the damaged volume may be negligible in interstitial laser thermotherapy in human liver. Finite element analysis, disregarding light transport, was therefore proposed as a suitable method for 3D treatment planning. Finite element simulation was also used to model intracavitary heating of the uterus, with the purpose of providing an increased understanding of the influence of various treatment parameters on blood flow and on the depth of tissue damage. The thermal conductivity of human uterine tissue, which was used in these simulations, was measured. Furthermore, magnetic resonance imaging (MRI) was investigated as a method of non-invasive temperature monitoring, and an optically tissue-like phantom material, suitable for MRI, was developed. MRI thermometry in this material was shown to be an excellent method for characterization of laser applicators and for verification of numerical calculations. Finally, a water-cooled laser applicator for the treatment of benign prostatic hyperplasia, allowing anatomically correct heating, was developed and evaluated ex-vivo. An increased understanding of the physical aspects of thermotherapy, aided by the methods and results presented in this thesis, constitutes a significant contribution to the performance of safe and efficacious treatment.

Early detection of acute tubulointerstitial nephritis in the genesis of Mesoamerican nephropathy.

PubMed

Fischer, Rebecca S B; Vangala, Chandan; Truong, Luan; Mandayam, Sreedhar; Chavarria, Denis; Granera Llanes, Orlando M; Fonseca Laguna, Marcos U; Guerra Baez, Alvaro; Garcia, Felix; García-Trabanino, Ramón; Murray, Kristy O

2018-03-01

Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0.3 mg/dL or 1.5-fold from baseline) serum creatinine, leukocyturia, and either leukocytosis or neutrophilia for inclusion in this biopsy study. Renal tissue was obtained by ultrasound-guided biopsy for examination by light, immunofluorescence, and electron microscopy. All 11 individuals who underwent renal biopsy showed tubulointerstitial nephritis, with varying degrees of inflammation and chronicity. Interstitial cellular infiltrates (predominantly T lymphocytes and monocytes), mostly in the corticomedullary junction; neutrophilic accumulation in the tubular lumens; largely preserved glomeruli; few mild ischemic changes; and no immune deposits were noted. The acute components of tubulointerstitial nephritis were acute tubular cell injury, interstitial edema, and early fibrosis. Chronic tubulointerstitial nephritis included severe tubular atrophy, thickened tubular basement membrane, and interstitial fibrosis. Thus, renal histopathology in Mesoamerican nephropathy reveals primary interstitial disease with intact glomeruli. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Production of Fibronectin by the Human Alveolar Macrophage: Mechanism for the Recruitment of Fibroblasts to Sites of Tissue Injury in Interstitial Lung Diseases

NASA Astrophysics Data System (ADS)

Rennard, Stephen I.; Hunninghake, Gary W.; Bitterman, Peter B.; Crystal, Ronald G.

1981-11-01

Because cells of the mononuclear phagocyte system are known to produce fibronectin and because alveolar macrophages are activated in many interstitial lung diseases, the present study was designed to evaluate a role for the alveolar macrophage as a source of the increased levels of fibronectin found in the lower respiratory tract in interstitial lung diseases and to determine if such fibronectin might contribute to the development of the fibrosis found in these disorders by being a chemoattractant for human lung fibroblasts. Production of fibronectin by human alveolar macrophages obtained by bronchoalveolar lavage and maintained in short-term culture in serum-free conditions was demonstrated; de novo synthesis was confirmed by the incorporation of [14C]proline. This fibronectin had a monomer molecular weight of 220,000 and was antigenically similar to plasma fibronectin. Macrophages from patients with idiopathic pulmonary fibrosis produced fibronectin at a rate 20 times higher than did normal macrophages; macrophages from patients with pulmonary sarcoidosis produced fibronectin at 10 times the normal rate. Macrophages from 6 of 10 patients with various other interstitial disorders produced fibronectin at rates greater than the rate of highest normal control. Human alveolar macrophage fibronectin was chemotactic for human lung fibroblasts, suggesting a functional role for this fibronectin in the derangement of the alveolar structures that is characteristic of these disorders.

Genetics Home Reference: arterial tortuosity syndrome

MedlinePlus

... tortuosity syndrome is a disorder that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the ... outside the circulatory system are caused by abnormal connective tissue in other parts of the body. These features ...

Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.

PubMed

Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

2013-04-01

We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.

Internal strains after recovery of hardness in tempered martensitic steels for fusion reactors

NASA Astrophysics Data System (ADS)

Brunelli, L.; Gondi, P.; Montanari, R.; Coppola, R.

1991-03-01

After tempering, with recovery of hardness, MANET steels present internal strains; these residual strains increase with quenching rate prior to tempering, and they remain after prolonged tempering times. On account of their persistence, after thermal treatments which lead to low dislocation and sub-boundary densities, the possibility has been considered that the high swelling resistance of MANET is connected with these centres of strain, probably connected with the formation, in ferrite, of Cr-enriched and contiguous Cr-depleted zones which may act as sinks for interstitials. Comparative observations on the internal strain behaviour of cold worked 316L stainless steel appear consistent with this possibility.

Implications of using thermocouple thermometry in 27 MHz capacitively coupled interstitial hyperthermia.

PubMed

Crezee, J; van der Koijk, J F; Kaatee, R S; Lagendijk, J J

1997-04-01

The 27 MHz Multi Electrode Current Source (MECS) interstitial hyperthermia system uses segmented electrodes, 10-20 mm long, to steer the 3D power deposition. This power control at a scale of 1-2 cm requires detailed and accurate temperature feedback data. To this end seven-point thermocouples are integrated into the probes. The aim of this work was to evaluate the feasibility and reliability of integrated thermometry in the 27 MHz MECS system, with special attention to the interference between electrode and thermometry and its effect on system performance. We investigated the impact of a seven-sensor thermocouple probe (outer diameter 150 microns) on the apparent impedance and power output of a 20 mm dual electrode (O.D. 1.5 mm) in a polyethylene catheter in a muscle equivalent medium (sigma 1 = 0.6 S m-1). The cross coupling between electrode and thermocouple was found to be small (1-2 pF) and to cause no problems in the dual-electrode mode, and only minimal problems in the single-electrode mode. Power loss into the thermometry system can be prevented using simple filters. The temperature readings are reliable and representative of the actual tissue temperature around the electrode. Self-heating effects, occurring in some catheter materials, are eliminated by sampling the temperature after a short power-off interval. We conclude that integrated thermocouple thermometry is compatible with 27 MHz capacitively coupled interstitial hyperthermia. The performance of the system is not affected and the temperatures measured are a reliable indication of the maximum tissue temperatures.

Ultrasound features of purulent skin and soft tissue infection without abscess.

PubMed

Nelson, Courtney E; Chen, Aaron E; Bellah, Richard D; Biko, David M; Ho-Fung, Victor M; Francavilla, Michael L; Xiao, Rui; Kaplan, Summer L

2018-06-06

Ultrasound (US) aids clinical management of skin and soft tissue infection (SSTI) by differentiating non-purulent cellulitis from abscess. However, purulent SSTI may be present without abscess. Guidelines recommend incision and drainage (I & D) for purulent SSTI, but US descriptions of purulent SSTI without abscess are lacking. We retrospectively reviewed pediatric emergency department patients with US of the buttock read as negative for abscess. We identified US features of SSTI with adequate interobserver agreement (kappa > 0.45). Six independent observers then ranked presence or absence of these features on US exams. We studied association between US features and positive wound culture using logistic regression models (significance at p < 0.05). Of 217 children, 35 patients (16%) had cultures positive for pathogens by 8 h after US and 61 patients (32%) had cultures positive by 48 h after US. We found kappa > 0.45 for focal collection > 1.0 cm (κ = 0.57), hyperemia (κ = 0.57), swirling with compression (κ = 0.52), posterior acoustic enhancement (κ = 0.47), and cobblestoning or branching interstitial fluid (κ = 0.45). Only cobblestoning or interstitial fluid was associated with positive wound cultures in logistic regression models at 8 and 48 h. Cobblestoning or interstitial fluid on US may indicate presence of culture-positive, purulent SSTI in patients without US appearance of abscess. Although our study has limitations due to its retrospective design, this US appearance should alert imagers that the patient may benefit from early I & D.

Estimating local scaling properties for the classification of interstitial lung disease patterns

NASA Astrophysics Data System (ADS)

Huber, Markus B.; Nagarajan, Mahesh B.; Leinsinger, Gerda; Ray, Lawrence A.; Wismueller, Axel

2011-03-01

Local scaling properties of texture regions were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honeycombing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and the estimation of local scaling properties with Scaling Index Method (SIM). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions including the Bonferroni correction. The best classification results were obtained by the set of SIM features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers with the highest accuracy (94.1%, 93.7%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced texture features using local scaling properties can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

Transcapillary fluid shifts in head and neck tissues during and after simulated microgravity

NASA Technical Reports Server (NTRS)

Parazynski, S. E.; Hargens, Alan R.; Tucker, B.; Aratow, M.; Styf, J.; Crenshaw, A.

1991-01-01

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head down for 8 hr, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.2 +/- 5 mm Hg pre-HDT to 33.9 +/- 1.7 mm Hg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, while interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressures dropped significantly after 4 hr of HDT, suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 hr of seated recovery from HDT, microvascular pressures remained significantly elevated by 5 to 8 mm Hg above baseline values, despite a significant HDT diuresis and the orthostatic challenge of an upright, seated posture. During the control (baseline) period, urine output was 46.7 ml/hr; during HDT, it was 126.5 ml/hr. These results indicate that facial edema resulting from HDT is primarily caused by elevated capillary pressures and decreased plasma colloid osmotic pressures. Elevation of cephalic capillary pressures sustained for 4 hr after HDT suggests that there is a compensatory vasodilation to maintain microvascular perfusion. The negativity of interstitial fluid pressures above heart level also has implications for the maintenance of tissue fluid balance in upright posture.

The Effect of Tissue Entrapment on Screw Loosening at the Implant/Abutment Interface of External- and Internal-Connection Implants: An In Vitro Study.

PubMed

Zeno, Helios A; Buitrago, Renan L; Sternberger, Sidney S; Patt, Marisa E; Tovar, Nick; Coelho, Paulo; Kurtz, Kenneth S; Tuminelli, Frank J

2016-04-01

To compare the removal of torque values of machined implant abutment connections (internal and external) with and without soft tissue entrapment using an in vitro model. Thirty external- and 30 internal-connection implants were embedded in urethane dimethacrylate. Porcine tissue was prepared and measured to thicknesses of 0.5 and 1.0 mm. Six groups (n = 10) were studied: External- and internal-connection implants with no tissue (control), 0.5, and 1.0 mm of tissue were entrapped at the implant/abutment interface. Abutments were inserted to 20 Ncm for all six groups. Insertion torque values were recorded using a digital torque gauge. All groups were then immersed in 1 M NaOH for 48 hours to dissolve tissue. Subsequent reverse torque measurements were recorded. Mean and standard deviation were determined for each group, and one-way ANOVA and Bonferroni test were used for statistical analysis. All 60 specimens achieved a 20-Ncm insertion torque, despite tissue entrapment. Reverse torque measurements for external connection displayed a statistically significant difference (p < 0.05) between all groups with mean reverse torque values for the control (13.71 ± 1.4 Ncm), 0.5 mm (7.83 ± 2.4 Ncm), and 1.0 mm tissue entrapment (2.29 ± 1.4 Ncm) groups. Some statistically significant differences (p < 0.05) were found between internal-connection groups. In all specimens, tissue did not completely dissolve after 48 hours. External-connection implants were significantly affected by tissue entrapment; the thicker the tissue, the lower the reverse torque values noted. Internal-connection implants were less affected by tissue entrapment. © 2015 by the American College of Prosthodontists.

Hierarchy and inhomogeneity in the systematic structure of the mammalian myocardium: towards a comprehensive view of cardiodynamics.

PubMed

Lunkenheimer, Paul Peter; Niederer, Peter

2012-01-01

In order to visualise the mammalian myocardial structure in its entirety, we distended excised porcine left ventricles by inflating the coronary arteries with compressed air, using rising pressures between 100 and 300 kPa. The ventricular walls became elongated, and left ventricular cavity widened with rising pressure albeit with insignificant changes in their mural thickness. High resolution computed tomographic analysis subsequent to pneumographic distension revealed a hierarchical structure. First, a feathered arrangement of the cardiomyocytes aggregated together mainly within the equatorial area of the ventricle, giving an overall appearance of systematically arranged spatially netted lamellar structures with pronounced local inhomogeneity. Second, histological examination in orthogonal planes, analysing samples dividing the ventricular walls into 18 segments, showed the lamellae themselves to be made up of aggregated chains of myocytes, the alignment of these chains producing the well-recognised change in so-called helical angle when traced through the thickness of the walls. Transmural length sections removed from the same positions in the ventricular walls showed inter-lamellar connections aligned in the direction from the ventricular base to the apex which were definitely longer than those we observed in transmural cross-sections. Electron-microscopy exposed the two compartments of interstitial connective tissue, suggesting the endomysium to bind long chains of myocytes to lamellar aggregates, while the loose perimysium strengthens the structure of the lubricating medium which eases the gliding of the lamellar aggregates relative to one another.

Exercise and Regulation of Bone and Collagen Tissue Biology.

PubMed

Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja; Magnusson, S Peter

2015-01-01

The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. In contrast to tissue responses with exercise, lack of mechanical tissue loading through inactivity or immobilization of the human body will result in a dramatic loss of connective tissue content, structure, and tolerable load within weeks, to a degree (30-40%) that mimics that of contractile skeletal musculature. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. © 2015 Elsevier Inc. All rights reserved.

Non-malignant chest x ray changes in patients with mesothelioma in a large cohort of asbestos insulation workers.

PubMed Central

Lilis, R; Ribak, J; Suzuki, Y; Penner, L; Bernstein, N; Selikoff, I J

1987-01-01

To assess the prevalence of non-malignant chest x ray abnormalities in cases of mesothelioma 184 cases of mesothelioma (72 pleural and 112 peritoneal) which had occurred in a cohort of asbestos insulation workers followed up since 1967 were studied. Chest x ray films of satisfactory quality, on which the presence or absence of non-malignant radiological changes indicating interstitial pulmonary fibrosis or pleural fibrosis or both, could be assessed with a high degree of certainty were available. In some cases (20% for pleural mesothelioma, 11.6% for peritoneal mesothelioma) non-malignant radiological changes were not radiologically detectable. Parenchymal interstitial fibrosis (small irregular opacities) only was found in a proportion of cases (25.4% of pleural mesotheliomas, 12.5% of peritoneal mesotheliomas). Pleural fibrosis only was detected in 17% of cases of pleural mesothelioma and 27% of cases of peritoneal mesothelioma. Most patients had both parenchymal and pleural fibrosis. Although these results tend to indicate that in peritoneal mesothelioma the proportion of pleural fibrosis is significantly higher, these findings might have been due to the fact that in most cases of pleural mesothelioma non-malignant changes were interpreted in one hemithorax only. In 46 cases (21 pleural, 25 peritoneal) in which sufficient lung tissue was available histopathology of lung parenchyma indicated the presence of interstitial fibrosis; in 20 (43.5%) of these the chest x ray film had been read as negative. Thus the absence of radiologically detectable small opacities on the chest x ray film does not exclude the existence of interstitial pulmonary fibrosis in cases of mesothelioma among insulation workers. With lower levels of exposure (such as in family contacts of asbestos workers) it is conceivable that mesothelioma might occur in the absence of interstitial pulmonary fibrosis. PMID:3606969

MR-guided transcranial focused ultrasound safely enhances interstitial dispersion of large polymeric nanoparticles in the living brain

PubMed Central

Mohammadabadi, Ali; Nguyen, Ben A.; Guo, Sijia; Winkles, Jeffrey A.; Kim, Anthony J.; Gullapalli, Rao; Keller, Asaf; Frenkel, Victor

2018-01-01

Generating spatially controlled, non-destructive changes in the interstitial spaces of the brain has a host of potential clinical applications, including enhancing the delivery of therapeutics, modulating biological features within the tissue microenvironment, altering fluid and pressure dynamics, and increasing the clearance of toxins, such as plaques found in Alzheimer’s disease. Recently we demonstrated that ultrasound can non-destructively enlarge the interstitial spaces of the brain ex vivo. The goal of the current study was to determine whether these effects could be reproduced in the living brain using non-invasive, transcranial MRI-guided focused ultrasound (MRgFUS). The left striatum of healthy rats was treated using MRgFUS. Computer simulations facilitated treatment planning, and targeting was validated using MRI acoustic radiation force impulse imaging. Following MRgFUS treatments, Evans blue dye or nanoparticle probes were infused to assess changes in the interstitial space. In MRgFUS-treated animals, enhanced dispersion was observed compared to controls for 70 nm (12.8 ± 0.9 mm3 vs. 10.6 ± 1.0 mm3, p = 0.01), 200 nm (10.9 ± 1.4 mm3 vs. 7.4 ± 0.7 mm3, p = 0.01) and 700 nm (7.5 ± 0.4 mm3 vs. 5.4 ± 1.2 mm3, p = 0.02) nanoparticles, indicating enlargement of the interstitial spaces. No evidence of significant histological or electrophysiological injury was identified. These findings suggest that transcranial ultrasound can safely and effectively modulate the brain interstitium and increase the dispersion of large therapeutic entities such as particulate drug carriers or modified viruses. This has the potential to expand the therapeutic uses of MRgFUS. PMID:29415084

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Wei-Yu, E-mail: wychen624@cgmh.org.tw; Chang, Ya-Jen; Su, Chia-Hao

Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneysmore » using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases. -- Highlights: •Interleukin (IL)-33 was upregulated in obstructed kidneys. •Interstitial myofibroblasts expressed IL-33 after UUO-induced renal injury. •Deficiency of IL33 reduced interstitial fibrosis and promoted tubular cell proliferation.« less

The interstitial distribution of macromolecules in rat tumours is influenced by the negatively charged matrix components

PubMed Central

Wiig, Helge; Gyenge, Christina C; Tenstad, Olav

2005-01-01

Knowledge of macromolecular distribution volumes is essential in understanding fluid transport within normal and pathological tissues. In this study in vivo we determined the distribution volumes of several macromolecules, including one monoclonal antibody, in tumours and tested whether charges associated with the tumour extracellular matrix influence their available volumes. Steady state levels of the monoclonal antibody trastuzumab (Herceptin) (pI = 9.2), IgG (pI = 7.6) as well as native (pI = 5.0) and cationized albumin (pI = 7.6) were established in rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours by continuous infusion using osmotic minipumps. After a 5–7 day infusion period, the rats were nephrectomized and the extracellular volume was determined with 51Cr-labelled EDTA. Plasma volumes were measured with 125I-labelled human serum albumin or rat IgM in a separate series. Steady state concentrations of probes were determined in the interstitial fluid that was isolated by centrifugation from tumours or by post mortem wick implantation in the back skin. Calculations were made for interstitial fluid volume (Vi), along with the available (Va/Vi) and excluded (Ve/Vi) relative interstitial volume fractions. The Ve/Vi for the positively charged trastuzumab in tumours averaged 0.29 ± 0.03 (n = 16), a value which was significantly lower than the corresponding one for IgG of 0.36 ± 0.02 (n = 16). Native albumin was excluded from 38% of the tumour interstitial fluid, whereas cationization of albumin reduced the excluded volume by ∼50%. Our experiments suggest that the tumour interstitium acts as a negatively charged matrix and is an important factor in determining the macromolecular distribution volume. PMID:15994186

The interstitial distribution of macromolecules in rat tumours is influenced by the negatively charged matrix components.

PubMed

Wiig, Helge; Gyenge, Christina C; Tenstad, Olav

2005-09-01

Knowledge of macromolecular distribution volumes is essential in understanding fluid transport within normal and pathological tissues. In this study in vivo we determined the distribution volumes of several macromolecules, including one monoclonal antibody, in tumours and tested whether charges associated with the tumour extracellular matrix influence their available volumes. Steady state levels of the monoclonal antibody trastuzumab (Herceptin) (pI = 9.2), IgG (pI = 7.6) as well as native (pI = 5.0) and cationized albumin (pI = 7.6) were established in rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours by continuous infusion using osmotic minipumps. After a 5-7 day infusion period, the rats were nephrectomized and the extracellular volume was determined with 51Cr-labelled EDTA. Plasma volumes were measured with 125I-labelled human serum albumin or rat IgM in a separate series. Steady state concentrations of probes were determined in the interstitial fluid that was isolated by centrifugation from tumours or by post mortem wick implantation in the back skin. Calculations were made for interstitial fluid volume (Vi), along with the available (Va/Vi) and excluded (Ve/Vi) relative interstitial volume fractions. The Ve/Vi for the positively charged trastuzumab in tumours averaged 0.29 +/- 0.03 (n = 16), a value which was significantly lower than the corresponding one for IgG of 0.36 +/- 0.02 (n = 16). Native albumin was excluded from 38% of the tumour interstitial fluid, whereas cationization of albumin reduced the excluded volume by approximately 50%. Our experiments suggest that the tumour interstitium acts as a negatively charged matrix and is an important factor in determining the macromolecular distribution volume.

Retinoid agonist isotretinoin ameliorates obstructive renal injury.

PubMed

Schaier, Matthias; Jocks, Thomas; Grone, Hermann-Josef; Ritz, Eberhard; Wagner, Juergen

2003-10-01

Interstitial fibrosis is a major cause of end stage renal failure. Retinoids, which are involved in tissue repair and fibrosis, inhibit inflammatory and proliferative pathways. Therefore, we studied the dose dependent effects of the retinoid receptor agonist isotretinoin 13-cis retinoic acid in the unilateral ureteral obstruction model (UUO). Sham operated control rats were compared with UUO rats treated with vehicle (UUO-Veh), or low (5 mg/kg body weight (UUO-LD) or high (25 mg/kg) (UUO-HD) dose isotretinoin. Kidneys were evaluated using reverse transcriptase-polymerase chain reaction and immunohistology 7 days after UUO. Renal injury and fibrosis were quantified by immunostaining and expression measurements of the genes involved in renal fibrosis. In UUO-Veh kidneys the interstitial area was expanded 5-fold but only 3-fold in UUO-HD and 3.5-fold in UUO-LD rats. Interstitial cell counts were 3-fold higher in UUO-Veh rats but significantly less in UUO-HD or UUO-LD animals. Tubular and interstitial cell proliferation was significantly higher in UUO-Veh rats compared with sham operated control plus vehicle animals but less so in UUO-LD and UUO-HD rats. In UUO-Veh rats interstitial infiltration by monocytes/macrophages was higher compared with unobstructed controls. It was significantly less after isotretinoin treatment. In UUO-Veh rats mRNA for procollagen I, and transforming growth factor-beta1 and II receptor was significantly increased. It was significantly less after treatment with isotretinoin. Fibronectin and collagen I immunostaining was also decreased by isotretinoin. Since isotretinoin limits proliferation, inflammation and fibrosis after UUO, retinoids should be further investigated as potentially promising therapeutic agents for renal disease.

Effect of houttuynia cordata aetherolea on adiponectin and connective tissue growth factor in a rat model of diabetes mellitus.

PubMed

Wang, Hai-Ying; Bao, Jun-Lu

2012-03-01

To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus (DM). DM was induced in rats using streptozotocin (STZ) and high glucose-lipid animal feed. Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks. Changes in connective tissue growth factor and adiponectin levels in rats were observed. Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment. Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.

Diabetes-Induced Decrease in Renal Oxygen Tension: Effects of an Altered Metabolism

NASA Astrophysics Data System (ADS)

Palm, Fredrik; Carlsson, Per-Ola; Fasching, Angelica; Hansell, Peter; Liss, Per

During conditions with experimental diabetes mellitus, it is evident that several alterations in renal oxygen metabolism occur, including increased mitochondrial respiration and increased lactate accumulation in the renal tissue. Consequently, these alterations will contribute to decrease the interstitial pO2, preferentially in the renal medulla of animals with sustained long-term hyperglycemia.

Experiment K-6-02. Biomedical, biochemical and morphological alterations of muscle and dense, fibrous connective tissues during 14 days of spaceflight

NASA Technical Reports Server (NTRS)

Vailas, A.; Zernicke, R.; Grindeland, R.; Kaplanski, A.

1990-01-01

Findings on the connective tissue response to short-term space flight (12 days) are discussed. Specifically, data regarding the biochemical, biomechanical and morphological characteristics of selected connective tissues (humerus, vertebral body, tendon and skeletal muscle) of growing rats is given. Results are given concerning the humerus cortical bone, the vertebral bone, nutritional effects on bone biomechanical properties, and soft tense fiber connective tissue response.

Effects of large pressure amplitude low frequency noise in the parotid gland perivasculo-ductal connective tissue.

PubMed

Oliveira, Pedro; Brito, José; Mendes, João; da Fonseca, Jorge; Águas, Artur; Martins dos Santos, José

2013-01-01

In tissues and organs exposed to large pressure amplitude low frequency noise fibrosis occurs in the absence of inflammatory signs, which is thought to be a protective response. In the parotid gland the perivasculo-ductal connective tissue surrounds arteries, veins and the ductal tree. Perivasculo-ductal connective tissue is believed to function as a mechanical stabilizer of the glandular tissue. In order to quantify the proliferation of perivasculo-ductal connective tissue in large pressure amplitude low frequency noise-exposed rats we used sixty Wistar rats which were equally divided into 6 groups. One group kept in silence, and the remaining five exposed to continuous large pressure amplitude low frequency noise: g1-168h (1 week); g2-504h (3 weeks); g3-840h (5 weeks); g4-1512h (9 weeks); and g5-2184h (13 weeks). After exposure, parotid glands were removed and the perivasculo-ductal connective tissue area was measured in all groups. We applied ANOVA statistical analysis, using SPSS 13.0. The global trend is an increase in the average perivasculo-ductal connective tissue areas, that develops linearly and significantly with large pressure amplitude low frequency noise exposure time (p < 0.001). It has been suggested that the biological response to large pressure amplitude low frequency noise exposure is associated with the need to maintain structural integrity. The structural reinforcement would be achieved by increased perivasculo-ductal connective tissue. Hence, these results show that in response to large pressure amplitude low frequency noise exposure, rat parotid glands increase their perivasculo-ductal connective tissue.

The diagnosis efficacy and safety of video-assisted thoracoscopy surgery (VATS) in undefined interstitial lung diseases: a retrospective study

PubMed Central

Luo, Qun; Han, Qian; Chen, Xiaobo; Xie, Jiaxing; Wu, Lulu

2013-01-01

Objectives To evaluate the efficacy and safety of lung biopsies by video-assisted thoracoscopy surgery (VATS) in the diagnosis of undefined interstitial lung disease (ILD). Patients and methods The retrospective analysis was performed in 32 who patients underwent VATS for the diagnosed with ILD from Jan 2007 to Dec 2011. The main reason for VATS for all the patients was due to no specific diagnosis could be obtained after non-invasive methods, transbronchial lung biopsy (TBLB) examination and the consultation with pulmonologist, radiologist and pathologist. The clinical profiles, chest high resolution computerized tomography (HRCT), laboratory profile, TBLB as well as the diagnosis of before and after the VATS were analyzed. The surgery site, biopsy number, duration of the thoracic drain, post-operative complications were also recorded. The 30- and 90-day post-operative mortality rates were calculated. The risk factors associated with the incidence of post-operative complications were assessed. Results The specific diagnosis could be established in all patients after VATS lung biopsies, with change from previous ones in 27 (84.4%). Among 20 cases (62.5%) diagnosed as unclassified ILD before the surgery, 14 (70.0%) were diagnosed as nonspecific interstitial pneumonia (NSIP), 3 (15.0%) as idiopathic pulmonary fibrosis (IPF) and 3 (15.0%) as connective tissue disease-related ILD (CTD-ILD). Among the 7 cases with complete change of diagnosis after VATS, 4 (57.1%) were cryptogenic organizing pneumonia (COP). The number of site of biopsy had no significant impact on the diagnostic efficacy. There were no significant change of vital sign and lung function after the VATS. 21 (65.6%) patients had post-operative complications, including pulmonary infection (56.3%), pulmonary atelectasis (28.1%) and pneumothorax (25.0%). The 30- and 90-day mortality rates were 0 and 5.2% respectively. Patients were divided into 2 groups based on the incidence of post-operative complications, and no significant difference was found in regards to the age, body mass index (BMI), smoking index, lung function, anesthesia method, duration of remaining the thoracic drain and the use of immunosuppressive drugs or steroids. Conclusions VATS is a safe and effective procedure for the diagnosis of ILD which were unclassified after routine evaluation, transbronchial lung biopsy and consultation with pulmonologist, radiologist and pathologist. PMID:23825760

Caprine Abscess Model of Tulathromycin Concentrations in Interstitial Fluid from Tissue Chambers Inoculated with Corynebacterium pseudotuberculosis following Subcutaneous or Intrachamber Administration

PubMed Central

Fajt, V. R.; Lawhon, S. D.; Adams, L. G.; Tell, L. A.; Bissett, W. T.

2013-01-01

Corynebacterium pseudotuberculosis causes chronic, suppurative, abscessing conditions in livestock and humans. We used an in vivo model to evaluate antimicrobial efficacy for focal abscesses caused by C. pseudotuberculosis. Tissue chambers were surgically implanted in the subcutaneous tissues of the right and left paralumbar fossa of 12 goats to serve as a model for isolated, focal abscesses. For each goat, one tissue chamber was inoculated with C. pseudotuberculosis, while the contralateral chamber served as an uninoculated control. Six goats were administered a single dose of tulathromycin at 2.5 mg/kg of body weight subcutaneously, while the other six received the same dose by injection directly into the inoculated chambers. Our objective was to compare the effects and tulathromycin concentrations in interstitial fluid (IF) samples collected from C. pseudotuberculosis-infected and control chambers following subcutaneous or intrachamber injection of tulathromycin. In addition, the effects of tulathromycin on the quantity of C. pseudotuberculosis reisolated from inoculated chambers were assessed over time. Tulathromycin IF concentrations from C. pseudotuberculosis-infected and control tissue chambers were similar to those in plasma following subcutaneous administration. Following intrachamber administration, tulathromycin IF concentrations in infected chambers were continuously above the MIC for the C. pseudotuberculosis isolate for 15 days. There were no significant differences for plasma area under the curve and elimination half-lives between subcutaneous and intrachamber administration. Six of the 12 infected chambers had no growth of C. pseudotuberculosis 15 days postadministration. Results of this study indicate that tulathromycin may be beneficial in the treatment of focal infections such as those caused by C. pseudotuberculosis. PMID:24100501

Effects of Anti-VEGF on Predicted Antibody Biodistribution: Roles of Vascular Volume, Interstitial Volume, and Blood Flow

PubMed Central

Boswell, C. Andrew; Ferl, Gregory Z.; Mundo, Eduardo E.; Bumbaca, Daniela; Schweiger, Michelle G.; Theil, Frank-Peter; Fielder, Paul J.; Khawli, Leslie A.

2011-01-01

Background The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. Methodology/Principal Findings Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. Conclusions/Significance These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF. PMID:21436893

An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes

PubMed Central

Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J.; Targoff, Ira N.; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

2014-01-01

Abstract Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n = 2 patients), Nup90 (n = 1), Nup62 (n = 1), and gp210 (n = 1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1∗0501 allele associated with an increased risk for autoimmune myositis. In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an “anti-nup syndrome.” PMID:25500708

Protein vs electrolytes and all of the Starling forces.

PubMed

Peters, R M; Hargens, A R

1981-10-01

Hemodilution-induced reductions of the intravascular protein concentration in patients and experimental animals with intact capillaries do not lead to pulmonary edema, despite significant increases in the amount of extravascular water in the systemic interstitial space. The protective factors are a drop in the extravascular concentration of protein, a rise in interstitial tissue pressure, and an increase in lymph flow. If the capillary endothelium is damaged, protein leaks into the extravascular space, and protein infusion has a diminished effect on fluid exchange across the capillary. Whether capillaries are intact or injured, prevention of increases in capillary hydrostatic pressure is the most important factor in preventing pulmonary edema. Administration of hypertonic fluids may provide a useful method of limiting total fluid infusion and reducing cell swelling after blood loss.

Intermediate-grade mammary gland adenocarcinoma in an 18-year-old female black leopard (Panthera pardus) with acute pancreatic necrosis and chronic interstitial nephropathy.

PubMed

Nakamura, Misato; Yoshida, Toshinori; Eguchi, Ayumi; Inohana, Mari; Nagahara, Rei; Shiraki, Ayako; Ito, Nanao; Shibutani, Makoto

2018-03-02

An 18-year-old female black leopard (Panthera pardus) showed renal failure, leukocytosis and presence of subcutaneous masses in the lower abdominal region and right shoulder; she eventually died. Histopathological observations included a mammary gland carcinoma with comedo, solid and tubulopapillary patterns in subcutaneous tissue, and highly proliferated tumor cells in systemic organs. The tumor cells were positive for cytokeratin AE1/AE3. The mammary gland tumor was diagnosed as intermediate-grade adenocarcinoma, based on a previously reported histological grading system of feline mammary carcinomas. Chronic interstitial nephritis was estimated to have been ongoing for 5 years, whilst acute necrotic pancreatitis in relation to tumor metastasis could have been the cause of death.

Master Amino acid Pattern as sole and total substitute for dietary proteins during a weight-loss diet to achieve the body's nitrogen balance equilibrium.

PubMed

Lucà-Moretti, M; Grandi, A; Lucà, E; Muratori, G; Nofroni, M G; Mucci, M P; Gambetta, P; Stimolo, R; Drago, P; Giudice, G; Tamburlin, N; Karbalai, M; Valente, C; Moras, G

2003-01-01

Results of this multicentric study have shown that by giving Master Amino acid Pattern (MAP) as a sole and total substitute of dietary proteins to 500 overweight participants undergoing the American Nutrition Clinics/Overweight Management Program (ANC/OMP), the participants' body nitrogen balance could be maintained in equilibrium with essentially no calories (MAP 1 g=0.04 kcal), thereby preserving the body's structural and functional proteins, eliminating excessive water retention from the interstitial compartment, and preventing the sudden weight increase after study conclusion commonly known as the yo-yo effect. Study results have shown that the use of MAP, in conjunction with the ANC/OMP regimen, has proven to be safe and effective by preventing those adverse effects associated with a negative nitrogen balance, such as oversized or flabby tissue, stretch marks, the sagging of breast tissue, increased hair loss, faded hair color, and fragile or brittle nails. Also prevented were those anomalies commonly associated with weight-loss diets, such as hunger, weakness, headache caused by ketosis, constipation, and decreased libido. The use of MAP in conjunction with the ANC/OMP also allowed for mean weight loss of 2.5 kg (5.5 lb) per week, achieved through reduction of excessive fat tissue and elimination of excessive water retention from the interstitial compartment.

Effect of dietary melengestrol acetate on the incidence of acute interstitial pneumonia in feedlot heifers

PubMed Central

McAllister, Tim A.; Ayroud, Mejid; Bray, Tammy M.; Yost, Garold S.

2006-01-01

Abstract Over a 3-y period, 906 000 cattle were monitored in 23 feedlots in southern Alberta for symptoms of acute interstitial pneumonia (AIP). Plasma, urine, and lung tissue were collected at slaughter from 299 animals clinically diagnosed with AIP and from 156 healthy penmates and analyzed for 3-methylindole (3MI) derivatives and reduced glutathione concentration. From each animal, the left lung was subsampled for histologic examination. Concentrations of glutathione in lung tissue were reduced (P < 0.001) in animals showing clinical symptoms of AIP as compared with their asymptomatic penmates. Animals histologically confirmed as having AIP had higher levels of 3MI protein adducts in blood and lung tissue (P < 0.05) than did emergency-slaughtered animals without AIP. Within feedlots, where pens of heifers were fed either a standard dosage of melengestrol acetate (MGA) or none, the rate of death attributable to AIP was similar between treatment groups, but emergency slaughter after clinical diagnosis of AIP was done 3.2 times more often (P < 0.001) in the MGA-fed heifers than in the group not fed MGA. Use of MGA did not influence glutathione concentration. As growth performance of heifers given steroidal implants may not be improved by feeding MGA, the most cost-effective method of reducing the incidence of AIP-related emergency slaughter in feedlot heifers may be to eliminate MGA from the diet. PMID:16850945

Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla.

PubMed

Pijnenborg, R; Vercruysse, L; Carter, A M

2011-08-01

In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings in the chimpanzee, we postulated the occurrence of deep invasion in gorilla pregnancy. Tissues were processed for histology (PAS, orcein), lectin staining (Ulex europaeus agglutinin 1) and immunohistochemistry (cytokeratin 7/17, α-actin). A specimen of young but undetermined gestational age included deep placental bed tissue, showing interstitial and spiral artery invasion of the inner myometrium as well as the decidua. The cell density and depth of trophoblast invasion was equivalent to a human placental bed of 10-14 weeks. Intraluminal trophoblasts were not seen in any of the invaded vessels, allowing no definite conclusions about the origin of the intramural trophoblast and the time-course of spiral artery invasion. A different late second trimester placenta specimen showed scattered extravillous trophoblast in the basal plate and underlying decidua, as well as a remodelled spiral artery containing intramural trophoblast. Absence of inner myometrial tissue precluded assessment of invasion depth in this later specimen. Despite the limited material we can conclude that key aspects of trophoblast invasion are shared by the three hominid species: gorilla, chimpanzee and human. Copyright © 2011 Elsevier Ltd. All rights reserved.

Collapsing granular beds: the role of interstitial air.

PubMed

Homan, Tess; Gjaltema, Christa; van der Meer, Devaraj

2014-05-01

A prefluidized sand bed consisting of fine particles compactifies when it is subjected to a shock. We observe that the response depends on both the shock strength and the ambient pressure, where, counterintuitively, at high ambient pressure the compaction is larger, which we connect to a decrease of the static friction inside the bed. We find that the interstitial air is trapped inside the bed during and long after compaction. We deduce this from measuring the pressure changes above and below the bed: The top pressure decreases abruptly, on the time scale of the compaction, whereas that below the bed slowly rises to a maximum. Subsequently, both gently relax to ambient values. We formulate a one-dimensional diffusion model that uses only the change in bed height and the ambient pressure as an input, and we show that it leads to a fully quantitative understanding of the measured pressure variations.

Nuclear Mechanics in Cancer

PubMed Central

Denais, Celine; Lammerding, Jan

2015-01-01

Despite decades of research, cancer metastasis remains an incompletely understood process that is as complex as it is devastating. In recent years, there has been an increasing push to investigate the biomechanical aspects of tumorigenesis, complementing the research on genetic and biochemical changes. In contrast to the high genetic variability encountered in cancer cells, almost all metastatic cells are subject to the same physical constraints as they leave the primary tumor, invade surrounding tissues, transit through the circulatory system, and finally infiltrate new tissues. Advances in live cell imaging and other biophysical techniques, including measurements of subcellular mechanics, have yielded stunning new insights into the physics of cancer cells. While much of this research has been focused on the mechanics of the cytoskeleton and the cellular microenvironment, it is now emerging that the mechanical properties of the cell nucleus and its connection to the cytoskeleton may play a major role in cancer metastasis, as deformation of the large and stiff nucleus presents a substantial obstacle during the passage through the dense interstitial space and narrow capillaries. Here, we present an overview of the molecular components that govern the mechanical properties of the nucleus and we discuss how changes in nuclear structure and composition observed in many cancers can modulate nuclear mechanics and promote metastatic processes. Improved insights into this interplay between nuclear mechanics and metastatic progression may have powerful implications in cancer diagnostics and therapy and may reveal novel therapeutic targets for pharmacological inhibition of cancer cell invasion. PMID:24563360

The Emerging Relationship Between Interstitial Fluid-Cerebrospinal Fluid Exchange, Amyloid-β, and Sleep.

PubMed

Boespflug, Erin L; Iliff, Jeffrey J

2018-02-15

Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD. Aβ, like many interstitial solutes, is cleared in part through the exchange of brain interstitial fluid and cerebrospinal fluid along a brain-wide network of perivascular pathways recently termed the glymphatic system. Glymphatic function is primarily a feature of the sleeping brain, rather than the waking brain, and is slowed in the aging and posttraumatic brain. These changes may underlie the diurnal fluctuations in interstitial and cerebrospinal fluid Aβ levels observed in both the rodent and the human. These and other emerging studies suggest that age-related sleep disruption may be one key factor that renders the aging brain vulnerable to Aβ deposition and the development of AD. If this is true, sleep may represent a key modifiable risk factor or therapeutic target in the preclinical phases of AD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Mueller matrix approach for probing multifractality in the underlying anisotropic connective tissue

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Dey, Rajib; Ghosh, Nirmalya

2016-09-01

Spatial variation of refractive index (RI) in connective tissues exhibits multifractality, which encodes useful morphological and ultrastructural information about the disease. We present a spectral Mueller matrix (MM)-based approach in combination with multifractal detrended fluctuation analysis (MFDFA) to exclusively pick out the signature of the underlying connective tissue multifractality through the superficial epithelium layer. The method is based on inverse analysis on selected spectral scattering MM elements encoding the birefringence information on the anisotropic connective tissue. The light scattering spectra corresponding to the birefringence carrying MM elements are then subjected to the Born approximation-based Fourier domain preprocessing to extract ultrastructural RI fluctuations of anisotropic tissue. The extracted RI fluctuations are subsequently analyzed via MFDFA to yield the multifractal tissue parameters. The approach was experimentally validated on a simple tissue model comprising of TiO2 as scatterers of the superficial isotropic layer and rat tail collagen as an underlying anisotropic layer. Finally, the method enabled probing of precancer-related subtle alterations in underlying connective tissue ultrastructural multifractality from intact tissues.

Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

2016-10-01

Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

Cells of the connective tissue differentiate and migrate into pollen sacs

NASA Astrophysics Data System (ADS)

Iqbal, M. C. M.; Wijesekara, Kolitha B.

2002-01-01

In angiosperms, archesporial cells in the anther primordium undergo meiosis to form haploid pollen, the sole occupants of anther sacs. Anther sacs are held together by a matrix of parenchyma cells, the connective tissue. Cells of the connective tissue are not known to differentiate. We report the differentiation of parenchyma cells in the connective tissue of two Gordonia species into pollen-like structures (described as pseudopollen), which migrate into the anther sacs before dehiscence. Pollen and pseudopollen were distinguishable by morphology and staining. Pollen were tricolpate to spherical while pseudopollen were less rigid and transparent with a ribbed surface. Both types were different in size, shape, staining and surface architecture. The ratio of the number of pseudopollen to pollen was 1:3. During ontogeny in the connective tissue, neither cell division nor tetrad formation was observed and hence pseudopollen were presumed to be diploid. Only normal pollen germinated on a germination medium. Fixed preparations in time seemed to indicate that pseudopollen migrate from the connective tissue into the anther sac.

Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods.

PubMed

Nagahashi, Masayuki; Yamada, Akimitsu; Miyazaki, Hiroshi; Allegood, Jeremy C; Tsuchida, Junko; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P; Adams, Barbara J; Rashid, Omar M; Milstien, Sheldon; Wakai, Toshifumi; Spiegel, Sarah; Takabe, Kazuaki

2016-06-01

The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment.

Photoacoustic physio-chemical analysis for prostate cancer diagnosis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Guan; Cheng, Qian; Huang, Shengsong; Qin, Ming; Hopkins, Thomas; Lee, Chang H.; Kopelman, Raoul; Chao, Wan-yu; Keller, Evan T.; Wu, Denglong; Wang, Xueding

2017-03-01

Photoacoustic physio-chemical analysis (PAPCA) is a recently developed technology capable of simultaneously quantifying the content of molecular components and the corresponding microarchitectures in biological tissue. We have successfully quantified the diagnostic information in livers with PAPCA. In this study, we implemented PAPCA to the diagnosis of prostate cancers. 4 human prostates were scanned ex vivo. The PA signals from normal and cancerous regions in the prostates were acquired by an interstitial needle PA probe. A total of 14 interstitial measurements, including 6 within the normal regions and 8 in the cancerous regions, were acquired. The observed changes in molecular components, including lipid, collagen and hemoglobin were consistent with the findings by other research groups. The changes were quantified by PA spectral analysis (PASA) at wavelengths where strong optical absorption of the relevant molecular components was found. Statistically significant differences among the PASA parameters were observed (p=0.025 at significance of 0.05). A support vector machine model for differentiating the normal and cancerous tissue was established. With the limited number of samples, an 85% diagnostic accuracy was found. The diagnostic information in the PCPCA can be further enriched by targeted optical contrast agents visualizing the microarchitecture in PCa tissues. F3 PAA-PEG nanoparticles was employed to stain the PCa cells in a transgenic mouse model, in which the microarchitectures of normal and cancerous prostate tissues are comparable to that in human. Statistically significant differences were observed between the contrast-enhanced normal and cancerous regions (p=0.038 at a significance of 0.05).

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study.

PubMed

Agarwal, Ashish; Gupta, Narinder Dev

2015-01-01

Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

The Rationale for Joint Mobilization.

ERIC Educational Resources Information Center

Burkhardt, Sandy

This paper presents an overview of the functions of connective tissue and the mechanisms of joint injury and contracture formation in relation to therapeutic exercise. The components of connective tissue operation are explained, including fibroblasts, macrophages, plasma cells, and collagen. An examination of the histology of connective tissue as…

CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

PubMed Central

Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

2013-01-01

The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function and cancer. PMID:23444198

Miniaturization of Microwave Ablation Antennas

NASA Astrophysics Data System (ADS)

Luyen, Hung

Microwave ablation (MWA) is a promising minimally invasive technique for the treatment of various types of cancers as well as non-oncological diseases. In MWA, an interstitial antenna is typically used to deliver microwave energy to the diseased tissue and heat it up to lethal temperature levels that induce cell death. The desired characteristics of the interstitial antenna include a narrow diameter to minimize invasiveness of the treatment, a low input reflection coefficient at the operating frequency, and a localized heating zone. Most interstitial MWA antennas are fed by coaxial cables and designed for operation at either 915 MHz or 2.45 GHz. Coax-fed MWA antennas are commonly equipped with coaxial baluns to achieve localized heating. However, the conventional implementation of coaxial baluns increases the overall diameters of the antennas and therefore make them more invasive. It is highly desirable to develop less invasive antennas with shorter active lengths and smaller diameters for MWA applications. In this work, we demonstrate the feasibility of using higher frequency microwaves for tissue ablation and present several techniques for decreasing diameters of MWA antennas. First, we investigated MWA at higher frequencies by conducting numerical and experimental studies to compare ablation performance at 10 GHz and 1.9 GHz. Simulation and ex vivo ablation experiment results demonstrate comparable ablation zone dimensions achieved at these two frequencies. Operating at higher frequencies enables interstitial antennas with shorter active lengths. This can be combined with smaller-diameter antenna designs to create less invasive applicators or allow integration of multiple radiating elements on a single applicator to have better control and customization of the heating patterns. Additionally, we present three different coax-fed antenna designs and a non-coaxial-based balanced antenna that have smaller-diameter configurations than conventional coax-fed balun-equipped antennas. The antennas were evaluated and optimized in electromagnetic and thermal simulations. Then prototypes of these antennas were fabricated and experimentally characterized in ex vivo ablation experiments. Simulation and experimental results are in good agreement and demonstrate that the proposed antennas provide good impedance matching and localized heating patterns at their operating frequencies while having about 30% smaller diameters compared to conventional coax-fed balun-equipped MWA antennas.

Feasibility of using interstitial ultrasound for intradiscal thermal therapy: a study in human cadaver lumbar discs

NASA Astrophysics Data System (ADS)

Nau, William H.; Diederich, Chris J.; Shu, Richard

2005-06-01

Application of heat in the spine using resistive wire heating devices is currently being used clinically for minimally invasive treatment of discogenic low back pain. In this study, interstitial ultrasound was evaluated for the potential to heat intradiscal tissue more precisely by directing energy towards the posterior annular wall while avoiding vertebral bodies. Two single-element directional applicator design configurations were tested: a 1.5 mm OD direct-coupled (DC) applicator which can be implanted directly within the disc, and a catheter-cooled (CC) applicator which is inserted in a 2.4 mm OD catheter with integrated water cooling and implanted within the disc. The transducers were sectored to produce 90° spatial heating patterns for directional control. Both applicator configurations were evaluated in four human cadaver lumbar disc motion segments. Two heating protocols were employed in this study in which the temperature measured 5 mm away from the applicator was controlled to either T = 52 °C, or T > 70 °C for the treatment period. These temperatures (thermal doses) are representative of those required for thermal necrosis of in-growing nociceptor nerve fibres and disc cellularity alone, or with coagulation and restructuring of annular collagen in the high-temperature case. Steady-state temperature maps, and thermal doses (t43) were used to assess the thermal treatments. Results from these studies demonstrated the capability of controlling temperature distributions within selected regions of the disc and annular wall using interstitial ultrasound, with minimal vertebral end-plate heating. While directional heating was demonstrated with both applicator designs, the CC configuration had greater directional heating capabilities and offered better temperature control than the DC configuration, particularly during the high-temperature protocol. Further, ultrasound energy was capable of penetrating within the highly attenuating disc tissue to produce more extensive radial thermal penetration, lower maximum intradiscal temperature, and shorter treatment times than can be achieved with current clinical intradiscal heating technology. Thus, interstitial ultrasound offers potential as a more precise and faster heating modality for the clinical management of low back pain.

Roles of CD34+ cells and ALK5 signaling in the reconstruction of seminiferous tubule-like structures in 3-D re-aggregate culture of dissociated cells from neonatal mouse testes.

PubMed

Abe, Shin-Ichi; Abe, Kazuko; Zhang, Jidong; Harada, Tomoaki; Mizumoto, Go; Oshikawa, Hiroki; Akiyama, Haruhiko; Shimamura, Kenji

2017-01-01

Tissue reconstruction in vitro can provide, if successful, a refined and simple system to analyze the underlying mechanisms that drive the morphogenesis and maintain the ordered structure. We have recently succeeded in reconstruction of seminiferous cord-like and tubule-like structures using 3-D re-aggregate culture of dissociated testicular cells. In testis formation, endothelial cells that migrated from mesonephroi to embryonic gonads have been shown to be critical for development of testis cords, but how endothelial cells contribute to testis cord formation remains unknown. To decipher the roles of endothelial and peritubular cells in the reconstruction of cord-like and tubule-like structures, we investigated the behavior of CD34+ endothelial and p75+ cells, and peritubular myoid cells (PTMCs) in 3-D re-aggregate cultures of testicular cells. The results showed that these 3 types of cells had the capacity of re-aggregation on their own and with each other, and of segregation into 3 layers in a re-aggregate, which were very similar to interstitial and peritubular tissues in vivo. Observation of behaviors of fluorescent Sertoli cells and other non-fluorescent types of cells using testes from Sox9-EGFP transgenic mice showed dynamic cell movement and segregation in re-aggregate cultures. Cultures of testicular cells deprived of interstitial and peritubular cells resulted in dysmorphic structures, but re-addition of them restored tubule-like structures. Purified CD34+ cells in culture differentiated into p75+ cells and PTMCs. These results indicate that CD34+ cells differentiate into p75+ cells, which then differentiate into PTMCs. TGFβ signaling inhibitors, SB431542 and ALK5i, disturbed the reconstruction of cord-like and tubule-like structures, and the latter compromised re-construction of interstitial-like and peritubular-like structures, as well as the proliferation of CD34+, p75+, PTMCs, and Sertoli cells, and their movement and differentiation. These results indicate that CD34+ cells and signaling through ALK5 play pivotal roles in the morphogenesis of interstitial-like, peritubular-like and cord-like structures.

Virchow-Robin space and aquaporin-4: new insights on an old friend.

PubMed

Nakada, Tsutomu

2014-08-28

Recent studies have strongly indicated that the classic circulation model of cerebrospinal fluid (CSF) is no longer valid. The production of CSF is not only dependent on the choroid plexus but also on water flux in the peri-capillary (Virchow Robin) space. Historically, CSF flow through the Virchow Robin space is known as interstitial flow, the physiological significance of which is now fully understood. This article briefly reviews the modern concept of CSF physiology and the Virchow-Robin space, in particular its functionalities critical for central nervous system neural activities. Water influx into the Virchow Robin space and, hence, interstitial flow is regulated by aquaporin-4 (AQP-4) localized in the endfeet of astrocytes, connecting the intracellular cytosolic fluid space of astrocytes and the Virchow Robin space. Interstitial flow has a functionality equivalent to systemic lymphatics, on which clearance of β-amyloid is strongly dependent. Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating. Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels. This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases.

PubMed

Meng, Peng; Tan, Gan Liang; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

2016-12-01

Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients' final diagnoses based on multi-disciplinary consensus. One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24-79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited.

Coelomic epithelium-derived cells in visceral morphogenesis.

PubMed

Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

2016-03-01

Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. © 2015 Wiley Periodicals, Inc.

Imaging of connective tissue diseases of the head and neck

PubMed Central

2016-01-01

We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren’s syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still’s disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders. PMID:26988082

Biliopancreatic duct injection of ethanol as an experimental model of acute and chronic pancreatitis in rats

PubMed Central

Unal, Ethem; Atalay, Suleyman; Tolan, Huseyin Kerem; Yuksekdag, Sema; Yucel, Metin; Acar, Aylin; Basak, Fatih; Gunes, Pembegul; Bas, Gurhan

2015-01-01

In the present study, we described an easily reproducable experimental pancreatits model induced by biliopancreatic duct injection of ethyl alcohol. Seventy Wistar albino rats were divided equally into seven groups randomly: the control group (group 1), acute pancreatitis groups; induced by 20% ethanol (group 2), 48% ethanol (group 3), 80% ethanol (group 4), chronic pancreatitis groups; induced by 20% ethanol (group 5), 48% ethanol (group 6) and by 80% ethanol (group 7). Acute pancreatitis groups were sacrified on postoperative day 3, while the control group and chronic pancreatitis groups were killed on postoperative day 7. Histopathologic evaluation was done, and P < 0.05 was accepted as statistically significant. All rats in group 3 developed acute pancreatitis (100%). Inflammatory infiltration of neutrophils and mononuclear cells, interstitial edema, and focal necrotic areas were seen in the pancreatic tissues. Similarly, all rats in group 6 developed chronic pancreatitis (100%). Interstitial fibrosis, lymphotic infiltration, ductal dilatation, acinar cell atrophy, periductal hyperplasia were seen in the pancreatic tissues. Mortality was seen only in group 7. The biliopancreatic ductal injection of 48% ethanol induced acute and chronic pancreatitis has 100% success rate. PMID:25785001

Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients.

PubMed

Olivieri, Carmela; Bargagli, Elena; Inghilleri, Simona; Campo, Ilaria; Cintorino, Marcella; Rottoli, Paola

2016-06-01

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disorder characterized by a pattern of Usual Interstitial Pneumonia where the presence of fibroblastic foci is the hallmark of the disease. In the present study, we analyzed the migration inhibitory factor (MIF) expression in lung tissue of IPF patients compared with healthy controls and organizing pneumonia (OP) patients focusing into MIF potential role in fibroblastic foci development. The immunohistochemical analysis was performed in 10 IPF patients (7 male), 3 OP patients (2 male), and 3 healthy controls (all male) using the streptavidin-biotin method (Dako). In IPF samples, MIF resulted overexpressed in the areas of active fibrosis and, in particular, in the alveolar epithelium, bronchiolar epithelium, and in the peripheral zones of fibroblastic foci. Bronchiolar epithelium from organizing pneumonia patients resulted only weakly positive for MIF while no evidence of MIF expression was reported for alveolar epithelium. In the control subject group, MIF was unexpressed except for a weak presence in the bronchiolar epithelium. In conclusion, MIF is a pleiotropic cytokine involved in the pathogenesis of IPF being mainly expressed in the areas of remodeling and active fibrosis, in bronchiolar and alveolar epithelium, and in the peripheral zone of fibroblastic foci.

Cerebriform connective tissue nevus of lumbar.

PubMed

Chen, Jinbo; Chen, Liuqing; Duan, Yiqun; Li, Dongsheng; Dong, Bilin

2015-02-01

Connective tissue nevi represents a kind of hamartoma, and coalescence of the lesions in a cerebriform mode in the lumbar region without Proteus syndrome is rarely seen. Here, we report a 26-year-old woman presenting with nodules and plaques in her left lumbar region of 26 years in duration. Histopathological examination and Masson-trichrome stain showed increased dermal collagen bundles in a haphazard array. The diagnosis of connective tissue nevi was made. This is the first case report on cerebriform connective tissue nevi without Proteus syndrome in the lumbar region. © 2014 Japanese Dermatological Association.

The peri-esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging.

PubMed

Weijs, T J; Goense, L; van Rossum, P S N; Meijer, G J; van Lier, A L H M W; Wessels, F J; Braat, M N G; Lips, I M; Ruurda, J P; Cuesta, M A; van Hillegersberg, R; Bleys, R L A W

2017-02-01

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named 'aorto-esophageal ligament' and the layer connecting aorta to the right pleural reflection 'aorto-pleural ligament'. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named 'peri-esophageal compartment' and the posterior compartment 'para-aortic compartment'. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long-standing paradigm that no such structure exists. A comprehensive, detailed description of the peri-esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI. © 2016 Anatomical Society.

Association between antinuclear antibody titers and connective tissue diseases in a Rheumatology Department.

PubMed

Menor Almagro, Raúl; Rodríguez Gutiérrez, Juan Francisco; Martín-Martínez, María Auxiliadora; Rodríguez Valls, María José; Aranda Valera, Concepción; de la Iglesia Salgado, José Luís

To determine the dilution titles at antinuclear antibodies (ANA) by indirect immunofluorescence observed in cell substrate HEp-2 and its association with the diagnosis of systemic connective tissue disease in ANA test requested by a Rheumatology Unit. Samples of patients attended for the first time in the rheumatology unit, without prior ANA test, between January 2010 and December 2012 were selected. The dilution titers, immunofluorescence patterns and antigen specificity were recorded. In January 2015 the diagnosis of the patients were evaluated and classified in systemic disease connective tissue (systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, undifferentiated connective, antiphospholipid syndrome, mixed connective tissue and inflammatory myophaty) or not systemic disease connective tissue. A total of 1282 ANA tests requested by the Rheumatology Unit in subjects without previous study, 293 were positive, predominance of women (81.9%). Patients with systemic connective tissue disease were recorded 105, and 188 without systemic connective tissue disease. For 1/640 dilutions the positive predictive value in the connective was 73.3% compared to 26.6% of non-connective, and for values ≥1/1,280 85% versus 15% respectively. When performing the multivariate analysis we observed a positive association between 1/320 dilution OR 3.069 (95% CI: 1.237-7.614; P=.016), 1/640 OR 12.570 (95% CI: 3.659-43.187; P=.000) and ≥1/1,280 OR 42.136 (95% CI: 8.604-206.345; P=.000). These results show association titles dilution ≥1/320 in ANA's first test requested by a Rheumatology Unit with patients with systemic connective tissue disease. The VPP in these patients was higher than previous studies requested by other medical specialties. This may indicate the importance of application of the test in a targeted way. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Multifrequency ultrasound transducers for conformal interstitial thermal therapy.

PubMed

Chopra, Rajiv; Luginbuhl, Chris; Foster, F Stuart; Bronskill, Michael J

2003-07-01

Control over the pattern of thermal damage generated by interstitial ultrasound heating applicators can be enhanced by changing the ultrasound frequency during heating. The ability to change transmission frequency from a single transducer through the use of high impedance front layers was investigated in this study. The transmission spectrum of multifrequency transducers was calculated using the KLM equivalent circuit model and verified with experimental measurements on prototype transducers. The addition of a quarter-wavelength thick PZT (unpoled) front layer enabled the transmission of ultrasound at two discrete frequencies, 4.7 and 9.7 MHz, from a transducer with an original resonant frequency of 8.4 MHz. Three frequency transmission at 3.3, 8.4, and 10.8 MHz was possible for a transducer with a half-wavelength thick front layer. Calculations of the predicted thermal lesion size at each transmission frequency indicated that the depth of thermal lesion could be varied by a factor of 1.6 for the quarter-wavelength front layer. Heating experiments performed in excised liver tissue with a dual-frequency applicator confirmed this ability to control the shape of thermal lesions during heating to generate a desired geometry. Practical interstitial designs that enable the generation of shaped thermal lesions are feasible.

Predictive models for pressure-driven fluid infusions into brain parenchyma

NASA Astrophysics Data System (ADS)

Raghavan, Raghu; Brady, Martin

2011-10-01

Direct infusions into brain parenchyma of biological therapeutics for serious brain diseases have been, and are being, considered. However, individual brains, as well as distinct cytoarchitectural regions within brains, vary in their response to fluid flow and pressure. Further, the tissue responds dynamically to these stimuli, requiring a nonlinear treatment of equations that would describe fluid flow and drug transport in brain. We here report in detail on an individual-specific model and a comparison of its prediction with simulations for living porcine brains. Two critical features we introduced into our model—absent from previous ones, but requirements for any useful simulation—are the infusion-induced interstitial expansion and the backflow. These are significant determinants of the flow. Another feature of our treatment is the use of cross-property relations to obtain individual-specific parameters that are coefficients in the equations. The quantitative results are at least encouraging, showing a high fraction of overlap between the computed and measured volumes of distribution of a tracer molecule and are potentially clinically useful. Several improvements are called for; principally a treatment of the interstitial expansion more fundamentally based on poroelasticity and a better delineation of the diffusion tensor of a particle confined to the interstitial spaces.

Quantification and Comparison of Anti-Fibrotic Therapies by Polarized SRM and SHG-Based Morphometry in Rat UUO Model

PubMed Central

Weldon, Steve M.; Matera, Damian; Lee, ChungWein; Yang, Haichun; Fryer, Ryan M.; Fogo, Agnes B.; Reinhart, Glenn A.

2016-01-01

Renal interstitial fibrosis (IF) is an important pathologic manifestation of disease progression in a variety of chronic kidney diseases (CKD). However, the quantitative and reproducible analysis of IF remains a challenge, especially in experimental animal models of progressive IF. In this study, we compare traditional polarized Sirius Red morphometry (SRM) to novel Second Harmonic Generation (SHG)-based morphometry of unstained tissues for quantitative analysis of IF in the rat 5 day unilateral ureteral obstruction (UUO) model. To validate the specificity of SHG for detecting fibrillar collagen components in IF, co-localization studies for collagens type I, III, and IV were performed using IHC. In addition, we examined the correlation, dynamic range, sensitivity, and ability of polarized SRM and SHG-based morphometry to detect an anti-fibrotic effect of three different treatment regimens. Comparisons were made across three separate studies in which animals were treated with three mechanistically distinct pharmacologic agents: enalapril (ENA, 15, 30, 60 mg/kg), mycophenolate mofetil (MMF, 2, 20 mg/kg) or the connective tissue growth factor (CTGF) neutralizing antibody, EX75606 (1, 3, 10 mg/kg). Our results demonstrate a strong co-localization of the SHG signal with fibrillar collagens I and III but not non-fibrillar collagen IV. Quantitative IF, calculated as percent cortical area of fibrosis, demonstrated similar response profile for both polarized SRM and SHG-based morphometry. The two methodologies exhibited a strong correlation across all three pharmacology studies (r2 = 0.89–0.96). However, compared with polarized SRM, SHG-based morphometry delivered a greater dynamic range and absolute magnitude of reduction of IF after treatment. In summary, we demonstrate that SHG-based morphometry in unstained kidney tissues is comparable to polarized SRM for quantitation of fibrillar collagens, but with an enhanced sensitivity to detect treatment-induced reductions in IF. Thus, performing SHG-based morphometry on unstained kidney tissue is a reliable alternative to traditional polarized SRM for quantitative analysis of IF. PMID:27257917

Hi-tech of the prostate: interstitial laser coagulation of benign prostatic hypertrophy

NASA Astrophysics Data System (ADS)

Muschter, Rolf; Hofstetter, Alfons G.; Hessel, Stefan F. F.; Keiditsch, Ernst; Rothenberger, Karl-Heinz; Schneede, Peter; Frank, Klaus H.

1992-06-01

We report on the new technique of interstitial laser coagulation of the prostate (ILCP) in the treatment of benign prostatic hyperplasia (BPH). Basic experiments by use of a Nd:YAG laser in combination with a newly designed fiber tip homogeneously distributing the laser irradiation have been performed in potato, muscle, liver, and surgically removed human BPH-tissue to determine the volume of coagulation. The coagulation zone surrounding the probe was well defined and homogeneous. The size was dependent on laser power and irradiation time. Carbonization was never present except in darker tissues irradiated with high energy. Volume and time resolved measurements correlated well with the size of coagulation. 10 W and 5 minutes, for example, resulted in a coagulation zone of 17 X 15 mm. Comparable results have been seen in in-vivo experiments in surgically exposed canine prostates. Specimen for macroscopic and microscopic examination were taken immediately after treatment and after 5 and 35 days. The well demarked coagulation necrosis of the early stage resulted in cystic degeneration and fibrosis in the later stages. This was combined with shrinkage and reduction in volume. The urothelium of the urethra, the external sphincter and the rectum showed no damage. Until now, 15 patients suffering from obstructive symptoms due to BPH have been treated with interstitial laser coagulation. The probes were inserted from the perineum into the center of each lateral lobe of the prostate by transrectal ultrasound guidance, while the median lobe was treated by urethroscopic guidance, while the median lobe was treated by urethroscopic control. Dependent on the size of the prostate irradiation, time was 5 to 10 minutes per lobe at a power setting of 5 to 10 W.

Identification and characterization of VEGF and FGF from Hydra.

PubMed

Krishnapati, Lakshmi-Surekha; Ghaskadbi, Surendra

2013-01-01

Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) play important roles in the formation of the blood vascular system and in axon guidance, nervous system development and function. Here, we report isolation and characterization of VEGF and FGF homologues from Hydra vulgaris Ind-Pune, a Cnidarian which exhibits an organized nervous system and primitive epithelio-muscular cells. VEGF expression was prominent in the endoderm of the peduncle region and tentacles, as evident from in situ hybridization of whole polyps and its transverse sections. High levels of FGF were detected in the ectoderm of the budding region. The expression of VEGF in endodermal and FGF in interstitial cells was confirmed using sf-1 hydra, a temperature-sensitive mutant strain of Hydra magnipapillata. Tissue-specific expression of VEGF and FGF was confirmed by semi quantitative RT-PCR for ectodermal and endodermal tissues in H. vulgaris Ind-Pune. Treatment with SU5416, a specific inhibitor of the VEGF receptor, did not affect the whole polyp, but did delay both budding and head regeneration, suggesting a possible role of VEGF in nerve cell development, tube formation and/or in branching. FGF expression in the ectoderm of budding region, where the majority of interstitial stem cells reside suggests its role in interstitial stem cell maintenance. Further, activation of canonical Wnt signalling with the glycogen synthase kinase-3β (GSK-3β) inhibitor alsterpaullone caused down-regulation of VEGF and FGF, suggesting an antagonistic relationship between the Wnt and VEGF/FGF pathways. Our results indicate that VEGF and FGF evolved early in evolution, before the development of the blood vascular system, and open up the possibility of elucidating the evolutionarily ancient functions of VEGF and FGF.

Classification of interstitial lung disease patterns with topological texture features

NASA Astrophysics Data System (ADS)

Huber, Markus B.; Nagarajan, Mahesh; Leinsinger, Gerda; Ray, Lawrence A.; Wismüller, Axel

2010-03-01

Topological texture features were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honey-combing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. A set of 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and three Minkowski Functionals (MFs, e.g. MF.euler). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction. The best classification results were obtained by the MF features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers. The highest accuracy was found for MF.euler (97.5%, 96.6%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced topological texture features can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

High-dose-rate interstitial brachytherapy for the treatment of high-volume locally recurrent endometrial carcinoma.

PubMed

Huang, Kitty; D'Souza, David; Patil, Nikhilesh; Velker, Vikram; Leung, Eric; Stitt, Larry; Whiston, Frances; Sugimoto, Akira; McGee, Jacob; Prefontaine, Michel

2016-01-01

Limited therapeutic options are available for the treatment of locally recurrent endometrial carcinoma. Our objective was to report an institutional experience using interstitial brachytherapy (IBT) to treat significant recurrent endometrial carcinoma, including previously irradiated disease. Between December 2004 and September 2012, 40 patients with high-volume locally recurrent endometrial cancer were treated by high-dose-rate IBT (± external beam radiation therapy EBRT). Sixteen patients had prior radiotherapy: EBRT alone (n = 5), intracavitary brachytherapy alone (n = 3), or EBRT with intracavitary brachytherapy boost (n = 8). Actuarial outcome rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Median followup interval was 18 months. Median disease-free interval was 61 months. Actuarial local control, progression-free survival (PFS), and overall survival were 74% and 60%, 70% and 51%, and 83% and 72% at 12 and 24 months, respectively. p-Values for local control, progression-free survival, and overall survival between patient who had prior RT (n = 16) to no prior RT (n = 24) were p = 0.38, 0.32, and 0.90, respectively. Acute toxicities include Grade 1-2 pain (5%), genitourinary (7%), gastrointestinal (12%), soft tissue (5%), and dermatologic (12%). Four patients observed late Grade 3-4 toxicities, including rectal bleeding/fistula and soft tissue necrosis. High-dose-rate IBT is an effective treatment for locally recurrent endometrial carcinoma with an acceptable toxicity profile. Outcomes are similar between previously irradiated and nonirradiated patients. In women who have received prior radiotherapy and are often considered for palliative treatment, interstitial brachytherapy is a potentially curative option. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Accelerated partial breast irradiation: An analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wazer, David E.; Kaufman, Seth; Department of Radiation Oncology, Rhode Island Hospital, Brown University School of Medicine, Providence, RI

2006-02-01

Purpose: To perform a detailed analysis of variables associated with late tissue effects of high-dose-rate (HDR) interstitial brachytherapy accelerated partial breast irradiation (APBI) in a large cohort of patients with prolonged follow-up. Methods and Materials: Beginning in 1995, 75 women with Stage I/II breast cancer were enrolled in identical institutional trials evaluating APBI as monotherapy after lumpectomy. Patients eligible included those with T1-2, N0-1 ({<=}3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular nodal extension, and negative results on postexcision mammogram. All patients underwent surgical excision and postoperative irradiation with HDR interstitial brachytherapy. The planningmore » target volume was defined as the excision cavity plus a 2-cm margin. Treatment was delivered with a high-activity Ir-192 source at 3.4 Gy per fraction twice daily for 5 days to a total dose of 34 Gy. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. All patients were evaluated at 3-6-month intervals and assessed with a standardized cosmetic rating scale and according to Radiation Therapy Oncology Group late normal tissue toxicity scoring criteria. Clinical and therapy-related features were analyzed for their relationship to cosmetic outcome and toxicity rating. Clinical features analyzed included age, volume of resection, history of diabetes or hypertension, extent of axillary surgery, and systemic therapies. Therapy-related features analyzed included volume of tissue encompassed by the 100%, 150%, and 200% isodose lines (V100, V150, and V200, respectively), the dose homogeneity index (DHI), number of source dwell positions, and planar separation. Results: The median follow-up of all patients was 73 months (range, 43-118 months). The cosmetic outcome at last follow-up was rated as excellent, good, and fair/poor in 67%, 24%, and 9% of patients, respectively. Suboptimal cosmetic outcome was significantly associated with the number of source dwell positions, V150, and V200 and inversely associated with DHI (0.77 vs. 0.73; p = 0.05). Late skin toxicity was rated as Grade 0, 1, or 2 in 77%, 19%, and 4% of patients, respectively. The risk of Grade 1/2 skin toxicity was significantly associated with V150 and V200 and inversely associated with DHI (0.77 vs. 0.71; p = 0.009). Late subcutaneous toxicity was rated as Grade 0, 1, 2, 3, or 4 in 55%, 15%, 12%, 5%, and 13% of patients, respectively. The risk of Grade 0/1 vs. Grade 2-4 subcutaneous toxicity was significantly associated only with a lower value of DHI (0.77 vs. 0.73; p = 0.02). To further explore factors that might contribute to the risk of fat necrosis (symptomatic or asymptomatic), a separate analysis showed that only dose hotspots as reflected in V150 and V200 were significantly associated with elevated risk. The use of adriamycin-based chemotherapy after APBI was found to be associated with a significant increase in the incidence of higher-grade skin toxicity and a higher risk of fat necrosis and suboptimal cosmetic outcome. Patient age, volume of resection, extent of axillary surgery, a history of diabetes or hypertension, and the use of tamoxifen were not found to be significantly associated with cosmetic outcome or late normal tissue complications. Conclusions: Long-term cosmetic results and the risk of late skin and subcutaneous toxicity after APBI with interstitial HDR brachytherapy can be correlated with specific treatment-related variables. These data provide dosimetric parameters that might be used to minimize the risk of normal tissue injury after APBI interstitial brachytherapy.« less

Cellular control of connective tissue matrix tension.

PubMed

Langevin, Helene M; Nedergaard, Maiken; Howe, Alan K

2013-08-01

The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function, and cancer. Copyright © 2013 Wiley Periodicals, Inc.

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study

PubMed Central

Agarwal, Ashish; Gupta, Narinder Dev

2015-01-01

Background: Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. Materials and Methods: In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Results: Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Conclusion: Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch. PMID:26759591

[Nailfold capillaroscopy in the evaluation of Raynaud's phenomenon and undifferentiated connective tissue disease].

PubMed

Cortes, Sara; Clemente-Coelho, Paulo

2008-01-01

Microvascular abnormalities involved in the pathogenic mechanism of several connective tissue disorders can be detected by nailfold capillaroscopy. Evaluation of the interest of nailfold capillaroscopy results in patients with Raynaud s phenomenon or undifferentiated connective tissue disease and their correlation with diagnostic and therapeutical evolution. Selection of capillaroscopic and laboratory results of patients with the diagnosis of Raynaud s phenomenon (without defined connective tissue disease) or undifferentiated connective tissue disease. Evaluation of the present diagnosis and treatment comparing with the ones existed at the time of capillaroscopy performance. 80 patients were enrolled with an age of 51.4+/-14.3 years (mean+/-SD) 78 females (97.5%) with Raynaud s phenomenon and undifferentiated connective tissue disease 27 patients (33.8%); Raynaud s Phenomenon 46 patients (57.5%); undifferentiated connective tissue disease 7 patients (8.7%). The capillaroscopic results were normal 30 patients (37.5%); minor changes tortuosity enlargement 16 patients (20.0%) major changes 34 patients (42.5%) hemorrhages 25 patients (31.3%) megacapillaries 26 patients (32.5%) avascular areas 3 patients (3.8%). The introduction of new treatments after the capillaroscopy occurred in 32 patients (40.0%) and a new diagnosis was done in 39 patients (48.8%). Major changes in capillaroscopy correlated with the change of diagnosis and the introduction of a new treatment (p<0.0001). Nailfold capillaroscopy performed in patients with isolated Raynaud s phenomenon or undifferentiated connective tissue disease has a role in the prognostic evaluation related to the possibility of an evolution of the diagnosis or to the need of the introduction of new treatments.

Massive haemothorax after pulmonary endostapling preloaded with bioabsorbable tissue reinforcement material

PubMed Central

Kanai, Yoshihiko; Endo, Shunsuke; Tetsuka, Kenji; Yamamoto, Shinichi

2012-01-01

Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement. PMID:22184467

Massive haemothorax after pulmonary endostapling preloaded with bioabsorbable tissue reinforcement material.

PubMed

Kanai, Yoshihiko; Endo, Shunsuke; Tetsuka, Kenji; Yamamoto, Shinichi

2012-03-01

Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement.

[Persistent reddening and induration after wound cleansing with octenidine].

PubMed

Seegräber, M; T Ruzicka; Wollenberg, A

2017-04-01

With its long-lasting effectiveness, octenidine is an agent of first choice for antiseptic wound treatment. However, the manufacturer advises against instillation of the agent under pressure. A 50-year-old patient presented with erythema and extensive soft tissue induration after wound cleansing with octenidine under pressure. Due to the lack of resorption of the agent, this caused long-lasting interstitial soft tissue edema. This case demonstrates the importance of following the manufacturer's instructions for use. Advantages of the agent such as lack of systemic toxicity or broad spectrum efficacy can only be achieved if the agent is applied correctly.

Epigenetic regulation of cardiac fibrosis

PubMed Central

Stratton, Matthew S.; McKinsey, Timothy A.

2016-01-01

Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases. PMID:26876451

Stromal cells in tissue homeostasis: balancing regeneration and fibrosis.

PubMed

Rabelink, Ton J; Little, Melissa H

2013-12-01

The ageing population and the increasing prevalence of noncommunicable diseases such as diabetes and hypertension have led to an increased prevalence of chronic kidney disease. The generation of de novo kidney tissue from embryonic tissue and stem cells using tissue engineering approaches is being explored as an alternative to renal replacement therapy for treating the disease. It is, however, becoming clear that resident cells can not only induce fibrotic repair, but can also restore damaged kidney tissue. Mobilizing this innate capacity of the kidney to regenerate is of particular interest in the prevention of irreversible kidney failure. A novel concept is that the interaction of interstitial stromal cells with the local immune system may regulate tissue homeostasis and the balance between tissue repair and fibrosis. Mesenchymal stromal cells (MSCs), in particular, may enhance the intrinsic reparative capabilities of the kidney. This Perspectives article considers the innate regenerative potential of the kidney in the context of ongoing studies of MSC therapy.

[Phagocyte migration: an overview].

PubMed

Le Cabec, Véronique; Van Goethem, Emeline; Guiet, Romain; Maridonneau-Parini, Isabelle

2011-12-01

Phagocytes are the first line of host defense thanks to their capacity to infiltrate infected and wounded tissues, where they exert their bactericidal and tissue repair functions. However, tissue infiltration of phagocytes also stimulates the progression of pathologies such as cancer and chronic inflammatory diseases. It is therefore necessary to identify the molecular and cellular mechanisms that control this process to identify new therapeutic targets. Phagocytes leave the blood stream by crossing the vascular wall and infiltrate interstitial tissues, a three-dimensional environment. A state-of-the-art of the different steps of phagocyte tissue recruitment in vivo and of the different in vitro models is developed in this synthesis. We focus on recent data concerning the migration of phagocytes in three-dimensional environments. The use of two different migration modes, amoeboid and mesenchymal, by macrophages and the role of podosomes and proteases in the mesenchymal migration are discussed. © 2011 médecine/sciences – Inserm / SRMS.

Neurovascular manifestations of connective-tissue diseases: A review

PubMed Central

Kim, Sarasa T; Lanzino, Giuseppe; Kallmes, David F

2016-01-01

Patients with connective tissue diseases are thought to be at a higher risk for a number of cerebrovascular diseases such as intracranial aneurysms, dissections, and acute ischemic strokes. In this report, we aim to understand the prevalence and occurrences of such neurovascular manifestations in four heritable connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type 1, and Loeys-Dietz syndrome. We discuss the fact that although there are various case studies reporting neurovascular findings in these connective tissue diseases, there is a general lack of case-control and prospective studies investigating the true prevalence of these findings in these patient populations. Furthermore, the differences observed in the manifestations and histology of such disease pathologies encourages future multi-center registries and studies in better characterizing the pathophysiology, prevalence, and ideal treatment options of neurovascular lesions in patents with connective tissue diseases. PMID:27511817

[Feasibility of using connective tissue prosthesis for autoplastic repair of urinary bladder wall defects (an experimental study)].

PubMed

Tyumentseva, N V; Yushkov, B G; Medvedeva, S Y; Kovalenko, R Y; Uzbekov, O K; Zhuravlev, V N

2016-12-01

Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.

Comparative anatomy of the dorsal hump in mature Pacific salmon.

PubMed

Susuki, Kenta; Ban, Masatoshi; Ichimura, Masaki; Kudo, Hideaki

2017-07-01

Mature male Pacific salmon (Genus Oncorhynchus) demonstrate prominent morphological changes, such as the development of a dorsal hump. The degree of dorsal hump formation depends on the species in Pacific salmon. It is generally accepted that mature males of sockeye (O. nerka) and pink (O. gorbuscha) salmon develop most pronounced dorsal humps. The internal structure of the dorsal hump in pink salmon has been confirmed in detail. In this study, the dorsal hump morphologies were analyzed in four Pacific salmon species inhabiting Japan, masu (O. masou), sockeye, chum (O. keta), and pink salmon. The internal structure of the dorsal humps also depended on the species; sockeye and pink salmon showed conspicuous development of connective tissue and growth of bone tissues in the dorsal tissues. Masu and chum salmon exhibited less-pronounced increases in connective tissues and bone growth. Hyaluronic acid was clearly detected in dorsal hump connective tissue by histochemistry, except for in masu salmon. The lipid content in dorsal hump connective tissue was richer in masu and chum salmon than in sockeye and pink salmon. These results revealed that the patterns of dorsal hump formation differed among species, and especially sockeye and pink salmon develop pronounced dorsal humps through both increases in the amount of connective tissue and the growth of bone tissues. In contrast, masu and chum salmon develop their dorsal humps by the growth of bone tissues, rather than the development of connective tissue. © 2017 Wiley Periodicals, Inc.

Meat Science and Muscle Biology Symposium: manipulating meat tenderness by increasing the turnover of intramuscular connective tissue.

PubMed

Purslow, P P; Archile-Contreras, A C; Cha, M C

2012-03-01

Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the potential for manipulation of their connective tissue turnover.

Cone-Beam Computed Tomography Evaluation of Horizontal and Vertical Dimensional Changes in Buccal Peri-Implant Alveolar Bone and Soft Tissue: A 1-Year Prospective Clinical Study.

PubMed

Kaminaka, Akihiro; Nakano, Tamaki; Ono, Shinji; Kato, Tokinori; Yatani, Hirofumi

2015-10-01

This study evaluated changes in the horizontal and vertical dimensions of the buccal alveolar bone and soft tissue over a 1-year period following implant prosthesis. Thirty-three participants with no history of guided bone regeneration or soft tissue augmentation underwent dental implant placement with different types of connections. The dimensions of the buccal alveolar bone and soft tissue were evaluated immediately and at 1 year after prosthesis from reconstructions of cross-sectional cone-beam computed tomography images. The vertical and horizontal loss of buccal bone and soft tissue around implants with conical connections were lower than around those with external or internal connections. Statistically significant negative correlations were observed between initial horizontal bone thickness and changes in vertical bone and soft tissue height (p < .05), and between initial horizontal soft tissue thickness and the change in vertical soft tissue height (p < .05). Implants with a conical connection preserve peri-implant alveolar bone and soft tissue more effectively than other connection types. Furthermore, the initial buccal alveolar bone and soft tissue thickness around the implant platform may influence their vertical dimensional changes at 1 year after implant prosthesis. © 2014 Wiley Periodicals, Inc.

In vitro osteosarcoma biosensing using THz time domain spectroscopy

NASA Astrophysics Data System (ADS)

Ferguson, Bradley S.; Liu, Haibo; Hay, Shelley; Findlay, David; Zhang, Xi-Cheng; Abbott, Derek

2004-03-01

Terahertz time domain spectroscopy (THz-TDS) has a wide range of applications from semiconductor diagnostics to biosensing. Recent attention has focused on bio-applications and several groups have noted the ability of THz-TDS to differentiate basal cell carcinoma tissue from healthy dermal tissue ex vivo. The contrast mechanism is unclear but has been attributed to increased interstitial water in cancerous tissue. In this work we investigate the THz response of human osteosarcoma cells and normal human bone cells grown in culture to isolate the cells' responses from other effects. A classification algorithms based on a frequency selection by genetic algorithm is used to attempt to differentiate between the cell types based on the THz spectra. Encouraging preliminary results have been obtained.

Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.

PubMed

Love, Ryan J; Jones, Kim S

2013-12-01

Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Immediate placement and provisionalization of maxillary anterior single implant with guided bone regeneration, connective tissue graft, and coronally positioned flap procedures.

PubMed

Waki, Tomonori; Kan, Joseph Y K

2016-01-01

Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations.

The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial.

PubMed

Dowman, Leona M; McDonald, Christine F; Hill, Catherine J; Lee, Annemarie L; Barker, Kathryn; Boote, Claire; Glaspole, Ian; Goh, Nicole S L; Southcott, Anne M; Burge, Angela T; Gillies, Rebecca; Martin, Alicia; Holland, Anne E

2017-07-01

Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs). To establish the impact of exercise training in patients with ILDs of differing aetiology and severity. 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care. Six-minute walk distance (6MWD), Chronic Respiratory Disease Questionnaire (CRDQ), St George Respiratory Questionnaire IPF-specific version (SGRQ-I) and modified Medical Research Council dyspnoea score were measured at baseline, 9 weeks and 6 months. Exercise training significantly increased 6MWD (25 m, 95% CI 2 to 47 m) and health-related quality of life (CRDQ and SGRQ-I) in people with ILD. Larger improvements in 6MWD, CRDQ, SGRQ-I and dyspnoea occurred in asbestosis and IPF compared with CTD-ILD, but with few significant differences between subgroups. Benefits declined at 6 months except in CTD-ILD. Lower baseline 6MWD and worse baseline symptoms were associated with greater benefit in 6MWD and symptoms following training. Greater gains were seen in those whose exercise prescription was successfully progressed according to the protocol. At 6 months, sustained improvements in 6MWD and symptoms were associated with better baseline lung function and less pulmonary hypertension. Exercise training is effective in patients across the range of ILDs, with clinically meaningful benefits in asbestosis and IPF. Successful exercise progression maximises improvements and sustained treatment effects favour those with milder disease. Results, ACTRN12611000416998. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

CT guided interstitial therapy of pancreatic carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haaga, J.R.; Owens, D.B.; Kellermeyer, R.W.

1987-11-01

We describe the use of percutaneous CT guidance for localization and placement of /sup 192/Ir sources into a patient with pancreatic carcinoma. We have shown the feasibility of this procedure and the lack of complications which are probably due to minimal damage to tissue involved. Computed tomography is ideally suited for percutaneous implantation because it provides the most accurate method for needle placement within the abdomen.

Micromechanics and constitutive modeling of connective soft tissues.

PubMed

Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

2016-07-01

In this paper, a micromechanical model for connective soft tissues based on the available histological evidences is developed. The proposed model constituents i.e. collagen fibers and ground matrix are considered as hyperelastic materials. The matrix material is assumed to be isotropic Neo-Hookean while the collagen fibers are considered to be transversely isotropic hyperelastic. In order to take into account the effects of tissue structure in lower scales on the macroscopic behavior of tissue, a strain energy density function (SEDF) is developed for collagen fibers based on tissue hierarchical structure. Macroscopic response and properties of tissue are obtained using the numerical homogenization method with the help of ABAQUS software. The periodic boundary conditions and the proposed constitutive models are implemented into ABAQUS using the DISP and the UMAT subroutines, respectively. The existence of the solution and stable material behavior of proposed constitutive model for collagen fibers are investigated based on the poly-convexity condition. Results of the presented micromechanics model for connective tissues are compared and validated with available experimental data. Effects of geometrical and material parameters variation at microscale on macroscopic mechanical behavior of tissues are investigated. The results show that decrease in collagen content of the connective tissues like the tendon due to diseases leads 20% more stretch than healthy tissue under the same load which can results in connective tissue malfunction and hypermobility in joints. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dicarbonyl stress in clinical obesity.

PubMed

Masania, Jinit; Malczewska-Malec, Malgorzata; Razny, Urszula; Goralska, Joanna; Zdzienicka, Anna; Kiec-Wilk, Beata; Gruca, Anna; Stancel-Mozwillo, Julita; Dembinska-Kiec, Aldona; Rabbani, Naila; Thornalley, Paul J

2016-08-01

The glyoxalase system in the cytoplasm of cells provides the primary defence against glycation by methylglyoxal catalysing its metabolism to D-lactate. Methylglyoxal is the precursor of the major quantitative advanced glycation endproducts in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. Glyoxalase 1 of the glyoxalase system was linked to anthropometric measurements of obesity in human subjects and to body weight in strains of mice. Recent conference reports described increased weight gain on high fat diet-fed mouse with lifelong deficiency of glyoxalase 1 deficiency, compared to wild-type controls, and decreased weight gain in glyoxalase 1-overexpressing transgenic mice, suggesting a functional role of glyoxalase 1 and dicarbonyl stress in obesity. Increased methylglyoxal, dicarbonyl stress, in white adipose tissue and liver may be a mediator of obesity and insulin resistance and thereby a risk factor for development of type 2 diabetes and non-alcoholic fatty liver disease. Increased methylglyoxal formation from glyceroneogenesis on adipose tissue and liver and decreased glyoxalase 1 activity in obesity likely drives dicarbonyl stress in white adipose tissue increasing the dicarbonyl proteome and related dysfunction. The clinical significance will likely emerge from on-going clinical evaluation of inducers of glyoxalase 1 expression in overweight and obese subjects. Increased transcapillary escape rate of albumin and increased total body interstitial fluid volume in obesity likely makes levels of glycation of plasma protein unreliable indicators of glycation status in obesity as there is a shift of albumin dwell time from plasma to interstitial fluid, which decreases overall glycation for a given glycemic exposure.

Skeletal muscle-derived interstitial progenitor cells (PICs) display stem cell properties, being clonogenic, self-renewing, and multi-potent in vitro and in vivo.

PubMed

Cottle, Beverley J; Lewis, Fiona C; Shone, Victoria; Ellison-Hughes, Georgina M

2017-07-04

The development of cellular therapies to treat muscle wastage with disease or age is paramount. Resident muscle satellite cells are not currently regarded as a viable cell source due to their limited migration and growth capability ex vivo. This study investigated the potential of muscle-derived PW1 + /Pax7 - interstitial progenitor cells (PICs) as a source of tissue-specific stem/progenitor cells with stem cell properties and multipotency. Sca-1 + /PW1 + PICs were identified on tissue sections from hind limb muscle of 21-day-old mice, isolated by magnetic-activated cell sorting (MACS) technology and their phenotype and characteristics assessed over time in culture. Green fluorescent protein (GFP)-labelled PICs were used to determine multipotency in vivo in a tumour formation assay. Isolated PICs expressed markers of pluripotency (Oct3/4, Sox2, and Nanog), were clonogenic, and self-renewing with >60 population doublings, and a population doubling time of 15.8 ± 2.9 h. PICs demonstrated an ability to generate both striated and smooth muscle, whilst also displaying the potential to differentiate into cell types of the three germ layers both in vitro and in vivo. Moreover, PICs did not form tumours in vivo. These findings open new avenues for a variety of solid tissue engineering and regeneration approaches, utilising a single multipotent stem cell type isolated from an easily accessible source such as skeletal muscle.

Bang-bang Model for Regulation of Local Blood Flow

PubMed Central

Golub, Aleksander S.; Pittman, Roland N.

2013-01-01

The classical model of metabolic regulation of blood flow in muscle tissue implies the maintenance of basal tone in arterioles of resting muscle and their dilation in response to exercise and/or tissue hypoxia via the evoked production of vasodilator metabolites by myocytes. A century-long effort to identify specific metabolites responsible for explaining active and reactive hyperemia has not been successful. Furthermore, the metabolic theory is not compatible with new knowledge on the role of physiological radicals (e.g., nitric oxide, NO, and superoxide anion, O2−) in the regulation of microvascular tone. We propose a model of regulation in which muscle contraction and active hyperemia are considered the physiologically normal state. We employ the “bang-bang” or “on/off” regulatory model which makes use of a threshold and hysteresis; a float valve to control the water level in a tank is a common example of this type of regulation. Active bang-bang regulation comes into effect when the supply of oxygen and glucose exceeds the demand, leading to activation of membrane NADPH oxidase, release of O2− into the interstitial space and subsequent neutralization of the interstitial NO. Switching arterioles on/off when local blood flow crosses the threshold is realized by a local cell circuit with the properties of a bang-bang controller, determined by its threshold, hysteresis and dead-band. This model provides a clear and unambiguous interpretation of the mechanism to balance tissue demand with a sufficient supply of nutrients and oxygen. PMID:23441827

Low-power interstitial photocoagulation of uterine leiomyomas by KTP/YAG laser: a review of 50 consecutive cases

NASA Astrophysics Data System (ADS)

Chapman, Roxana

1994-12-01

Interstitial laser photocoagulation (ILP), which is a new method of low power laser destruction of tumors, has been used to treat laparoscopically 50 consecutive patients with symptomatic uterine leiomyomas which were difficult or impossible to remove via laparoscopy. The KTP/YAG laser, with wavelengths of 532 and 1064 nm respectively, was employed. Holes 2 cm apart were drilled with a 600 micrometers quartz laser fiber employing the KTP component at 8 W and subsequent coagulation of the surrounding myoma tissue was accomplished during the withdrawal of the fiber over the course of 10 - 30 s but using the YAG component at 8 W until the whole myoma had been treated. Thirty seven became symptom free and have remained so. Six were lost to follow up. Of 10 complaining of subfertility 4, in whom uterine myomas were the only etiological factor, have become pregnant. Seven patients required further treatment: Two were retreated because their myomas were excessively large and did not completely disappear with the initial ILP, 2 received further ILP because of the development of new myomas and 3 were subjected to laparoscopically assisted vaginal hysterectomy at patients' request (2 because of the development of new myomas and 1 because of the development of further endometriosis). Finally, in 7 cases, residual tumor or scar tissue was biopsied and examined for the presence of oestrogen and progesterone receptors. None was discovered and in 2 subsequent pregnancy did not cause further growth of residual myoma tissue.

Active tissue stiffness modulation controls valve interstitial cell phenotype and osteogenic potential in 3D culture.

PubMed

Duan, Bin; Yin, Ziying; Hockaday Kang, Laura; Magin, Richard L; Butcher, Jonathan T

2016-05-01

Calcific aortic valve disease (CAVD) progression is a highly dynamic process whereby normally fibroblastic valve interstitial cells (VIC) undergo osteogenic differentiation, maladaptive extracellular matrix (ECM) composition, structural remodeling, and tissue matrix stiffening. However, how VIC with different phenotypes dynamically affect matrix properties and how the altered matrix further affects VIC phenotypes in response to physiological and pathological conditions have not yet been determined. In this study, we develop 3D hydrogels with tunable matrix stiffness to investigate the dynamic interplay between VIC phenotypes and matrix biomechanics. We find that VIC populated within hydrogels with valve leaflet like stiffness differentiate towards myofibroblasts in osteogenic media, but surprisingly undergo osteogenic differentiation when cultured within lower initial stiffness hydrogels. VIC differentiation progressively stiffens the hydrogel microenvironment, which further upregulates both early and late osteogenic markers. These findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification. Temporal stiffening of pathologically lower stiffness matrix back to normal level, or blocking the mechanosensitive RhoA/ROCK signaling pathway, delays the osteogenic differentiation process. Therefore, direct ECM biomechanical modulation can affect VIC phenotypes towards and against osteogenic differentiation in 3D culture. These findings highlight the importance of the homeostatic maintenance of matrix stiffness to restrict pathological VIC differentiation. We implement 3D hydrogels with tunable matrix stiffness to investigate the dynamic interaction between valve interstitial cells (VIC, major cell population in heart valve) and matrix biomechanics. This work focuses on how human VIC responses to changing 3D culture environments. Our findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification, which is the hallmark of calcific aortic valve disease. Temporal stiffening of pathologically lower stiffness matrix back to normal level, or blocking the mechanosensitive signaling pathway, delays VIC osteogenic differentiation. Our findings provide an improved understanding of VIC-matrix interactions to aid in interpretation of VIC calcification studies in vitro and suggest that ECM disruption resulting in local tissue stiffness decreases may promote calcific aortic valve disease. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Identifying the architecture of a supracellular actomyosin network that induces tissue folding

NASA Astrophysics Data System (ADS)

Yevick, Hannah; Stoop, Norbert; Dunkel, Jorn; Martin, Adam

During embryonic development, the establishment of correct tissue form ensures proper tissue function. Yet, how the thousands of cells within a tissue coordinate force production to sculpt tissue shape is poorly understood. One important tissue shape change is tissue folding where a cell sheet bends to form a closed tube. Drosophila (fruit fly) embryos undergo such a folding event, called ventral furrow formation. The ventral furrow is associated with a supracellular network of actin and myosin, where actin-myosin fibers assemble and connect between cells. It is not known how this tissue-wide network grows and connects over time, how reproducible it is between embryos, and what determines its architecture. Here, we used topological feature analysis to quantitatively and dynamically map the connections and architecture of this supracellular network across hundreds of cells in the folding tissue. We identified the importance of the cell unit in setting up the tissue-scale architecture of the network. Our mathematical framework allows us to explore stereotypic properties of the myosin network such that we can investigate the reproducibility of mechanical connections for a morphogenetic process. NIH F32.

Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

PubMed Central

Murthy, S.; Gautam, M. K.; Goel, Shalini; Purohit, V.; Sharma, H.; Goel, R. K.

2013-01-01

Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology (dead space wound). BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity. PMID:23984424

Evaluation of in vivo wound healing activity of Bacopa monniera on different wound model in rats.

PubMed

Murthy, S; Gautam, M K; Goel, Shalini; Purohit, V; Sharma, H; Goel, R K

2013-01-01

Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology (dead space wound). BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity.

Efficacy of Connective Tissue with and without Periosteum in Regeneration of Intrabony Defects

PubMed Central

Esfahanian, Vahid; Golestaneh, Hedayatollah; Moghaddas, Omid; Ghafari, Mohammad Reza

2014-01-01

Background and aims. Connective tissue grafts with and without periosteum is used in regenerative treatments of bone and has demonstrated successful outcomes in previous investigations. The aim of present study was to evaluate the effectiveness of connective tissue graft with and without periosteum in regeneration of intrabony defects. Materials and methods. In this single-blind randomized split-mouth clinical trial, 15 pairs of intrabony defects in 15 patients with moderate to advanced periodontitis were treated by periosteal connective tissue graft + ABBM (test group) or non-periosteal connective tissue graft + ABBM (control group). Probing pocket depth, clinical attachment level, free gingival margin position, bone crestal position, crest defect depth and defect depth to stent were measured at baseline and after six months by surgical re-entry. Data was analyzed by Student’s t-test and paired t-tests (α=0.05). Results. Changes in clinical parameters after 6 months in the test and control groups were as follows: mean of PPD reduction: 3.1±0.6 (P<0.0001); 2.5±1.0 mm (P<0.0001), CAL gain: 2.3±0.9 (P<0.0001); 2.2±1.0 mm (P<0.0001), bone fill: 2.2±0.7 mm (P<0.0001); 2.2±0.7 mm (P<0.0001), respectively. No significant differences in the position of free gingival margin were observed during 6 months compared to baseline in both groups. Conclusion. Combinations of periosteal connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM were similarly effective in treating intrabony defects without any favor for any group. Connective tissue and perio-steum can be equally effective in regeneration of intrabony defects. PMID:25587379

Estimating the incidence of connective tissue diseases and vasculitides in a defined population in Northern Savo area in 2010.

PubMed

Elfving, P; Marjoniemi, O; Niinisalo, H; Kononoff, A; Arstila, L; Savolainen, E; Rutanen, J; Kaipiainen-Seppänen, O

2016-07-01

Objective of the study was to evaluate the annual incidence and distribution of autoimmune connective tissue diseases and vasculitides during 2010. All units practicing rheumatology in the Northern Savo area, Finland, participated in the study by collecting data on newly diagnosed adult patients with autoimmune connective tissue disease or vasculitis over 1-year period. Seventy-two cases with autoimmune connective tissue disease were identified. The annual incidence rates were as follows: systemic lupus erythematosus 3.4/100,000 (95 % CI 1.4-7.0), idiopathic inflammatory myopathies 1.9 (0.5-5.0), systemic sclerosis 4.4 (2.0-8.3), mixed connective tissue disease 1.0 (0.1-3.5), Sjögren's syndrome 10.7 (6.7-16.1) and undifferentiated connective tissue disease 13.6 (9.0-19.6). The annual incidence rates among vasculitis category were as follows: antineutrophil cytoplasmic antibody-associated vasculitis 1.5/100,000 (95 % CI 0.3-4.3), central nervous system vasculitis 0.5 (0-2.7) and Henoch-Schönlein purpura 1.5 (0.3-4.3). The annual incidence of giant cell arteritis in the age group of 50 years or older was 7.5/100,000 (95 % CI 3.2-14.8). The longest delay from symptom onset to diagnosis occurred in systemic sclerosis. The incidences of autoimmune connective tissue diseases and vasculitides were comparable with those in published literature. The present study showed female predominance in all connective tissue diseases, excluding idiopathic inflammatory muscle diseases and mean age at onset of disease around 50 years of age. Despite improved diagnostic tools, diagnostic delay is long especially among patients with systemic sclerosis.

Morphology of the lingual papillae in the fishing cat.

PubMed

Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

2014-01-01

We examined the dorsal lingual surface of an adult fishing cat (Prionailurus viverrinus) by scanning electron microscopy. The filiform papillae on the lingual apex had several pointed processes. The connective tissue core of the filiform papillae resembleda a well in shape. The filiform papillae on the anterior part of the lingual body were large and cylindrical in shape. The connective tissue core of the filiform papillae consisted of a large conical papilla. The filiform papillae on the central part of the lingual body were large and conical. The connective tissue core of the filiform papillae consisted of a large main process and some secondary processes. The connective tissue core of the fungiform papillae did not have processes. The vallate papillae were surrounded by a groove and a pad. The top of the connective tissue core of the vallate papillae had a rough surface with no spines.

Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

PubMed Central

Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.

2015-01-01

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

Investigation of interstitial ultrasound ablation of spinal and paraspinal tumors: A patient-specific and parametric simulation study

NASA Astrophysics Data System (ADS)

Scott, Serena J.; Salgaonkar, Vasant; Prakash, Punit; Burdette, E. Clif; Diederich, Chris J.

2017-03-01

Preferential acoustic absorption and heating of bone can significantly impact interstitial ultrasound ablation of tumors within or bordering the spine. Furthermore, intervening cortical bone may provide acoustic and thermal insulation that can protect sensitive structures nearby, such as the spinal cord. The objectives of this study are firstly, to apply parametric and patient-specific models to theoretically assess the feasibility of interstitial ultrasound ablation of tumors within and near the spine, and secondly, to identify potential energy delivery strategies, safety criteria, advantages, and disadvantages of interstitial ultrasound in this setting. Transient biothermal models using previously validated approximations for power deposition within bone from interstitial sources were employed. Multilayered axisymmetric models were used to perform a parametric assessment of the impact of tumor dimensions, attenuation (dependent on residual bone content), perfusion, and maximum temperature thresholds on necessary treatment parameters and on treatment effectiveness. 3D patient-specific finite element models were generated based on segmented CT scans for nine representative patient cases selected to bracket a range of clinical interest, with tumors in or near the vertebrae, sacrum, and ilium. Tumors were 10-27 mm in diameter, 10-43 mm long, and 0-14 mm from the spinal canal. Paraspinal tumors, osteolytic vertebral tumors, and a mixed osteolytic/osteoblastic iliac bone tumor were considered. 7 MHz (1.5 mm OD) and 3.0 MHz (3.2 mm OD) applicators with an array of 1-4 tubular transducers (0.5 -1.5 cm long, 150-360° sector angles), were applied in various implant configurations. Variable thicknesses of bone insulating critical anatomy from the tumor and insulation of the spinal cord with injected carbon dioxide were also investigated for definition of safety margins and possible protection of critical structures. 6-44 mm diameter osteolytic tumors surrounded by bone and blastic (high bone content) lesions up to 20 mm in diameter could be fully ablated by 7 MHz interstitial ultrasound using 120-5,900 J and treatment durations of 0.4-15 min. 100% of the volumes of five simulated tumors located 4.3-14 mm from the spinal canal and 94.6-99.9% of the volumes of four simulated tumors 0-4.5 mm from the spinal canal were ablated (>240 EM43°C) within 15 min without damaging (<6 EM43°C) critical nerves. Preferential ultrasound absorption and concomitant heating at bone surfaces allowed for faster, more effective ablations with less delivered energy. 3-5 mm of normal cortical bone was found to provide a safety margin and reduce temperature elevations in untargeted tissues. Critical anatomy less than 3-5 mm from a tumor encapsulated by bone could be preserved by reducing the acoustic energy aimed towards these structures and/or through injection of insulating CO2. Parametric and patient-specific studies demonstrated the feasibility of interstitial ultrasound ablation of paraspinal tumors and osteolytic tumors within the spine. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in highly osteolytic and soft tissue tumors in and near bone compared to other heating modalities. This work was supported by the NIH grant R44CA112852.

Immunohistochemical and morphometric evaluation of COX-1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis* ,**

PubMed Central

Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza

2013-01-01

OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763

In situ temperature measurements with thermocouple probes during laser interstitial thermotherapy (LITT): quantification and correction of a measurement artifact.

PubMed

Manns, F; Milne, P J; Gonzalez-Cirre, X; Denham, D B; Parel, J M; Robinson, D S

1998-01-01

The purpose of this work was to quantify the magnitude of an artifact induced by stainless steel thermocouple probes in temperature measurements made in situ during experimental laser interstitial thermo-therapy (LITT). A procedure for correction of this observational error is outlined. A CW Nd:YAG laser system emitting 20W for 25-30 s delivered through a fiber-optic probe was used to create localized heating. The temperature field around the fiber-optic probe during laser irradiation was measured every 0.3 s in air, water, 0.4% intralipid solution, and fatty cadaver pig tissue, with a field of up to fifteen needle thermocouple probes. Direct absorption of Nd:YAG laser radiation by the thermocouple probes induced an overestimation of the temperature, ranging from 1.8 degrees C to 118.6 degrees C in air, 2.2 degrees C to 9.9 degrees C in water, 0.7 C to 4.7 C in intralipid and 0.3 C to 17.9 C in porcine tissue after irradiation at 20W for 30 s and depending on the thermocouple location. The artifact in porcine tissue was removed by applying exponential and linear fits to the measured temperature curves. Light absorption by thermocouple probes can induce a significant artifact in the measurement of laser-induced temperature increases. When the time constant of the thermocouple effect is much smaller than the thermal relaxation time of the surrounding tissue, the artifact can be accurately quantified. During LITT experiments where temperature differences of a few degrees are significant, the thermocouple artifact must be removed in order to be able accurately to predict the treatment outcome.

Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

PubMed

Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

2017-09-01

Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

[CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

PubMed

Madiyeva, M; Rymbayeva, T

2017-11-01

The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

Connective tissue fibroblasts and Tcf4 regulate myogenesis

PubMed Central

Mathew, Sam J.; Hansen, Jody M.; Merrell, Allyson J.; Murphy, Malea M.; Lawson, Jennifer A.; Hutcheson, David A.; Hansen, Mark S.; Angus-Hill, Melinda; Kardon, Gabrielle

2011-01-01

Muscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4GFPCre mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis. PMID:21177349

Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

PubMed Central

Roberts, Michael D.; Grau, Vicente; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony J.; Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage. PMID:18806292

Toll-Like Receptor Signaling and SIGIRR in Renal Fibrosis upon Unilateral Ureteral Obstruction

PubMed Central

Allam, Ramanjaneyulu; Ryu, Mi; Clauss, Sebastian; Susanti, Heni Eka; Römmele, Christoph; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

2011-01-01

Innate immune activation via IL-1R or Toll-like receptors (TLR) contibutes to acute kidney injury but its role in tissue remodeling during chronic kidney disease is unclear. SIGIRR is an inhibitor of TLR-induced cytokine and chemokine expression in intrarenal immune cells, therefore, we hypothesized that Sigirr-deficiency would aggravate postobstructive renal fibrosis. The expression of TLRs as well as endogenous TLR agonists increased within six days after UUO in obstructed compared to unobstructed kidneys while SIGIRR itself was downregulated by day 10. However, lack of SIGIRR did not affect the intrarenal mRNA expression of proinflammatory and profibrotic mediators as well as the numbers of intrarenal macrophages and T cells or morphometric markers of tubular atrophy and interstitial fibrosis. Because SIGIRR is known to block TLR/IL-1R signaling at the level of the intracellular adaptor molecule MyD88 UUO experiments were also performed in mice deficient for either MyD88, TLR2 or TLR9. After UUO there was no significant change of tubular interstitial damage and interstitial fibrosis in neither of these mice compared to wildtype counterparts. Additional in-vitro studies with CD90+ renal fibroblasts revealed that TLR agonists induce the expression of IL-6 and MCP-1/CCL2 but not of TGF-β, collagen-1α or smooth muscle actin. Together, postobstructive renal interstitial fibrosis and tubular atrophy develop independent of SIGIRR, TLR2, TLR9, and MyD88. These data argue against a significant role of these molecules in renal fibrosis. PMID:21544241

Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases

PubMed Central

Meng, Peng; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

2016-01-01

Background Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. Methods In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients’ final diagnoses based on multi-disciplinary consensus. Results One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24–79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Conclusions Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited. PMID:28149543

Interstitial devices for treating deep seated tumors

NASA Astrophysics Data System (ADS)

Lafon, Cyril; Cathignol, Dominique; Prat, Frédéric; Melodelima, David; Salomir, Rares; Theillère, Yves; Chapelon, Jean-Yves

2006-05-01

Techniques using intracavitary or interstitial applicators have been proposed because extracorporeal HIFU techniques are not always suitable for deep-seated tumors. Bones or gaseous pockets may indeed be located in the intervening tissue. The objective is to bring the ultrasound source as close as possible to the target through natural routes in order to minimize the effects of attenuation and phase aberration along the ultrasound pathway. Under these circumstances, it becomes possible to use higher frequency, thus increasing the ultrasonic absorption coefficient and resulting in more efficient heating of the treatment region. In contrast to extra-corporeal applicators, the design of interstitial probes imposes additional constraints relative to size and ergonomy. The goal of this paper is to present the range of miniature interstitial applicators we developed at INSERM for various applications. The sources are rotating plane water-cooled transducers that operate at a frequency between 3 and 10 MHz depending on the desired therapeutic depth. The choice of a plane transducer rather than divergent sources permits to extend the therapeutic depth and to enhance the angular selectivity of the treatment Rotating single element flat transducer can also be replaced by cylindrical arrays for rotating electronically a reconstructed plane wave. When extended zone of coagulation are required, original therapeutic modalities combining cavitation and thermal effects are used. These methods consist in favoring in depth heating by increasing the acoustic attenuation away from the transducer with the presence of bubbles. When associated to modern imaging modalities, these minimally invasive therapeutic devices offer very promising options for cancer treatment. For examples, two versions of an image-guided esophageal applicator are designed: one uses a retractable ultrasound mini probe for the positioning of the applicator, while the other is MRI compatible and offers on line monitoring of temperature. Beyond these engineering considerations, our clinical experience demonstrates that following interstitial routes for applying HIFU is an interesting therapeutic option when targeted sites cannot be reached from outside the patient.

Connective Tissue Characteristics around Healing Abutments of Different Geometries: New Methodological Technique under Circularly Polarized Light.

PubMed

Delgado-Ruiz, Rafael Arcesio; Calvo-Guirado, Jose Luis; Abboud, Marcus; Ramirez-Fernandez, Maria Piedad; Maté-Sánchez de Val, José Eduardo; Negri, Bruno; Gomez-Moreno, Gerardo; Markovic, Aleksa

2015-08-01

To describe contact, thickness, density, and orientation of connective tissue fibers around healing abutments of different geometries by means of a new method using coordinates. Following the bilateral extraction of mandibular premolars (P2, P3, and P4) from six fox hound dogs and a 2-month healing period, 36 titanium implants were inserted, onto which two groups of healing abutments of different geometry were screwed: Group A (concave abutments) and Group B (wider healing abutment). After 3 months the animals were sacrificed and samples extracted containing each implant and surrounding soft and hard tissues. Histological analysis was performed without decalcifying the samples by means of circularly polarized light under optical microscope and a system of vertical and horizontal coordinates across all the connective tissue in an area delimited by the implant/abutment, epithelium, and bone tissue. In no case had the connective tissue formed a connection to the healing abutment/implant in the internal zone; a space of 35 ± 10 μm separated the connective tissue fibers from the healing abutment surface. The total thickness of connective tissue in the horizontal direction was significantly greater in the medial zone in Group B than in Group A (p < .05). The orientation of the fibers varied according to the coordinate area so that internal coordinates showed a higher percentage of parallel fibers in Group A (p < .05) and a higher percentage of oblique fibers in Group B (p < .05); medial coordinates showed more oblique fibers (p < .05); and the area of external coordinates showed the highest percentage of perpendicular fibers (p < .05). The fiber density was higher in the basal and medial areas (p < .05). Abutment geometry influences the orientation of collagen fibers; therefore, an abutment with a profile wider than the implant platform favors oblique and perpendicular orientation of collagen fibers and greater connective tissue thickness. © 2013 Wiley Periodicals, Inc.

[50 years of connective tissue research: from the French Connective Tissue Club to the French Society of Extracellular Matrix Biology].

PubMed

Maquart, François-Xavier; Borel, Jacques-Paul

2012-01-01

The history of connective tissue research began in the late 18th century. However, it is only 50 years later that the concept of connective tissue was shaped. It took another fifty years before biochemical knowledge of extracellular matrix macromolecules began to emerge in the first half of the 20th century. In 1962, thanks to Ladislas and Barbara Robert, back from the US, the first society called "French Connective Tissue Club" was created in Paris. The first board was constituted of Albert Delaunay, Suzanne Bazin and Ladislas Robert. Very quickly, under the influence of these pioneers, national and international meetings were organized and, in 1967, a "Federation of the European Connective Tissue Clubs" was created at the initiative of Ladislas Robert (Paris) and John Scott (Manchester). It spread rapidly to the major European nations. In 1982 the transformation of "Clubs" in "Societies" occurred, a name more in line with the requirements of the time. In 2008, the "French Connective Tissue Society" became the "French Society of Extracellular Matrix Biology" ("Société Française de Biologie de la Matrice Extracellulaire", SFBMEc), to better highlight the importance of the extracellular matrix in the biology of living organisms. The SFBMEc's mission today is to promote and develop scientific exchanges between academic, industrial, and hospital laboratories involved in research on the extracellular matrix. SFBMEc organizes or subsidizes scientific meetings and awards scholarships to Ph.D. students or post-docs to participate in international conferences. It includes 200 to 250 members from different disciplines, developing strong interactions between scientists, clinicians and pathologists. It is present all around the French territory in many research laboratories. During these last 50 years, the extraordinary advances made possible by the development of new investigation techniques, in particular molecular biology, cell and tissue imaging, molecular modeling, etc., have permitted a considerable increase of the knowledge in the field of connective tissue. © Société de Biologie, 2012.

Tissue mechanics regulate brain development, homeostasis and disease

PubMed Central

Barnes, J. Matthew

2017-01-01

ABSTRACT All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells – for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer. PMID:28043968

Necrotizing crescentic glomerulonephritis related to sarcoidosis: a case report.

PubMed

Maroz, Natallia; Field, Halle

2015-12-14

Renal injury due to sarcoidosis develops in less than a quarter of patients with this systemic disease. In most cases, granulomatous tissue alters the production of vitamin D, which leads to hypercalciuria, nephrocalcinosis, and nephrolithiasis. Granulomatous interstitial nephritis is another well-recognized pathological process associated with sarcoidosis. However, a glomerular pathology is very rarely noted, and only a few cases are reported to have cellular crescentic glomerulonephritis. We describe the case of a 26-year-old African American woman with systemic sarcoidosis, with a unique constellation of renal lesions, including noncaseating epithelioid granulomatous necrotizing interstitial nephritis, cellular crescent formation, and necrotizing vasculitis. Immunosuppressive therapy was helpful for alleviating her nephrotic syndrome and maintaining the stability of her renal function over a 30-month period. Glomerular involvement of sarcoidosis needs to be considered in the differential diagnosis in cases of rapidly progressive glomerular nephritis.

Antioxidants as Potential Therapeutics for Lung Fibrosis

PubMed Central

DAY, BRIAN J.

2009-01-01

Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis is substantial, and the rationale for testing antioxidants as potential new therapeutics for lung fibrosis is appealing. Current animal models of lung fibrosis have clear involvement of ROS in their pathogenesis. New classes of antioxidant agents divided into catalytic antioxidant mimetics and antioxidant scavengers are being developed. The catalytic antioxidant class is based on endogenous antioxidant enzymes and includes the manganese-containing macrocyclics, porphyrins, salens, and the non–metal-containing nitroxides. The antioxidant scavenging class is based on endogenous antioxidant molecules and includes the vitamin E analogues, thiols, lazaroids, and polyphenolic agents. Numerous studies have shown oxidative stress to be associated with many interstitial lung diseases and that these agents are effective in attenuating fibroproliferative responses in the lung of animals and humans. PMID:17999627

Orchitis and Epididymitis in Koalas (Phascolarctos cinereus) Infected With Chlamydia pecorum.

PubMed

Johnston, S D; Deif, H H; McKinnon, A; Theilemann, P; Griffith, J E; Higgins, D P

2015-11-01

Although Chlamydia causes disease of the urethra and prostate of male koalas, its impact on the testis and epididymis has not been examined. This study describes chronic-active and granulomatous orchitis and epididymitis with interstitial fibrosis associated with infection by Chlamydia pecorum in 2 of 18 adult male koalas being euthanized at a koala hospital, 8 of which also had chlamydial prostatitis. By immunohistochemistry and transmission electron microscopy, chlamydial inclusions were demonstrated within Sertoli cells directly associated with mild inflammation surrounding intact seminiferous and epididymal tubules, marked pyogranulomatous inflammation around disrupted tubules, replacement of tubules by interstitial fibrosis, and aspermia. The presence of C. pecorum but not Chlamydia pneumoniae was detected by quantitative polymerase chain reaction of formalin-fixed tissues of the left and right testes and right epididymis in 1 animal. This is the first report of orchitis and epididymitis in a koala infected with C. pecorum. © The Author(s) 2015.

MR-guided laser-induced interstitial thermotherapy of recurrent glioblastoma multiforme: preliminary results in 16 patients.

PubMed

Schwarzmaier, Hans-Joachim; Eickmeyer, Frank; von Tempelhoff, Wernholt; Fiedler, Volkhard Ulrich; Niehoff, Hendrik; Ulrich, Slif Dagobert; Yang, Qin; Ulrich, Frank

2006-08-01

We investigated the survival after laser-induced interstitial thermotherapy in 16 patients suffering from recurrent glioblastoma multiforme. The concept underlying the intervention is the cytoreduction of the tumor tissue by local thermocoagulation. All patients received standard chemotherapy (temozolomide). The median overall survival time after the first relapse was 9.4 months, corresponding to a median overall survival time after laser irradiation of 6.9 months. During the study, however, the median survival after laser coagulation increased to 11.2 months. This survival time is substantially longer than those reported for the natural history (<5 months) or after chemotherapy (temozolomide: 5.4-7.1 months). We conclude that cytoreduction by laser irradiation might be a promising option for patients suffering from recurrent glioblastoma multiforme. In addition, the data indicate the presence of a substantial learning curve. Future work should optimize the therapeutic regimen and evaluate this treatment approach in controlled clinical trials.

Passivation of interstitial and vacancy mediated trap-states for efficient and stable triple-cation perovskite solar cells

NASA Astrophysics Data System (ADS)

Mahmud, Md Arafat; Elumalai, Naveen Kumar; Upama, Mushfika Baishakhi; Wang, Dian; Gonçales, Vinicius R.; Wright, Matthew; Xu, Cheng; Haque, Faiazul; Uddin, Ashraf

2018-04-01

The current work reports the concurrent passivation of interstitial and oxygen vacancy mediated defect states in low temperature processed ZnO electron transport layer (ETL) via Ultraviolet-Ozone (UVO) treatment for fabricating highly efficient (maximum efficiency: 16.70%), triple cation based MA0.57FA0.38Rb0.05PbI3 (MA: methyl ammonium, FA: formamidinium, Rb: rubidium) perovskite solar cell (PSC). Under UV exposure, ozone decomposes to free atomic oxygen and intercalates into the interstitial and oxygen vacancy induced defect sites in the ZnO lattice matrix, which contributes to suppressed trap-assisted recombination phenomena in perovskite device. UVO treatment also reduces the content of functional hydroxyl group on ZnO surface, that increases the inter-particle connectivity and grain size of perovskite film on UVO treated ZnO ETL. Owing to this, the perovskite film atop UVO treated ZnO film exhibits reduced micro-strain and dislocation density values, which contribute to the enhanced photovoltaic performance of PSC with modified ZnO ETL. The modified PSCs exhibit higher recombination resistance (RRec) ∼40% compared to pristine ZnO ETL based control devices. Adding to the merit, the UVO treated ZnO PSC also demonstrates superior device stability, retaining about 88% of its initial PCE in the course of a month-long, systematic degradation study.

The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.

PubMed

Kojima, Yoko; Okudela, Koji; Matsumura, Mai; Omori, Takahiro; Baba, Tomohisa; Sekine, Akimasa; Woo, Tetsukan; Umeda, Shigeaki; Takemura, Tamiko; Mitsui, Hideaki; Suzuki, Takehisa; Tateishi, Yoko; Iwasawa, Tae; Arai, Hiromasa; Tajiri, Michihiko; Ogura, Takashi; Kameda, Yoichi; Masuda, Munetaka; Ohashi, Kenich

2017-03-01

To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features. © 2016 John Wiley & Sons Ltd.

STRETCHING IMPACTS INFLAMMATION RESOLUTION IN CONNECTIVE TISSUE

PubMed Central

Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J.; Colas, Romain A.; Spite, Matthew; Serhan, Charles N.; Langevin, Helene M.

2016-01-01

Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. PMID:26588184

Left and right ventricle late remodeling following myocardial infarction in rats.

PubMed

Stefanon, Ivanita; Valero-Muñoz, María; Fernandes, Aurélia Araújo; Ribeiro, Rogério Faustino; Rodríguez, Cristina; Miana, Maria; Martínez-González, José; Spalenza, Jessica S; Lahera, Vicente; Vassallo, Paula F; Cachofeiro, Victoria

2013-01-01

The mechanisms involved in cardiac remodeling in left (LV) and right ventricles (RV) after myocardial infarction (MI) are still unclear. We assayed factors involved in collagen turnover in both ventricles following MI in rats either presenting signs of heart failure (pulmonary congestion and increased LVEDP) or not (INF-HF or INF, respectively). MI was induced in male rats by ligation of the left coronary artery. Four weeks after MI gene expression of collagen I, connective tissue growth factor (CTGF), transforming growth factor β (TGF-β) and lysyl oxidase (LOX), metalloproteinase-2 (MMP2) and tissue inhibitor metalloproteinase-2 (TIMP2) as well as cardiac hemodynamic in both ventricles were evaluated. Ventricular dilatation, hypertrophy and an increase in interstitial fibrosis and myocyte size were observed in the RV and LV from INF-HF animals, whereas only LV dilatation and fibrosis in RV was present in INF. The LV fibrosis in INF-HF was associated with higher mRNA of collagen I, CTGF, TGF-β and LOX expressions than in INF and SHAM animals, while MMP2/TIMP2 mRNA ratio did not change. RV fibrosis in INF and INF-HF groups was associated with an increase in LOX mRNA and a reduction in MMP2/TIMP2 ratio. CTGF mRNA was increased only in the INF-HF group. INF and INF-HF animals presented different patterns of remodeling in both ventricles. In the INF-HF group, fibrosis seems to be consequence of collagen production in LV, and by reductions in collagen degradation in RV of both INF and INF-HF animals.

SU-E-J-197: A Novel Optical Interstitial Fiber Spectroscopic System for Real-Time Tissue Micro-Vascular Hemodynamics Monitoring.

PubMed

Zhao, D; Campos, D; Yan, Y; Kimple, R; Jacques, S; van der Kogel, A; Kissick, M

2012-06-01

To demonstrate a novel interstitial optical fiber spectroscopic system, based on diffuse optical spectroscopies with spectral fitting, for the simultaneous monitoring of tumor blood volume and oxygen tension. The technique provides real-time, minimally-invasive and quantification of tissue micro-vascular hemodynamics. An optical fiber prototype probe characterizesthe optical transport in tissue between two large Numerical Aperture (NA) fibers of 200μm core diameter (BFH37-200, ThorLabs) spaced 3-mm apart. Two 21-Ga medical needles are used to protect fiber ends and to facilitate tissue penetration with minimum local blunt trauma in nude mice with xenografts. A 20W white light source (HL-2000-HP, Ocean Optics) is coupled to one fiber with SMA adapter. The other fiber is used to collect light, which is coupled into the spectrometer (QE65000 with Spectrasuite Operating software and OmniDriver, Ocean Optics). The wavelength response of the probe depends on the wavelength dependence of the light source, and of the light signal collection that includes considerable scatter, modeled with Monte-Carlo techniques (S. Jacques 2010 J. of Innov. Opt. Health Sci. 2 123-9). Measured spectra of tissue are normalized by a measured spectrum of a white standard, yielding the transmission spectrum. A head-and-neck xenograft on the flank of a live mouse is used for development. The optical fiber probe delivers and collects light at an arbitrary depth in the tumor. By spectral fitting of the measured transmission spectrum, an analysis of blood volume and oxygen tension is obtained from the fitting parameters in real time. A newly developed optical fiber spectroscopic system with an optical fiber probe takes spectroscopic techniques to a much deeper level in a tumor, which has potential applications for real-time monitoring hypoxic cell population dynamics for an eventual adaptive therapy metric of particular use in hypofractionated radiotherapy. © 2012 American Association of Physicists in Medicine.

High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats

PubMed Central

Shrestha, Pragyi; Sarpong, Kwaku A.; Yazdani, Saleh; el Masri, Rana; de Jong, Wilhelmina H. A.; Navis, Gerjan; Vivès, Romain R.; van den Born, Jacob

2017-01-01

Background High dietary sodium aggravates renal disease by affecting blood pressure and by its recently shown pro-inflammatory and pro-fibrotic effects. Moreover, pro-inflammatory modification of renal heparan sulfate (HS) can induce tissue remodeling. We aim to investigate if high sodium intake in normotensive rats converts renal HS into a pro-inflammatory phenotype, able to bind more sodium and orchestrate inflammation, fibrosis and lymphangiogenesis. Methods Wistar rats received a normal diet for 4 weeks, or 8% NaCl diet for 2 or 4 weeks. Blood pressure was monitored, and plasma, urine and tissue collected. Tissue sodium was measured by flame spectroscopy. Renal HS and tubulo-interstitial remodeling were studied by biochemical, immunohistochemical and qRT-PCR approaches. Results High sodium rats showed a transient increase in blood pressure (week 1; p<0.01) and increased sodium excretion (p<0.05) at 2 and 4 weeks compared to controls. Tubulo-interstitial T-cells, myofibroblasts and mRNA levels of VCAM1, TGF-β1 and collagen type III significantly increased after 4 weeks (all p<0.05). There was a trend for increased macrophage infiltration and lymphangiogenesis (both p = 0.07). Despite increased dermal sodium over time (p<0.05), renal concentrations remained stable. Renal HS of high sodium rats showed increased sulfation (p = 0.05), increased L-selectin binding to HS (p<0,05), and a reduction of sulfation-sensitive anti-HS mAbs JM403 (p<0.001) and 10E4 (p<0.01). Hyaluronan expression increased under high salt conditions (p<0.01) without significant changes in the chondroitin sulfate proteoglycan versican. Statistical analyses showed that sodium-induced tissue remodeling responses partly correlated with observed HS changes. Conclusion We show that high salt intake by healthy normotensive rats convert renal HS into high sulfated pro-inflammatory glycans involved in tissue remodeling events, but not in increased sodium storage. PMID:28594849

Transcatheter treatment of tricuspid regurgitation by caval valve implantation--experimental evaluation of decellularized tissue valves in central venous position.

PubMed

Lauten, Alexander; Laube, Adrian; Schubert, Harald; Bischoff, Sabine; Nietzsche, Sandor; Horstkötter, Kim; Poudel-Bochmann, Bhawana; Franz, Marcus; Lichtenberg, Artur; Figulla, Hans R; Akhyari, Payam

2015-01-01

Caval valve implantation has been suggested for transcatheter treatment of severe tricuspid regurgitation (TR). Combining the interventional technique with the promising surgical experience with decellularized valves, we sought to evaluate the functional and structural outcome of decellularized pericardial tissue valves (dTVs) in the low-pressure venous circulation in a chronic model of TR. Sixteen pericardial tissue valves were heterotopically implanted in the inferior and superior vena cava in a sheep model (54-98 kg; median 74.5 kg, n = 8) of severe TR. The devices were assembled using self-expanding nitinol stents and bovine pericardia decellularized by a detergent-based protocol (group dTV; n = 8). Glutaraldehyde-fixed pericardial tissue valves served as control (GaTV, n = 8). After 6 months, device function and structural maturation were analyzed using echocardiographic, histologic, immunohistologic, and electron microscopic approaches. After implantation, cardiac output increased significantly from 3.7 ± 1.1 l/min to 4.8 ± 1.1 l/min (P < 0.05) and competent valve function was verified by angiography. At 6 months, angiographic and echocardiographic evaluation revealed moderate to severe regurgitation in all GaTV. In contrast, five of the eight dTVs functioned well with only minor regurgitation. In these animals, autopsy revealed preserved valve structure with tender leaflets without signs of thrombosis or calcification. Conversely, GaTV showed severe degeneration with large calcification areas. Microscopic and histologic analysis confirmed endothelial repopulation in both valve types. However, additional interstitial reseeding was observed in decellularized valves. In the venous circulation in severe TR, decellularized valves show superior functional performance compared to Ga-fixed tissue valves. Macroscopic and microscopic analyses suggest preserved structural integrity and advanced endothelial and interstitial repopulation with evidence of less degradation in dTV. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Quantitative morphology in canine cutaneous soft tissue sarcomas.

PubMed

Simeonov, R; Ananiev, J; Gulubova, M

2015-12-01

Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas [fibrosarcoma (n = 8), liposarcoma (n = 8) and haemangiopericytoma (n = 8)], and 24 dogs with reactive connective tissue lesions [granulation tissue (n = 12) and dermal fibrosis (n = 12)] were analysed by computer-assisted nuclear morphometry. The studied morphometric parameters were: mean nuclear area (MNA; µm(2)), mean nuclear perimeter (MNP; µm), mean nuclear diameter (MND mean; µm), minimum nuclear diameter (Dmin; µm) and maximum nuclear diameter (Dmax; µm). The study aimed to evaluate (1) possibility for quantitative differentiation of soft tissue sarcomas from reactive connective tissue lesions and (2) by using cytomorphometry, to differentiate the various histopathological soft tissue sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric parameters (except for Dmax) were statistically significantly higher in reactive connective tissue processes than in soft tissue sarcomas. At the same time, however, there were no considerable differences among the different sarcoma subtypes. The results demonstrated that the quantitative differentiation of reactive connective tissue processes from soft tissue sarcomas in dogs is possible, but the same was not true for the different canine soft tissue sarcoma subtypes. Further investigations on this topic are necessary for thorough explication of the role of quantitative morphology in the diagnostics of mesenchymal neoplasms and tumour-like fibrous lesions in dogs. © 2014 John Wiley & Sons Ltd.

FRET excited ratiometric oxygen sensing in living tissue

PubMed Central

Ingram, Justin M.; Zhang, Chunfeng; Xu, Jian; Schiff, Steven J.

2013-01-01

Dynamic analysis of oxygen (O2) has been limited by the lack of a real-time, quantitative, and biocompatible sensor. To address these demands, we designed a ratiometric optode matrix consisting of the phosphorescence quenching dye platinum (II) octaethylporphine ketone (PtOEPK) and nanocystal quantum dots (NQDs), which when embedded within an inert polymer matrix allows long-term pre-designed excitation through fluorescence resonance energy transfer (FRET). Depositing this matrix on various glass substrates allowed the development of a series of optical sensors able to measure interstitial oxygen concentration [O2] with several hundred millisecond temporal resolution in varying biological microdomains of active brain tissue. PMID:23333398

Fuller's earth (montmorillonite) pneumoconiosis.

PubMed Central

Gibbs, A R; Pooley, F D

1994-01-01

A fuller's earth worker developed signs of pneumoconiosis. Pathological examination of the lung tissues showed interstitial collections of dust laden macrophages associated with mild fibrosis. Mineralogical analysis showed a high content of montmorillonite. This study shows that a pneumoconiosis can result from prolonged heavy exposure to calcium montmorillonite (fuller's earth) in the absence of quartz. The disease is relatively mild and associated with little clinical disability. Images Figure 1 Figure 2 PMID:7951799