| Anti-Fas Gene Therapy Prevents Doxorubicin-Induced Acute Cardiotoxicity through Mechanisms Independent of Apoptosis.
December 26, 2009 at 8:22 am
|
| | Anti-Fas Gene Therapy Prevents Doxorubicin-Induced Acute Cardiotoxicity through Mechanisms Independent of Apoptosis. Am J Pathol. 2009 Dec 24; Authors: Miyata S, Takemura G, Kosai KI, Takahashi T, Esaki M, Li L, Kanamori H, Maruyama R, Goto K, Tsujimoto A, Takeyama T, Kawaguchi T, Ohno T, Nishigaki K, Fujiwara T, Fujiwara H, Minatoguchi S Activation of Fas signaling is a key mediator of doxorubicin cardiotoxicity, which involves both cardiomyocyte apoptosis and myocardial inflammation. In this study, acute cardiotoxicity was induced in mice by doxorubicin, and some mice simultaneously received an intramuscular injection of adenoviral vector encoding mouse soluble Fas (sFas) gene (Ad.CAG-sFas), an inhibitor of Fas/Fas ligand interaction. Two weeks later, left ventricular dilatation and dysfunction were apparent in the LacZ-treated control group, but both were significantly mitigated in the sFas-treated group. The in situ nick-end labeling-positive rate were similar in the two groups, and although electron microscopy revealed cardiomyocyte degeneration, no apoptotic structural features and no activation of caspases were detected, suggesting an insignificant role of apoptosis in this model. Instead, sFas treatment reversed doxorubicin-induced down-regulation of GATA-4 and attenuated ubiquitination of myosin heavy chain and troponin I to preserve these sarcomeric proteins. In addition, doxorubicin-induced significant leukocyte infiltration, fibrosis, and oxidative damage to the myocardium, all of which were largely reversed by sFas treatment. sFas treatment also suppressed doxorubicin-induced p53 overexpression, phosphorylation of c-Jun N-terminal kinase, c-Jun, and inhibitor of nuclear factor-kappaB, as well as production of cyclooxygenase-2 and monocyte chemoattractant protein-1, and it restored extracellular signal-regulated kinase activation. Therefore, sFas gene therapy prevents the progression of doxorubicin-induced acute cardiotoxicity, with accompanying attenuation of the cardiomyocyte degeneration, inflammation, fibrosis, and oxidative damage caused by Fas signaling. PMID: 20035047 [PubMed - as supplied by publisher] |
| Dental implants placed into alveolar clefts reconstructed with tongue flaps and bone grafts.
December 26, 2009 at 8:22 am
|
| | Dental implants placed into alveolar clefts reconstructed with tongue flaps and bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Dec 22; Authors: Sándor GK, Carmichael RP, Brkovic BM OBJECTIVE: The aim of this study was to describe a case series using surgical and prosthodontic modifications of tongue flaps necessary to adapt them for use in the reconstruction of large cleft deformities refractory to customary measures using dental implants and to study their outcomes in patients with complex cleft lip and palate deformities. STUDY DESIGN: Five patients were treated with iliac crest bone grafts and covered by anteriorly based tongue flaps divided at either 3 or 4 weeks after surgery. The patients were followed clinically and radiographically for 3-12 years after placement of their dental implants to monitor implant survival and success. RESULTS: One of the 5 patients suffered a partial tongue flap detachment, graft dehiscence, and recurrence of an oronasal fistula, which was successfully treated by shifting the tongue flap tissue from its new location in the palate. A total of 18 dental implants were placed into bone-grafted tissue covered by the tongue flaps. There was 1 implant failure. There were no cases of periimplantitis or bone loss in the 17 surviving implants. CONCLUSIONS: Tongue flaps are rarely used clinical entities with a very narrow range of indications. Tongue flaps are useful in the preprosthetic reconstruction of select cases with large residual oronasal fistulae with soft tissue deficits due to scarring from previously failed surgery. Tongue flaps are extremely stressful procedures for patients to endure. Patient selection is of the utmost importance. PMID: 20034822 [PubMed - as supplied by publisher] |
| The contribution of human synovial stem cells to skeletal muscle regeneration.
December 26, 2009 at 8:22 am
|
| | The contribution of human synovial stem cells to skeletal muscle regeneration. Neuromuscul Disord. 2009 Dec 22; Authors: Meng J, Adkin CF, Arechavala-Gomeza V, Boldrin L, Muntoni F, Morgan JE Stem cell therapy holds promise for treating muscle diseases. Although satellite cells regenerate skeletal muscle, they only have a local effect after intra-muscular transplantation. Alternative cell types, more easily obtainable and systemically-deliverable, were therefore sought. Human synovial stem cells (hSSCs) have been reported to regenerate muscle fibres and reconstitute the satellite cell pool. We therefore determined if these cells are able to regenerate skeletal muscle after intra-muscular injection into cryodamaged muscles of Rag2-/gamma chain-/C5-mice. We found that hSSCs possess only limited capacity to undergo myogenic differentiation in vitro or to contribute to muscle regeneration in vivo. However, this is enhanced by over-expression of human MyoD1. Interestingly, hSSCs express extracellular matrix components laminin alpha2 and collagen VI within grafted muscles. Therefore, despite their limited capacity to regenerate skeletal muscle, hSSCs could play a role in treating muscular dystrophies secondary to defects in extracellular matrix proteins. PMID: 20034794 [PubMed - as supplied by publisher] |
| In vitro generation of mechanically functional cartilage grafts based on adult human stem cells and 3D-woven poly(varepsilon-caprolactone) scaffolds.
December 26, 2009 at 8:22 am
|
| | In vitro generation of mechanically functional cartilage grafts based on adult human stem cells and 3D-woven poly(varepsilon-caprolactone) scaffolds. Biomaterials. 2009 Dec 22; Authors: Valonen PK, Moutos FT, Kusanagi A, Moretti MG, Diekman BO, Welter JF, Caplan AI, Guilak F, Freed LE Three-dimensionally woven poly(varepsilon-caprolactone) (PCL) scaffolds were combined with adult human mesenchymal stem cells (hMSC) to engineer mechanically functional cartilage constructs in vitro. The specific objectives were to: (i) produce PCL scaffolds with cartilage-like mechanical properties, (ii) demonstrate that hMSCs formed cartilage after 21 days of culture on PCL scaffolds, and (iii) study effects of scaffold structure (loosely vs. tightly woven), culture vessel (static dish vs. oscillating bioreactor), and medium composition (chondrogenic additives with or without serum). Aggregate moduli of 21-day constructs approached normal articular cartilage for tightly woven PCL cultured in bioreactors, were lower for tightly woven PCL cultured statically, and lowest for loosely woven PCL cultured statically (p < 0.05). Construct DNA, total collagen, and glycosaminoglycans (GAG) increased in a manner dependent on time, culture vessel, and medium composition. Chondrogenesis was verified histologically by rounded cells within a hyaline-like matrix that immunostained for collagen type II but not type I. Bioreactors yielded constructs with higher collagen content (p < 0.05) and more homogenous matrix than static controls. Chondrogenic additives yielded constructs with higher GAG (p < 0.05) and earlier expression of collagen II mRNA if serum was not present in medium. These results show feasibility of functional cartilage tissue engineering from hMSC and 3D-woven PCL scaffolds. PMID: 20034665 [PubMed - as supplied by publisher] |
| Anatomical changes in the primary visual cortex (V1) of the congenitally blind Crx-/-mouse.
December 26, 2009 at 8:22 am
|
| | Anatomical changes in the primary visual cortex (V1) of the congenitally blind Crx-/-mouse. Neuroscience. 2009 Dec 21; Authors: Goldshmit Y, Galley S, Foo D, Sernagor E, Bourne JA Mutations in the human cone-rod homeobox ( Crx) gene are associated with retinal dystrophies such as Leber Congenital Amaurosis (LCA), characterized by complete or near complete absence of vision from birth. The photoreceptors of Crx-/- mice lack outer segments, and therefore cannot capture light signals through rods and cones, thus resulting in a lack of normal retinal ganglion cell activity from birth. Using specific antibodies to subsets of neurons and markers of activity, we examined the impact of this absence of sensory input on the development of the primary visual cortex (V1) in early postnatal Crx-/-mice, before wiring of the visual system is complete, and in adulthood. We revealed that Crx-/-mice did not exhibit gross anatomical differences in V1; however, they exhibited significantly fewer calcium-binding protein (parvalbumin and calbindin-D28k) expressing interneurons, as well as reduced nonphosphorylated neurofilament expression in V1. These results reveal that the Crx mutation and lack of light stimulation through the photoreceptor pathway regulate the development and phenotype of different neuronal populations in V1 but not its general morphology. We conclude, therefore, that photoreceptor-mediated visual input during development is crucial for the normal postnatal development and maturation of subsets of cortical neurons. PMID: 20034544 [PubMed - as supplied by publisher] | | | 
|
No comments:
Post a Comment