Fiber‐post bond strength in canals obturated with a cross‐linked gutta‐percha core obturator

The aim of this in‐vitro study was to evaluate the bond strength of fiber posts cemented in a root canal filled using various root‐canal obturation techniques. A total of 33 monoradicular samples, treated endodontically, were randomly assigned to three groups according to the root‐canal obturation technique: group 1, continuous‐wave technique; group 2, plastic‐obturator‐core technique; and group 3, cross‐linked gutta‐percha obturator‐core technique. Fiber posts were luted in each sample and each was sectioned perpendicular to the post axis. The push‐out test was performed using a universal machine and the maximum failure load was recorded in MPa mm^?2. Several samples were randomly chosen for scanning electron microscopy evaluation. The mean debris and dentinal tubule‐opening scores were calculated separately in the coronal and apical portions. Bond strength was significantly higher in group 1 than in groups 2 and 3. Debris scores were significantly higher in the apical portion of groups 2 and 3 than in group 1. Within the limitations of this study it can be affirmed that thermoplasticized alpha gutta‐percha seemed to worsen the cleaning of post‐space walls and hence reduced fiber‐post bond strength.     

Vertiginous crisis following temporomandibular joint athrocentesis: a case report

Temporomandibular joint arthrocentesis and arthroscopy have recently exceeded open surgeries for disorders that failed to respond to conservative treatment. The efficacy of arthrocentesis in reestablishing normal mouth opening and reducing pain and dysfunctions is now commonly accepted, but in contrast to arthroscopy, there are no large series studies on arthrocentesis complications. We report the major complication occurred in our experience: a case of a patient that complained of a violent vertigo, without hearing disorders, following the procedure.     

Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition, cytotoxic drugs, and gamma-irradiation.

Integrin-mediated cellular adhesion to extracellular matrix (ECM) components is an important determinant of chemotherapeutic response of human myeloma cells. Here, we demonstrate that when K562 chronic myelogenous leukemia (CML) cells are adhered to fibronectin (FN), they become resistant to apoptosis induced by the BCR/ABL inhibitors AG957 and STI-571, as well as DNA damaging agents and gamma-irradiation. This phenomenon, termed cell adhesion-mediated drug resistance (CAM-DR), was induced by adhesion through the alpha5beta1 (VLA-5) integrin. Phosphotyrosine analysis demonstrates that anti-apoptotic signaling through integrins in K562 cells is independent of the tyrosine kinases activated by BCR/ABL, with the possible exception of an unknown 80 kDa protein. Cytoprotection of FN-adhered CML cells indicates that tumor-ECM interactions may be critical for the emergence of drug-resistant tumor populations and treatment failure in this disease. Antagonists of beta1 integrin-mediated adhesion or corresponding signal transduction elements may sensitize CML cells to chemotherapy and prevent resistance to the novel BCR/ABL kinase inhibitors being used for the treatment of this disease.     

Combined blockade of protein kinase A and bcl-2 by antisense strategy induces apoptosis and inhibits tumor growth and angiogenesis.

Protein kinase A type I (PKAI) plays a key role in neoplastic transformation, conveys mitogenic signals from different sources, and is overexpressed in the majority of human tumors. Inhibition of PKAI by different tools results in cancer-cell growth inhibition in vitro and in vivo. We and others have recently shown that a novel class of mixed-backbone oligonucleotides targeting the PKAI subunit RIalpha exhibits improved pharmacokinetic properties and antitumor activity accompanied by increased apoptosis in several human cancer types in vitro and in vivo. The role of bcl-2 in the control of apoptosis has been widely documented, and the inhibition of bcl-2 expression and function may have important therapeutic implications. In fact, oligonucleotides antisense bcl-2 have shown antitumor activity in animal models and have successfully completed early clinical trials. Recent studies have demonstrated a direct role of PKA in the regulation of the bcl-2-dependent apoptotic pathway. Therefore, we have investigated the combined blockade of PKA and bcl-2 by antisense strategy as a potential therapeutic approach. The novel hybrid DNA/RNA mixed-backbone oligonucleotide antisense RIalpha (AS RIalpha) in combination with the antisense bcl-2 (AS bcl-2), cooperatively inhibited bcl-2 expression and soft agar growth and induced apoptosis in different human cancer cell lines. p.o. administration of AS RIalpha in combination with i.p. AS bcl-2 caused a marked antitumor effect and a significant prolongation of survival in nude mice bearing human colon cancer xenografts. Moreover, histochemical analysis of tumor specimens showed inhibition of RIalpha and Ki67 expression, inhibition of angiogenesis, and parallel induction of apoptosis in vivo. The results of our study imply an interaction between the PKA and bcl-2 signaling pathways and, because both antisenses have now entered Phase II trials, provide the rationale to translate this novel therapeutic strategy in a clinical setting.