Myoblast transplantation and adenoviral VEGF-C transfer in porcine model of coronary artery disease

Heart failure is a common and highly challenging medical disorder. The progressive increase of elderly population is expected to further reflect in heart failure incidence. Recent progress in cell transplantation therapy has provided a conceptual alternative for treatment of heart failure. Despite improved medical treatment and operative possibilities, end-stage coronary artery disease present a great medical challenge. It has been estimated that therapeutic angiogenesis would be the next major advance in the treatment of ischaemic heart disease. Gene transfer to augment neovascularization could be beneficial for such patients. We employed a porcine model to evaluate the angiogenic effect of vascular endothelial growth factor (VEGF)-C gene transfer. Ameroid-generated myocardial ischemia was produced and adenovirus encoding (ad)VEGF-C or β-galactosidase (LacZ) gene therapy was given intramyocardially during progressive coronary stenosis. Angiography, positron emission tomography (PET), single photon emission computed tomography (SPECT) and histology evidenced beneficial affects of the adVEGF-C gene transfer compared to adLacZ. The myocardial deterioration during progressive coronary stenosis seen in the control group was restrained in the treatment group. We observed an uneven occlusion rate of the coronary vessels with Ameroid constrictor. We developed a simple methodological improvement of Ameroid model by ligating of the Ameroid–stenosed coronary vessel. Improvement of the model was seen by a more reliable occlusion rate of the vessel concerned and a formation of a rather constant myocardial infarction. We assessed the spontaneous healing of the left ventricle (LV) in this new model by SPECT, PET, MRI, and angiography. Significant spontaneous improvement of myocardial perfusion and function was seen as well as diminishment of scar volume. Histologically more microvessels were seen in the border area of the lesion. Double staining of the myocytes in mitosis indicated more cardiomyocyte regeneration at the remote area of the lesion. The potential of autologous myoblast transplantation after ischaemia and infarction of porcine heart was evaluated. After ligation of stenosed coronary artery, autologous myoblast transplantation or control medium was directly injected into the myocardium at the lesion area. Assessed by MRI, improvement of diastolic function was seen in the myoblast-transplanted animals, but not in the control animals. Systolic function remained unchanged in both groups.Pitkälle edennyt sydämen vajaatoiminta on hyvin vaikeahoitoinen tauti. Vanhuusväestön suhteellinen lisääntyminen lisää taudin merkittävyyttä ja sydänlihaksen solusiirtoja on ehdotettu uudeksi vaihtoehtoiseksi hoitomuodoksi. Huolimatta parantuneesta lääkehoidosta ja kehittyneistä pallolaajennus- ja leikkausmenetelmistä, loppuvaiheen sepelvaltimotauti on lääketieteellinen haaste. On arvioitu, että geenihoito olisi seuraava merkittävä hoitomenetelmä vaikeassa sepelvaltimotaudissa. Kokeilimme koe-eläimellä adenoviruksella siirretyn VEGF-C-kasvutekijän vaikutusta uudissuonten kehittymiseen. Sialle asetettiin hitaasti elimistössä turpoava rengastin sepelvaltimon tyveen. Kolme viikkoa rengastimen asettamisesta sioille siirrettiin VEGF-C-hoitogeeni tai kontrolligeeni hapenpuutetta kärsivälle sydänlihaksen alueelle. Sydänlihaksen verenkierto tutkittiin verisuonten varjoainekuvauksilla, sekä PET- ja SPECT kuvauksin. Lopuksi tutkittiin kudosnäytteet. Hoitoryhmällä havaittiin merkittävästi enemmän uudissuonia ja rengastimen aiheuttama sydänlihaksen toiminnanvajaus ei edennyt, toisin kuin kontrolligeeniä saaneilla eläimillä. Kyseinen rengastin on käytetyin laite sepelvaltimotaudin mallintamisessa isoeläimellä. Havaitsimme kuitenkin ahtautuma-asteen vaihtelevan yksilöiden välillä. Kehitimme yksinkertaisen menetelmän, jossa kiristimen asetuksen yhteydessä jätettiin suonen ympärille sulkulanka. Langalla varmistetaan suonen tukkeutuminen kolmen viikon kohdalla, kun luontainen uudissuonimuodostus on kehittynyt sydämen suojaksi. Menetelmä osoittautui toimivaksi ja kuvasimme uuden mallin luontaisen paranemistaipumuksen magneetti- SPECT ja PET- kuvauksin sekä verisuonten varjoainekuvauksilla. Kudostutkimuksissa havaitsimme immunohistokemiallisin kaksoisvärjäyksin sydänlihassolujen tumien jakautumista luontaisen paranemisen merkkinä. Aiemmin on uskottu, että sydänlihassolujen jakaantumista ei tapahdu enää hyvin varhaisen lapsuuden jälkeen. Myoblastit ovat luurankolihassolujen esiasteita, joista voi kehittyä uusia lihassoluja. Kokeilimme eläimestä itsestään kerättyjen myoblastien vaikutusta sydänlihaskuolion ja -hapenpuutteen hoidossa. Sioille luotiin pienet sydäninfarktit ja hapenpuutteesta kärsivä alue. Jokaisesta eläimestä kerättiin lihasnäytteet, joista myoblastit eristettiin ja solujen lukumäärää lisättiin miljooniin laboratoriossa kasvattamalla. Siat saivat sokkoutetusti joko myoblasti-solusiirron tai kontrolliliuosta sydämen vaurioalueelle. Sydänlihaksen toiminta ja -hapensaanti arvioitiin magneetti- ja sepelvaltimoiden varjoainekuvauksin. Myoblasteja saaneilla eläimillä sydämen diastolinen toiminta oli parempi kuin kontrolliryhmällä. Tämä tutkimussarja tukee sydämen solu- ja geenihoitojen vaikuttavuutta sydäntautien hoidossa

Repeated Daily Use of Dual-Light Antibacterial Photodynamic Therapy in Periodontal Disease—A Case Report

Good oral hygiene at home is the foundation for optimal treatment response and long-term periodontal disease control. Antibacterial photodynamic therapy (aPDT) provides a very potent adjunctive treatment for plaque control. However, the literature regarding repeated aPDT use is sparse. aPDT has been a modality applied mainly in the dental office environment, and when applied once a year or every few months, the results have been usually disappointing. Recently, LED development has brought aPDT for repeated and practical use at home. We present the very positive results and clinical outcome of daily applied dual-light aPDT-technology treatment in conjunction with mechanical cleaning of a 78-year-old male patient with severe periodontal disease (Stage IV and Grade B)

Chronic Disease Burden After Congenital Heart Surgery : A 47-Year Population-Based Study With 99% Follow-Up

Background Postoperative morbidity is an increasingly important outcome measure of patients who have undergone congenital heart surgery (CHS). We examined late postoperative morbidity after CHS on the basis of patients' government-issued medical special reimbursement rights. Methods and Results Between 1953 and 2009, 10 635 patients underwent CHS at Conclusions Chronic cardiac and noncardiac sequelae are common after CHS regardless of the severity of the defect, underscoring the importance of long-term follow-up of all patients after CHS.Peer reviewe

Repeated Home-Applied Dual-Light Antibacterial Photodynamic Therapy Can Reduce Plaque Burden, Inflammation, and aMMP-8 in Peri-Implant Disease—A Pilot Study

Until now, in clinical dentistry, antibacterial photodynamic therapy (aPDT) has been restricted to in-office treatments, which hampers repeated applications. This pilot study tested the benefit of a commercially available Lumoral® device designed for regular periodontal dual-light aPDT treatment at home. Seven patients with peri-implant disease applied dual-light aPDT daily in addition to their normal dental hygiene for four weeks. A single Lumoral® treatment includes an indocyanine green mouth rinse followed by 40 J/cm2 radiant exposure to a combination of 810 nm and 405 nm light. A point-of-care analysis of active-matrix metalloproteinase (aMMP-8), visible plaque index (VPI), bleeding on probing (BOP), and peri-implant pocket depth (PPD) measurements was performed on day 0, day 15, and day 30. Reductions in aMMP-8 (p = 0.047), VPI (p = 0.03), and BOP (p = 0.03) were observed, and PPD was measured as being 1 mm lower in the implant (p = ns). These results suggest a benefit of regular application of dual-light aPDT in peri-implantitis. Frequently repeated application can be a promising approach to diminishing the microbial burden and to lowering the tissue destructive proteolytic and inflammatory load around dental implants. Further studies in larger populations are warranted to show the long-term benefits

Epicardial delivery of autologous atrial appendage micrografts during coronary artery bypass surgery - safety and feasibility study

BioMed Central open acces

Repeated Home-Applied Dual-Light Antibacterial Photodynamic Therapy Can Reduce Plaque Burden, Inflammation, and aMMP-8 in Peri-Implant Disease-A Pilot Study

Until now, in clinical dentistry, antibacterial photodynamic therapy (aPDT) has been restricted to in-office treatments, which hampers repeated applications. This pilot study tested the benefit of a commercially available Lumoral(R) device designed for regular periodontal dual-light aPDT treatment at home. Seven patients with peri-implant disease applied dual-light aPDT daily in addition to their normal dental hygiene for four weeks. A single Lumoral(R) treatment includes an indocyanine green mouth rinse followed by 40 J/cm(2) radiant exposure to a combination of 810 nm and 405 nm light. A point-of-care analysis of active-matrix metalloproteinase (aMMP-8), visible plaque index (VPI), bleeding on probing (BOP), and peri-implant pocket depth (PPD) measurements was performed on day 0, day 15, and day 30. Reductions in aMMP-8 (p = 0.047), VPI (p = 0.03), and BOP (p = 0.03) were observed, and PPD was measured as being 1 mm lower in the implant (p = ns). These results suggest a benefit of regular application of dual-light aPDT in peri-implantitis. Frequently repeated application can be a promising approach to diminishing the microbial burden and to lowering the tissue destructive proteolytic and inflammatory load around dental implants. Further studies in larger populations are warranted to show the long-term benefits.Peer reviewe

Repeated Home-Applied Dual-Light Antibacterial Photodynamic Therapy Can Reduce Plaque Burden, Inflammation, and aMMP-8 in Peri-Implant Disease—A Pilot Study

Until now, in clinical dentistry, antibacterial photodynamic therapy (aPDT) has been restricted to in-office treatments, which hampers repeated applications. This pilot study tested the benefit of a commercially available Lumoral® device designed for regular periodontal dual-light aPDT treatment at home. Seven patients with peri-implant disease applied dual-light aPDT daily in addition to their normal dental hygiene for four weeks. A single Lumoral® treatment includes an indocyanine green mouth rinse followed by 40 J/cm2 radiant exposure to a combination of 810 nm and 405 nm light. A point-of-care analysis of active-matrix metalloproteinase (aMMP-8), visible plaque index (VPI), bleeding on probing (BOP), and peri-implant pocket depth (PPD) measurements was performed on day 0, day 15, and day 30. Reductions in aMMP-8 (p = 0.047), VPI (p = 0.03), and BOP (p = 0.03) were observed, and PPD was measured as being 1 mm lower in the implant (p = ns). These results suggest a benefit of regular application of dual-light aPDT in peri-implantitis. Frequently repeated application can be a promising approach to diminishing the microbial burden and to lowering the tissue destructive proteolytic and inflammatory load around dental implants. Further studies in larger populations are warranted to show the long-term benefits

Kantasoluista sykkiviä sydänsoluja

Täsmädiagnostiikkaa, yksilöllistä hoidon optimointia ja räätälöityjä soluhoitoja Sydäninfarkti aiheuttaa sydämen arpeutumisen ja toimintakyvyn menetyksen, koska sydän ei pysty itse korjaamaan vahingoittunutta aluetta. Lisääntynyt kantasolutietämys on herättänyt toiveita uusien hoitomuotojen kehittämisestä sydänlihastuhon korjaukseen. Sitä onkin tutkittu viemällä sydämeen erilaisia aikuisessa ihmisessä olevia kantasoluja, mutta valitettavasti tutkimuksissa tehtyjen hoitojen teho on ollut toistaiseksi vähäinen. Yksi erittäin merkittävä uusi tutkimuksen kohde ovat niin sanotut erittäin monikykyiset kantasolut (alkion kantasolut ja aikuisen uudelleenohjelmoidut kantasolut eli iPS-solut). Nämä molemmat ovat kantasoluja, jotka pystyvät periaatteessa erilaistumaan kaikiksi yksilön soluiksi. iPS-soluja tuotetaan aikuisen jo erilaistuneista soluista, ja ne sisältävät saman genomin kaikkine virheineen kuin solunäytteen luovuttajalla on. iPS-solujen erilaistaminen sydänsoluiksi onkin mahdollistanut esimerkiksi erilaisten perinnöllisten tautien patofysiologian tutkimista laboratorio-olosuhteissa. Kantasoluista erilaistettuja sydänlihassoluja tutkitaan myös lääketestauksessa ja niiden uskotaan mullistavan sekä lääkekehityksen että uusien lääkkeiden turvallisuustestaukset