Cardiomyocyte Specific Ablation of p53 Is Not Sufficient to Block Doxorubicin Induced Cardiac Fibrosis and Associated Cytoskeletal Changes

Doxorubicin (Dox) is an anthracycline used to effectively treat several forms of cancer. Unfortunately, the use of Dox is limited due to its association with cardiovascular complications which are manifested as acute and chronic cardiotoxicity. The pathophysiological mechanism of Dox induced cardiotoxicity appears to involve increased expression of the tumor suppressor protein p53 in cardiomyocytes, followed by cellular apoptosis. It is not known whether downregulation of p53 expression in cardiomyocytes would result in decreased rates of myocardial fibrosis which occurs in response to cardiomyocyte loss. Further, it is not known whether Dox can induce perivascular necrosis and associated fibrosis in the heart. In this study we measured the effects of acute Dox treatment on myocardial and perivascular apoptosis and fibrosis in a conditional knockout (CKO) mouse model system which harbours inactive p53 alleles specifically in cardiomyocytes. CKO mice treated with a single dose of Dox (20 mg/kg), did not display lower levels of myocardial apoptosis or reactive oxygen and nitrogen species (ROS/RNS) compared to control mice with intact p53 alleles. Interestingly, CKO mice also displayed higher levels of interstitial and perivascular fibrosis compared to controls 3 or 7 days after Dox treatment. Additionally, the decrease in levels of the microtubule protein α-tubulin, which occurs in response to Dox treatment, was not prevented in CKO mice. Overall, these results indicate that selective loss of p53 in cardiomyocytes is not sufficient to prevent Dox induced myocardial ROS/RNS generation, apoptosis, interstitial fibrosis and perivascular fibrosis. Further, these results support a role for p53 independent apoptotic pathways leading to Dox induced myocardial damage and highlight the importance of vascular lesions in Dox induced cardiotoxicity

Plasma cell myeloma: management of a mandibular fracture.

An interesting case of kappa light-chain plasma cell myeloma with pathologic mandibular fracture is presented. Traditional fracture management techniques were abandoned in view of the advanced state of this patient\u27s disease. With the use of adjunctive radiotherapy and a soft diet, clinical union of the fractured mandible was achieved without immobilization

Alveolar pyogenic granuloma: review and report of a case.

A large exophytic bone-resorbing lesion was discovered in the oral cavity of an institutionalized 33-year-old male. An excisional biopsy under general anesthesia was performed. Frozen and permanent histologic sections confirmed a reactive gingival fibroma consistent with a pyogenic granuloma. This lesion is unusual in that it attained a very large size and caused marked remodeling of the alveolar bone of the mandible. Of interest as well, this highly vascular lesion was found to have numerous feeding vessels from the alveolar bone. A retained tooth root was encountered within the lesion, presumably the etiologic factor producing this lesion. A differential diagnosis is presented and discussed. The lesion should be of particular interest to otolaryngologists who deal with intraoral lesions and their treatment, since it illustrates an extreme presentation of a totally benign process

Postinjection infection-two unusual cases.

Two unusual forms of infection after local anesthesia have been presented. The first, a case of cellulitis, was thought initially to be a hypersensitivity reaction. The second, a case of impetigo, might prove difficult to diagnose because of its relative rarity

Cystic complex composite odontoma. Report of two cases.

The two cases presented here involved complex composite odontomas that had become cystic. They were very different in appearance; the first case being almost classic and the second case showing more bizarre configuration and being associated with a much larger cystic cavity. Two different surgical approaches were used. In the first case a bone graft from the iliac crest was used to fill the extensive mandibular defect. In the second case, enucleation with good primary closure was thought to be sufficient since good bony margins were evident and the likelihood of pathologic fracture was considered minimal

Osteoradionecrosis of maxillae.

A case of osteoradionecrosis of the maxilla has been presented. It is hoped that this review and discussion of osteomyelitis and osteoradionecrosis will point out the need for proper management of the dentition of cancer patients who are subjected to radiotherapy

Alloplastic reconstruction of the temporomandibular joint.

The Proplast TMJ condylar implant, the glenoid fossa implant, and the TMJ interpositional implants should be singled out as having provided a new and more predictable mode of TMJ reconstruction. The use of these implants in cases of ankylosis, degenerative joint disease, orthognathic deformities, and traumatic injuries has greatly contributed to the success of these reconstructions. These implants represent the state of the art in TMJ reconstruction and increasing data from longer-term follow-up have shown a rate of success much higher than any previous implant used in the TMJ. TMJ reconstruction requires careful surgical planning, meticulous surgical technique, and intelligent perioperative care. Postoperative physical therapy is considered essential in the management of these patients. Complications related to reankylosis have been virtually eliminated, as no postoperative immobilization is required in most cases. Long-term stability of these implants, due to the ingrowth of tissue into Proplast, appears to be assured. Continued experience with the implants and close follow-up of reconstruction patients is necessary in the future to adequately assess the performance of the newer glenoid fossa and TMJ interpositional implants. Certainly, a new era in TMJ reconstruction has begun, resulting in increased benefits to the patients whom we all serve