Unidirectional fiber-reinforced composite as an oral implant abutment material: Experimental studies of E-glass fiber/BisGMA-TEGDMA polymer in vitro

Fiber-reinforced composites (FRCs) are a new group of non-metallic biomaterials showing a growing popularity in many dental and medical applications. As an oral implant material, FRC is biocompatible in bone tissue environment. Soft tissue integration to FRC polymer material is unclear. This series of in vitro studies aimed at evaluating unidirectional E-glass FRC polymer in terms of mechanical, chemical, and biological properties in an attempt to develop a new non-metallic oral implant abutment alternative. Two different types of substrates were investigated: (a) Plain polymer (BisGMA 50%–TEGDMA 50%) and (b) Unidirectional FRC. The mechanical behavior of high fiber-density FRCs was assessed using a three-point bending test. Surface characterization was performed using scanning electron and spinning disk confocal microscopes. The surface wettability/energy was determined using sessile drop method. The blood response, including blood-clotting ability and platelet morphology was evaluated. Human gingival fibroblast cell responses - adhesion kinetics, adhesion strength, and proliferation activity - were studied in cell culture environment using routine test conditions. A novel tissue culture method was developed and used to evaluate porcine gingival tissue graft attachment and growth on the experimental composite implants. The analysis of the mechanical properties showed that there is a direct proportionality in the relationship between E-glass fiber volume fraction and toughness, modulus of elasticity, and load bearing capacity; however, flexural strength did not show significant improvement when high fiber-density FRC is used. FRCs showed moderate hydrophilic properties owing to the presence of exposed glass fibers on the polymer surface. Blood-clotting time was shorter on FRC substrates than on plain polymer. The FRC substrates also showed higher platelet activation state than plain polymer substrates. Fibroblast cell adhesion strength and proliferation rate were highly pronounced on FRCs. A tissue culture study revealed that gingival epithelium and connective tissue established an immediate close contact with both plain polymer and FRC implants. However, FRC seemed to guide epithelial migration outwards from the tissue/implant interface. Due to the anisotropic and hydrophilic nature of FRC, it can be concluded that this material enhances biological events related with soft tissue integration on oral implant surface.

Home Blood Pressure Measurement – Epidemiology and Clinical Application

Verenpaineen kotimittaus − epidemiologia ja kliininen käyttö Kohonnutta verenpainetta, maailmanlaajuisesti merkittävintä ennenaikaiselle kuolemalle altistavaa riskitekijää, ei voida tunnistaa tai hoitaa ilman tarkkoja ja käytännöllisiä verenpaineen mittausmenetelmiä. Verenpaineen kotimittaus on saavuttanut suuren suosion potilaiden keskuudessa. Lääkärit eivät ole kuitenkaan vielä täysin hyväksyneet verenpaineen kotimittausta, sillä riittävä todistusaineisto sen toimivuudesta ja eduista on puuttunut. Tämän tutkimuksen tarkoituksena oli osoittaa, että kotona mitattu verenpaine (kotipaine) on perinteistä vastaanotolla mitattua verenpainetta (vastaanottopaine) tarkempi, ja että se on tehokas myös kliinisessä käytössä. Tutkimme kotipaineen käyttöä verenpainetaudin diagnosoinnissa ja hoidossa. Lisäksi tarkastelimme kotipaineen yhteyttä verenpainetaudin aiheuttamiin kohde-elinvaurioihin. Ensimmäinen aineisto, joka oli edustava otos Suomen aikuisväestöstä, koostui 2 120 45–74-vuotiaasta tutkimushenkilöstä. Tutkittavat mittasivat kotipainettaan viikon ajan ja osallistuivat terveystarkastukseen, johon sisältyi kliinisen tutkimuksen ja haastattelun lisäksi sydänfilmin otto ja vastaanottopaineen mittaus. 758 tutkittavalle suoritettiin lisäksi kaulavaltimon seinämän intima-mediakerroksen paksuuden (valtimonkovettumataudin mittari) mittaus ja 237:lle valtimon pulssiaallon nopeuden (valtimojäykkyyden mittari) mittaus. Toisessa aineistossa, joka koostui 98 verenpainetautia sairastavasta potilaasta, hoitoa ohjattiin satunnaistamisesta riippuen joko ambulatorisen eli vuorokausirekisteröinnillä mitatun verenpaineen tai kotipaineen perusteella. Vastaanottopaine oli kotipainetta merkittävästi korkeampi (systolisen/diastolisen paineen keskiarvoero oli 8/3 mmHg) ja yksimielisyys verenpainetaudin diagnoosissa kahden menetelmän välillä oli korkeintaan kohtalainen (75 %). 593 tutkittavasta, joilla oli kohonnut verenpaine vastaanotolla, 38 %:lla oli normaali verenpaine kotona eli ns. valkotakkiverenpaine. Verenpainetauti voidaan siis ylidiagnosoida joka kolmannella potilaalla seulontatilanteessa. Valkotakkiverenpaine oli yhteydessä lievästi kohonneeseen verenpaineeseen, matalaan painoindeksiin ja tupakoimattomuuteen, muttei psykiatriseen sairastavuuteen. Valkotakkiverenpaine ei kuitenkaan vaikuttaisi olevan täysin vaaraton ilmiö ja voi ennustaa tulevaa verenpainetautia, sillä siitä kärsivien sydän- ja verisuonitautien riskitekijäprofiili oli normaalipaineisten ja todellisten verenpainetautisten riskitekijäprofiilien välissä. Kotipaineella oli vastaanottopainetta vahvempi yhteys verenpainetaudin aiheuttamiin kohde-elinvaurioihin (intima-mediakerroksen paksuus, pulssiaallon nopeus ja sydänfilmistä todettu vasemman kammion suureneminen). Kotipaine oli tehokas verenpainetaudin hoidon ohjaaja, sillä kotipaineeseen ja ambulatoriseen paineeseen, jota on pidetty verenpainemittauksen ”kultaisena standardina”, perustuva lääkehoidon ohjaus johti yhtä hyvään verenpaineen hallintaan. Tämän ja aikaisempien tutkimusten tulosten pohjalta voidaan todeta, että verenpaineen kotimittaus on selkeä parannus perinteiseen vastaanotolla tapahtuvaan verenpainemittaukseen verrattuna. Verenpaineen kotimittaus on käytännöllinen, tarkka ja laajasti saatavilla oleva menetelmä, josta voi tulla jopa ensisijainen vaihtoehto verenpainetautia diagnosoitaessa ja hoitaessa. Verenpaineen mittauskäytäntöön tarvitaan muutos, sillä näyttöön perustuvan lääketieteen perusteella vaikuttaa, että vastaanotolla tapahtuvaa verenpainemittausta tulisi käyttää vain seulontatarkoitukseen.

The Regulation of Skeletal and Cardiac Muscle Blood Flow in Humans. Studies by positron emission tomography with special reference to exercise, adenosine and nitric oxide

Virtually every cell and organ in the human body is dependent on a proper oxygen supply. This is taken care of by the cardiovascular system that supplies tissues with oxygen precisely according to their metabolic needs. Physical exercise is one of the most demanding challenges the human circulatory system can face. During exercise skeletal muscle blood flow can easily increase some 20-fold and its proper distribution to and within muscles is of importance for optimal oxygen delivery. The local regulation of skeletal muscle blood flow during exercise remains little understood, but adenosine and nitric oxide may take part in this process. In addition to acute exercise, long-term vigorous physical conditioning also induces changes in the cardiovasculature, which leads to improved maximal physical performance. The changes are largely central, such as structural and functional changes in the heart. The function and reserve of the heart’s own vasculature can be studied by adenosine infusion, which according to animal studies evokes vasodilation via it’s a_2A receptors. This has, however, never been addressed in humans in vivo and also studies in endurance athletes have shown inconsistent results regarding the effects of sport training on myocardial blood flow. This study was performed on healthy young adults and endurance athletes and local skeletal and cardiac muscle blod flow was measured by positron emission tomography. In the heart, myocardial blood flow reserve and adenosine A_2A receptor density, and in skeletal muscle, oxygen extraction and consumption was also measured. The role of adenosine in the control of skeletal muscle blood flow during exercise, and its vasodilator effects, were addressed by infusing competitive inhibitors and adenosine into the femoral artery. The formation of skeletal muscle nitric oxide was also inhibited by a drug, with and without prostanoid blockade. As a result and conclusion, it can be said that skeletal muscle blood flow heterogeneity decreases with increasing exercise intensity most likely due to increased vascular unit recruitment, but exercise hyperemia is a very complex phenomenon that cannot be mimicked by pharmacological infusions, and no single regulator factor (e.g. adenosine or nitric oxide) accounts for a significant part of exercise-induced muscle hyperemia. However, in the present study it was observed for the first time in humans that nitric oxide is not only important regulator of the basal level of muscle blood flow, but also oxygen consumption, and together with prostanoids affects muscle blood flow and oxygen consumption during exercise. Finally, even vigorous endurance training does not seem to lead to supranormal myocardial blood flow reserve, and also other receptors than A_2A mediate the vasodilator effects of adenosine. In respect to cardiac work, atheletes heart seems to be luxuriously perfused at rest, which may result from reduced oxygen extraction or impaired efficiency due to pronouncedly enhanced myocardial mass developed to excel in strenuous exercise.

The regulation and function of collagenase-3 (MMP-13) in cutaneous wound healing and squamous cell carcinoma

Matrix metalloproteinase-13 (MMP-13) is a potent proteolytic enzyme, whose expression has been previously associated with fetal bone development and postnatal bone remodeling and with adult gingival wound healing. MMP-13 is also known to be involved in the growth and invasion of various cancers including squamous cell carcinoma (SCC) of the skin. The aim of this study was to further elucidate the function and regulation of MMP-13 in wound repair and cancer. In this study, it was shown that fetal skin fibroblasts express MMP-13 in response to transforming growth factor-β in a p38 MAP kinase dependent manner. In addition, MMP-13 was found to be expressed in vivo by wound fibroblasts in human fetal skin grafted on SCID mice. Adenovirally delivered expression of MMP-13 enhanced collagen matrix contraction by fibroblasts in vitro in association with altered cytoskeletal structure, enhanced proliferation and survival. These results indicate that MMP-13 is involved in cell-mediated collagen matrix remodeling and suggest a role for MMP-13 in superior matrix remodeling and scarless healing of fetal skin wounds. Using an MMP-13 deficient mouse strain, it was shown that MMP-13 is essential for the normal development of experimental granulation tissue in mice. MMP-13 was implicated in the regulation of myofibroblast function and angiogenesis and the expression of genes involved in cellular proliferation and movement, immune response, angiogenesis and proteolysis. Finally, epidermal mitogen, keratinocyte growth factor (KGF) was shown to suppress the malignant properties of skin SCC cells by downregulating the expression of several target genes with potential cancer promoting properties, including MMP-13, and by reducing SCC cell invasion. These results provide evidence that MMP-13 potently regulates cell viability, myofibroblast function and angiogenesis associated with wound healing and cancer. In addition, fibroblasts expressing MMP-13 show high collagen reorganization capacity. Moreover, the results suggest that KGF mediates the anti-cancer effects on skin SCC

Interoperability specifications and an automatic validation tool as a key factor for the support of a repository ecosystem

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Modulation of TGF-β signaling by Hypoxia

A tumor is a fast-growing malignant tissue. This creates areas inside the tumor that are distant from local blood vessels to be able to get enough oxygen. This hypoxic condition activates a transcription factor called hypoxia inducible factor (HIF). HIF responses help a cell to adapt to decreased oxygen by activating glycolytic and angiogenesis pathways and by regulating apoptotic responses. Hypoxia drives the upregulation of a growth factor called transforming growth factor beta (TGF-beta). Similar to a hypoxia response, TGF is an important regulator of cell fate. TGF-β and HIF pathways regulate partially overlapping target genes. This regulation can also be cooperative. The TGF-beta signal is initiated by activation of plasma membrane receptors that then activate effector proteins called small mothers against decapentaplegic (Smad) homologs. In healthy tissue, TGF-β keeps cell proliferation and growth under control. During cancer progression, TGF-beta has shown a dual role, whereby it inhibits initial tumor formation but, conversely, in an existent tumor, TGF-beta drives malignant progression. Along with HIF and TGF-beta also protein dephosphorylation is an important regulatory mechanism of cell fate. Protein dephosphorylation is catalyzed by protein phosphatases such as Protein phosphatase 2A (PP2A). PP2A is a ubiquitous phosphatase that can exist in various active forms. PP2A can specifically regulate TGF-beta signaling either by enhancing or inhibiting the receptor activity. This work demonstrates that during hypoxia, PP2A is able to fine-tune TGF-beta signal by specifically targeting Smad3 effector in a Smad7-dependent manner. Inactivation of Smad3 in hypoxia leads to malignant conversion of TGF-beta signaling.

Cardiac Imaging in the Diagnosis of Coronary Artery Disease: The Value of Quantitative Imaging of Myocardial Perfusion and Deformation

Atherosclerosis is a chronic and progressive disease of the vasculature. Increasing coronary atherosclerosis can lead to obstructive coronary artery disease (CAD) or myocardial infarction. Computed tomography angiography (CTA) allows noninvasive assessment of coronary anatomy and quantitation of atherosclerotic burden. Myocardial blood flow (MBF) can be accurately measured in absolute terms (mL/g/min) by positron emission tomography (PET) with [15O] H O as a radiotracer. We studied the coronary microvascular dysfunction as a risk factor for future coronary calcification in healthy young men by measuring the coronary flow reserve (CFR) which is the ratio between resting and hyperemic MBF. Impaired vasodilator function was not linked with accelerated atherosclerosis 11 years later. Currently, there is a global interest in quantitative PET perfusion imaging. We established optimal thresholds of [15O] H O PET perfusion for diagnosis of CAD (hyperemic MBF of 2.3 mL/g/min and CFR of 2.5) in the first multicenter study of this type (Turku, Amsterdam and Uppsala). In myocardial bridging a segment of the coronary artery travels inside the myocardium and can be seen as intramural course (CTA) or systolic compression (invasive coronary angiography). Myocardial bridging is frequently linked with proximal atherosclerotic plaques. We used quantitative [15O] H O PET perfusion to evaluate the hemodynamic effects of myocardial bridging. Myocardial bridging was not associated with decreased absolute MBF or increased atherosclerotic burden. Speckle tracking allows quantitative echocardiographic imaging of myocardial deformation. Speckle tracking during dobutamine stress echocardiography was feasible and comparable to subjective wall motion analysis in the diagnosis of CAD. In addition, it correctly risk stratified patients with multivessel disease and extensive ischemia.