Dichloroacetate-induced modulation of cellular antioxidant enzyme activities and glutathione level in the J774A.1 cells

Dichloroacetate (DCA) is used for different medical and industrial purposes and has been found to be a toxic by-product produced during the process of water chlorination. The DCA effects on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) level were assessed and correlated with each other and also with cellular viabilities in J774A.1 macrophage cells. A concentration of 24 mm of DCA resulted in time-dependent decreases in cellular viability and glutathione level, and time-dependent increases in SOD activity when incubated with the cells for 24-48 h. DCA also resulted in significant increases in CAT and GSH-Px activities of the viable cells when incubated with the cells for 36 and 48 h. The changes in antioxidant enzyme activities and GSH levels were found to be strongly correlated with each other, and with cellular viabilities at different time points. While GSH did not result in any significant effects when added to the cells at concentrations ranging between 15 and 60 nmol ml(-1), it resulted in concentration-dependent increases in cellular viability when added to the DCA-treated cells, with maximal effects achieved at 45-60 nmol GSH ml(-1). However, cellular viability of the GSH + DCA treated cells remained below that of the control. Since viable cells from the DCA-treated cultures displayed significantly higher antioxidant enzyme activities compared with the control, it is concluded that those increases may have contributed to the cellular protection against DCA-induced cell death. Also, glutathione depletion has a major contribution to the observed cellular death induced by DCA.     

Innovation in care for individuals with cognitive impairment: Can reimbursement policy spread best practices?

There is now an unprecedented opportunity to improve the care of the over 5 million people who are living with Alzheimer's disease and related dementias and many more with cognitive impairment due to brain injury, systemic diseases, and other causes. The introduction of a new Medicare care planning benefit—long sought openly by advocacy organizations and clinicians and badly needed by patients and families—could greatly improve health care quality, but only if widely and fully implemented. We describe the components of this new benefit and its promise of better clinical care, as well as its potential to create a new platform for clinical and health outcomes research. We highlight external factors—and some that are internal to the benefit structure itself—that challenge the full realization of its value, and we call for broad public and professional engagement to ensure that it will not fail.     

IgM myeloma: A multicenter retrospective study of 134 patients

IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL^?1 with 19% of patients presenting with levels >6,000 mg dL^?1. International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t (11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.     

Solitary plasmacytomas: outcome and prognostic factors after definitive radiation therapy

BACKGROUND:

The objective of this study was to review the outcome of patients with solitary plasmacytoma (SP) after definitive radiation therapy.

METHODS:

The authors retrospectively reviewed 84 patients with SP who were diagnosed and treated at The University of Texas MD Anderson Cancer Center during 1988 to 2008. The impact of tumor anatomic site, tumor size, and the presence of serum and urinary paraprotein at diagnosis was assessed on local control, survival, and the risk of developing multiple myeloma (MM).

RESULTS:

Fifty‐nine patients (70%) had bone SP, and 25 patients (30%) had extramedullary SP. Serum paraprotein was present in 39 patients (46%). The median radiation dose was 45 grays (Gy) (range, 36‐53.4 Gy). Local control was achieved in 77 patients (92%). Neither radiation dose nor tumor size predicted local control. The 5‐year rate of progression to MM was 47% and was higher for patients with bone SP (56% vs 30% for extramedullary SP; P = .021), and patients who had serum paraprotein detected at diagnosis (60% vs 39%; P = .016). On univariate analysis, patients aged <60 years and men had higher rates of progression to MM, although the differences were not significant (P = .048 and P = .29, respectively). Multivariate analysis revealed that bone location and serum protein at diagnosis were associated statistically with progression to MM. The 5‐year overall survival rate for the entire patient cohort was 78%, and no difference was observed between patients who had bone SP versus extramedullary SP (76% vs 85%, respectively; P = .274).

CONCLUSIONS:

The current results indicated that definitive radiation therapy for SP can provide excellent local control. Progression to MM remains the main problem and is more common among patients with bone SP and those who have serum paraprotein detected at diagnosis. Cancer 2011;. © 2011 American Cancer Society.     

Influence of Implant Surface Topography and Loading Condition on Stress Distribution in Bone Around Implants: A Comparative 3D FEA

A three-dimensional Finite Element Method was used to study the influence of porous coated surface topography of an implant on stress and strain distribution pattern in the cortical and cancellous bone during axial and non-axial loading. Two implants, one with porous surface topography and one with smooth surface were embedded in separate geometric models of posterior mandibular region which was generated using a CT scan data. Material properties and boundary conditions were applied. Load of 100 and 50 N were applied on to the abutment from axial and non-axial directions respectively. Porous surface topography appeared to distribute stress in a more uniform pattern around the implant with near absence of stress in the apical region of implant. Smooth surfaced implant showed high punching stress at the apex of the implant. The porous coated interface was considered to simulate the shock absorbing behavior of periodontal ligament of natural dentition. Maximum amount of stress concentration was observed in the cortical bone which plays a major role in the dissipation of the stress.